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Sample records for breast tumours identifies

  1. Breast tumours of adolescents in an African population

    Directory of Open Access Journals (Sweden)

    Umanah Ivy

    2010-01-01

    Full Text Available Background: Tumours of the breast are uncommon in childhood and adolescence. Patients in this age group often require a different approach to diagnosis and treatment. The purpose of this study is to highlight the clinicopathologic features of breast tumours in adolescents in a Nigerian city. Materials and Methods: Eighty-four breast tumour materials from patients aged 10-19 years were analyzed over a 10-year period at the Department of Pathology, University of Benin Teaching Hospital (UBTH, Benin City, Edo State, Benin City, Nigeria. Results: A majority of the breast tumours were benign. Fibroadenoma was the most common tumour with 46 cases (54.8%, followed by fibrocystic changes with 15 cases (17%. Malignancy was extremely rare in this group, with only one case (1.2% of an invasive ductal carcinoma. Histologically, most tumours were indistinguishable from the adult types. Conclusion: Fibroadenoma is the most common breast tumour in adolescents in Benin City, Nigeria. Breast cancer and male breast tumours are rare in this age group. Routine complete physical examination of children and adolescents should include breast examination.

  2. Tumour location within the breast: Does tumour site have prognostic ability?

    Science.gov (United States)

    Rummel, Seth; Hueman, Matthew T; Costantino, Nick; Shriver, Craig D; Ellsworth, Rachel E

    2015-01-01

    Tumour location within the breast varies with the highest frequency in the upper outer quadrant (UOQ) and lowest frequency in the lower inner quadrant (LIQ). Whether tumour location is prognostic is unclear. To determine whether tumour location is prognostic, associations between tumour site and clinicopathological characteristics were evaluated. All patients enrolled in the Clinical Breast Care Project whose tumour site-UOQ, upper inner quadrant (UIQ), central, LIQ, lower outer quadrant (LOQ)-was determined by a single, dedicated breast pathologist were included in this study. Patients with multicentric disease (n = 122) or tumours spanning multiple quadrants (n = 381) were excluded from further analysis. Clinicopathological characteristics were analysed using chi-square tests for univariate analysis with multivariate analysis performed using principal components analysis (PCA) and multiple logistic regression. Significance was defined as P location, 30 had bilateral disease. Tumour location in the UOQ (51.5%) was significantly higher than in the UIQ (15.6%), LOQ (14.2%), central (10.6%), or LIQ (8.1%). Tumours in the central quadrant were significantly more likely to have higher tumour stage (P = 0.003) and size (P location as a prognostic factor revealed that although tumours in the central region are associated with less favourable outcome, these associations are not independent of location but rather driven by larger tumour size. Tumours in the central region are more difficult to detect mammographically, resulting in larger tumour size at diagnosis and thus less favourable prognosis. Together, these data demonstrate that tumour location is not an independent prognostic factor.

  3. Oxidative stress specifically downregulates survivin to promote breast tumour formation.

    Science.gov (United States)

    Pervin, S; Tran, L; Urman, R; Braga, M; Parveen, M; Li, S A; Chaudhuri, G; Singh, R

    2013-03-05

    Breast cancer, a heterogeneous disease has been broadly classified into oestrogen receptor positive (ER+) or oestrogen receptor negative (ER-) tumour types. Each of these tumours is dependent on specific signalling pathways for their progression. While high levels of survivin, an anti-apoptotic protein, increases aggressive behaviour in ER- breast tumours, oxidative stress (OS) promotes the progression of ER+ breast tumours. Mechanisms and molecular targets by which OS promotes tumourigenesis remain poorly understood. DETA-NONOate, a nitric oxide (NO)-donor induces OS in breast cancer cell lines by early re-localisation and downregulation of cellular survivin. Using in vivo models of HMLE(HRAS) xenografts and E2-induced breast tumours in ACI rats, we demonstrate that high OS downregulates survivin during initiation of tumourigenesis. Overexpression of survivin in HMLE(HRAS) cells led to a significant delay in tumour initiation and tumour volume in nude mice. This inverse relationship between survivin and OS was also observed in ER+ human breast tumours. We also demonstrate an upregulation of NADPH oxidase-1 (NOX1) and its activating protein p67, which are novel markers of OS in E2-induced tumours in ACI rats and as well as in ER+ human breast tumours. Our data, therefore, suggest that downregulation of survivin could be an important early event by which OS initiates breast tumour formation.

  4. Primary extraskeletal Ewing's sarcoma/primitive neuroectodermal tumour of breast

    OpenAIRE

    Ikhwan, S M; Kenneth, V K T; Seoparjoo, A; Zin, A A M

    2013-01-01

    Primary primitive neuroectodermal tumour (PNET) and extraskeletal Ewing's sarcoma belongs to the Ewing's family of tumours. Primary tumours arising from breast are very rare. There are only a few case reports published on primary extraskeletal Ewing's sarcoma and PNET arising from breast. We present an extremely rare case of an inoperable primary Ewing's sarcoma arising from left breast with contralateral breast, lymphatic and lung metastasis.

  5. Primary extraskeletal Ewing's sarcoma/primitive neuroectodermal tumour of breast.

    Science.gov (United States)

    Ikhwan, S M; Kenneth, V K T; Seoparjoo, A; Zin, A A M

    2013-06-21

    Primary primitive neuroectodermal tumour (PNET) and extraskeletal Ewing's sarcoma belongs to the Ewing's family of tumours. Primary tumours arising from breast are very rare. There are only a few case reports published on primary extraskeletal Ewing's sarcoma and PNET arising from breast. We present an extremely rare case of an inoperable primary Ewing's sarcoma arising from left breast with contralateral breast, lymphatic and lung metastasis.

  6. Histopathological review of breast tumours in children and ...

    African Journals Online (AJOL)

    ... of all tumours followed by tubular adenoma (n = 11; 8.2%) and adenosis (n = 10; 7.4%). No case of malignancy was recorded in this study. Conclusion: Fibroadenoma is the most common breast tumour in children and adolescents in our environment. Key words: Adolescents, breast tumours, childhood, fi broadenoma ...

  7. Recurrence and mortality according to Estrogen Receptor status for breast cancer patients undergoing conservative surgery. Ipsilateral breast tumour recurrence dynamics provides clues for tumour biology within the residual breast

    International Nuclear Information System (INIS)

    Demicheli, Romano; Ardoino, Ilaria; Boracchi, Patrizia; Coradini, Danila; Agresti, Roberto; Ferraris, Cristina; Gennaro, Massimiliano; Hrushesky, William JM; Biganzoli, Elia

    2010-01-01

    the study was designed to determine how tumour hormone receptor status affects the subsequent pattern over time (dynamics) of breast cancer recurrence and death following conservative primary breast cancer resection. Time span from primary resection until both first recurrence and death were considered among 2825 patients undergoing conservative surgery with or without breast radiotherapy. The hazard rates for ipsilateral breast tumour recurrence (IBTR), distant metastasis (DM) and mortality throughout 10 years of follow-up were assessed. DM dynamics displays the same bimodal pattern (first early peak at about 24 months, second late peak at the sixth-seventh year) for both estrogen receptor (ER) positive (P) and negative (N) tumours and for all local treatments and metastatic sites. The hazard rates for IBTR maintain the bimodal pattern for ERP and ERN tumours; however, each IBTR recurrence peak for ERP tumours is delayed in comparison to the corresponding timing of recurrence peaks for ERN tumours. Mortality dynamics is markedly different for ERP and ERN tumours with more early deaths among patients with ERN than among patients with ERP primary tumours. DM dynamics is not influenced by the extent of conservative primary tumour resection and is similar for both ER phenotypes across different metastatic sites, suggesting similar mechanisms for tumour development at distant sites despite apparently different microenvironments. The IBTR risk peak delay observed in ERP tumours is an exception to the common recurrence risk rhythm. This suggests that the microenvironment within the residual breast tissue may enforce more stringent constraints upon ERP breast tumour cell growth than other tissues, prolonging the latency of IBTR. This local environment is, however, apparently less constraining to ERN cells, as IBTR dynamics is similar to the corresponding recurrence dynamics among other distant tissues

  8. The retinoblastoma gene is frequently altered leading to loss of expression in primary breast tumours.

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    Varley, J M; Armour, J; Swallow, J E; Jeffreys, A J; Ponder, B A; T'Ang, A; Fung, Y K; Brammar, W J; Walker, R A

    1989-06-01

    We have analysed the organisation of the retinoblastoma (RB1) gene in 77 primary breast carcinomas, in metastatic tissue derived from 16 of those primary tumours, and in a variety of benign breast lesions. Expression of RB1 was also assessed in most samples by immunohistochemical detection of the RB1 protein in tissue sections. Structural abnormalities to RB1 were detected in DNA from 15/77 (19%) of primary breast carcinomas examined. Where DNA was available from metastatic tissue derived from such primary tumours, the same aberration could be detected. No alterations were seen in benign breast lesions. 16/56 (29%) of tumours examined for expression by immunohistochemical methods showed a proportion of tumour cells to be completely negative for the RB1 protein. All tumours in which a structural alteration to RB1 was detected had a proportion of negative cells, except for one case where all cells were positive. Several primary tumour samples were identified where there was no detectable structural change to the gene, but there was loss of expression in some tumour cells. The data presented here demonstrate that changes to the RB1 gene leading to loss of expression of both alleles are frequent in primary human breast tumours.

  9. Tumour-associated endothelial-FAK correlated with molecular sub-type and prognostic factors in invasive breast cancer

    International Nuclear Information System (INIS)

    Alexopoulou, Annika N; Ho-Yen, Colan M; Papalazarou, Vassilis; Elia, George; Jones, J Louise; Hodivala-Dilke, Kairbaan

    2014-01-01

    Breast cancer is a heterogeneous disease that can be classified into one of 4 main molecular sub-types: luminal A, luminal B, Her2 over-expressing and basal-like (BL). These tumour sub-types require different treatments and have different risks of disease progression. BL cancers can be considered a sub-group of Triple negative (TN) cancers since they lack estrogen (ER), progesterone (PR) and Her2 expression. No targeted treatment currently exists for TN/BL cancers. Thus it is important to identify potential therapeutic targets and describe their relationship with established prognostic factors. Focal adhesion kinase (FAK) is upregulated in several human cancers and also plays a functional role in tumour angiogenesis. However, the association between breast cancer sub-types and tumour endothelial-FAK expression is unknown. Using immunofluorescence, we quantified FAK expression in tumour endothelial and tumour cell compartments in 149 invasive breast carcinomas and correlated expression with clinical, pathological and molecular parameters. Low endothelial-FAK expression was independently associated with luminal A tumours at univariate (p < 0.001) and multivariate (p = 0.001) analysis. There was a positive correlation between FAK expression in the vascular and tumour cell compartments (Spearman’s correlation co-efficient = 0.394, p < 0.001). Additionally, endothelial and tumour cell FAK expression were significantly increased in TN tumours (p = 0.043 and p = 0.033 respectively), in tumours with negative ER and PR status, and in high grade tumours at univariate analysis. Our findings establish a relationship between endothelial-FAK expression levels and the molecular sub-type of invasive breast cancer, and suggest that endothelial-FAK expression is potentially more clinically relevant than tumour cell FAK expression in breast cancer

  10. Preoperative estimation of the pathological breast tumour size by physical examination, mammography and ultrasound: a prospective study on 105 invasive tumours

    International Nuclear Information System (INIS)

    Bosch, Anne M.; Kessels, Alfons G.H.; Beets, Geerard L.; Rupa, Jan D.; Koster, Dick; Engelshoven, Jos M.A. van; Meyenfeldt, Maarten F. von

    2003-01-01

    Objective: The clinical breast tumour size can be assessed preoperatively by physical examination, mammography and ultrasound. At present it is not clear which modality correlates best with the histological invasive breast tumour size. This prospective study aims to determine the most accurate clinical method (physical examination, mammography or ultrasound) to predict the histological invasive tumour size preoperatively. Methods and patients: Between October 1999 and August 2000, 96 women with 105 invasive malignant breast tumours were included in this study. All patients underwent excision and the tumour size was measured on histology. Tumour size was measured by all three modalities in 73 cases. Results were evaluated by calculating correlation coefficients. The examination modalities presenting the best estimation of the pathological tumour size were used in a stepwise linear regression analysis to construct a formula predicting the pathological tumour size from the result of the various diagnostic modalities. Results: The correlation coefficient between ultrasound and pathological size (r=0.68) was significantly better than the correlations between physical examination and pathological size (r=0.42) and mammographic and pathological size (r=0.44). Physical examination overestimates and ultrasound underestimates breast tumour classification. The most accurate prediction formula was: Pathological tumour size (mm) equals sonographic tumour size (mm)+3 mm. Conclusion: When comparing physical examination, mammography and ultrasound for the prediction of the pathological size of a malignant breast tumour, ultrasound is the best predictor. The ensuing regression formula determines pathological size as tumour size by ultrasound+3 mm. However, with the wide 95% confidence interval of ±11 mm, it remains difficult to predict the exact pathological size for an individual invasive breast tumour. A small deviation in millimetres of the tumour size could lead to a change in

  11. Diffusion-weighted imaging features of breast tumours and the surrounding stroma reflect intrinsic heterogeneous characteristics of molecular subtypes in breast cancer

    KAUST Repository

    Fan, Ming; He, Ting; Zhang, Peng; Cheng, Hu; Zhang, Juan; Gao, Xin; Li, Lihua

    2017-01-01

    Breast cancer heterogeneity is the main obstacle preventing the identification of patients with breast cancer with poor prognoses and treatment responses; however, such heterogeneity has not been well characterized. The purpose of this retrospective study was to reveal heterogeneous patterns in the apparent diffusion coefficient (ADC) signals in tumours and the surrounding stroma to predict molecular subtypes of breast cancer. A dataset of 126 patients with breast cancer, who underwent preoperative diffusion-weighted imaging (DWI) on a 3.0-T image system, was collected. Breast images were segmented into regions comprising the tumour and surrounding stromal shells in which features that reflect heterogeneous ADC signal distribution were extracted. For each region, imaging features were computed, including the mean, minimum, variance, interquartile range (IQR), range, skewness, kurtosis and entropy of ADC values. Univariate and stepwise multivariate logistic regression modelling was performed to identify the magnetic resonance imaging features that optimally discriminate luminal A, luminal B, human epidermal growth factor 2 (HER2)-enriched and basal-like molecular subtypes. The performance of the predictive models was evaluated using the area under the receiver operating characteristic curve (AUC). Univariate logistic regression analysis showed that the skewness in the tumour boundary achieved an AUC of 0.718 for discrimination between luminal A and non-luminal A tumours, whereas the IQR of the ADC value in the tumour boundary had an AUC of 0.703 for classification of the HER2-enriched subtype. Imaging features in the tumour boundary and the proximal peritumoral stroma corresponded to a higher overall prediction performance than those in other regions. A multivariate logistic regression model combining features in all the regions achieved an overall AUC of 0.800 for the classification of the four tumour subtypes. These findings suggest that features in the tumour

  12. Diffusion-weighted imaging features of breast tumours and the surrounding stroma reflect intrinsic heterogeneous characteristics of molecular subtypes in breast cancer

    KAUST Repository

    Fan, Ming

    2017-12-16

    Breast cancer heterogeneity is the main obstacle preventing the identification of patients with breast cancer with poor prognoses and treatment responses; however, such heterogeneity has not been well characterized. The purpose of this retrospective study was to reveal heterogeneous patterns in the apparent diffusion coefficient (ADC) signals in tumours and the surrounding stroma to predict molecular subtypes of breast cancer. A dataset of 126 patients with breast cancer, who underwent preoperative diffusion-weighted imaging (DWI) on a 3.0-T image system, was collected. Breast images were segmented into regions comprising the tumour and surrounding stromal shells in which features that reflect heterogeneous ADC signal distribution were extracted. For each region, imaging features were computed, including the mean, minimum, variance, interquartile range (IQR), range, skewness, kurtosis and entropy of ADC values. Univariate and stepwise multivariate logistic regression modelling was performed to identify the magnetic resonance imaging features that optimally discriminate luminal A, luminal B, human epidermal growth factor 2 (HER2)-enriched and basal-like molecular subtypes. The performance of the predictive models was evaluated using the area under the receiver operating characteristic curve (AUC). Univariate logistic regression analysis showed that the skewness in the tumour boundary achieved an AUC of 0.718 for discrimination between luminal A and non-luminal A tumours, whereas the IQR of the ADC value in the tumour boundary had an AUC of 0.703 for classification of the HER2-enriched subtype. Imaging features in the tumour boundary and the proximal peritumoral stroma corresponded to a higher overall prediction performance than those in other regions. A multivariate logistic regression model combining features in all the regions achieved an overall AUC of 0.800 for the classification of the four tumour subtypes. These findings suggest that features in the tumour

  13. Strain histograms are equal to strain ratios in predicting malignancy in breast tumours

    DEFF Research Database (Denmark)

    Carlsen, Jonathan Frederik; Ewertsen, Caroline; Sletting, Susanne

    2017-01-01

    Objectives: To assess whether strain histograms are equal to strain ratios in predicting breast tumour malignancy and to see if either could be used to upgrade Breast Imaging Reporting and Data System (BI-RADS) 3 tumours for immediate biopsy. Methods: Ninety-nine breast tumours were examined using...

  14. Surveillance mammography for detecting ipsilateral breast tumour recurrence and metachronous contralateral breast cancer: a systematic review

    Energy Technology Data Exchange (ETDEWEB)

    Robertson, Clare; Boachie, Charles; Fraser, Cynthia; MacLennan, Graeme; Mowatt, Graham; Thomas, Ruth E. [University of Aberdeen, Health Services Research Unit, Aberdeen (United Kingdom); Ragupathy, Senthil Kumar Arcot [NHS Grampian, Radiology Department, Aberdeen Royal Infirmary, Aberdeen (United Kingdom); Heys, Steve D. [University of Aberdeen and Aberdeen Royal Infirmary, NHS Grampian, Division of Applied Medicine, School of Medicine and Dentistry, Aberdeen (United Kingdom); Gilbert, Fiona J. [University of Aberdeen and Aberdeen Royal Infirmary, NHS Grampian, Aberdeen Biomedical Imaging Centre, Aberdeen (United Kingdom)

    2011-12-15

    To determine the diagnostic accuracy of surveillance mammography for detecting ipsilateral breast tumour recurrence and metachronous contralateral breast cancer in women previously treated for primary breast cancer. A systematic review of surveillance mammography compared with ultrasound, magnetic resonance imaging (MRI), specialist-led clinical examination or unstructured primary care follow-up, using histopathological assessment for test positives and follow-up for test negatives as the reference standard. Nine studies met our inclusion criteria. Variations in study comparisons precluded meta-analysis. For routine ipsilateral breast tumour detection, surveillance mammography sensitivity ranged from 64-67% and specificity ranged from 85-97%. For MRI, sensitivity ranged from 86-100% and specificity was 93%. For non-routine ipsilateral breast tumour detection, sensitivity and specificity for surveillance mammography ranged from 50-83% and 57-75% and for MRI 93-100% and 88-96%. For routine metachronous contralateral breast cancer detection, one study reported sensitivity of 67% and specificity of 50% for both surveillance mammography and MRI. Although mammography is associated with high sensitivity and specificity, MRI is the most accurate test for detecting ipsilateral breast tumour recurrence and metachronous contralateral breast cancer in women previously treated for primary breast cancer. Results should be interpreted with caution because of the limited evidence base. (orig.)

  15. Morphology and genomic hallmarks of breast tumours developed by ATM deleterious variant carriers.

    Science.gov (United States)

    Renault, Anne-Laure; Mebirouk, Noura; Fuhrmann, Laetitia; Bataillon, Guillaume; Cavaciuti, Eve; Le Gal, Dorothée; Girard, Elodie; Popova, Tatiana; La Rosa, Philippe; Beauvallet, Juana; Eon-Marchais, Séverine; Dondon, Marie-Gabrielle; d'Enghien, Catherine Dubois; Laugé, Anthony; Chemlali, Walid; Raynal, Virginie; Labbé, Martine; Bièche, Ivan; Baulande, Sylvain; Bay, Jacques-Olivier; Berthet, Pascaline; Caron, Olivier; Buecher, Bruno; Faivre, Laurence; Fresnay, Marc; Gauthier-Villars, Marion; Gesta, Paul; Janin, Nicolas; Lejeune, Sophie; Maugard, Christine; Moutton, Sébastien; Venat-Bouvet, Laurence; Zattara, Hélène; Fricker, Jean-Pierre; Gladieff, Laurence; Coupier, Isabelle; Chenevix-Trench, Georgia; Hall, Janet; Vincent-Salomon, Anne; Stoppa-Lyonnet, Dominique; Andrieu, Nadine; Lesueur, Fabienne

    2018-04-17

    characteristics and genomic alterations, and they are also distinguishable from sporadic breast tumours, thus opening up the possibility to identify ATM variant carriers outside the ataxia-telangiectasia disorder and direct them towards effective cancer risk management and therapeutic strategies.

  16. Tumour bed boost radiotherapy for women after breast-conserving surgery.

    Science.gov (United States)

    Kindts, Isabelle; Laenen, Annouschka; Depuydt, Tom; Weltens, Caroline

    2017-11-06

    Breast-conserving therapy, involving breast-conserving surgery followed by whole-breast irradiation and optionally a boost to the tumour bed, is a standard therapeutic option for women with early-stage breast cancer. A boost to the tumour bed means that an extra dose of radiation is applied that covers the initial tumour site. The rationale for a boost of radiotherapy to the tumour bed is that (i) local recurrence occurs mostly at the site of the primary tumour because remaining microscopic tumour cells are most likely situated there; and (ii) radiation can eliminate these causative microscopic tumour cells. The boost continues to be used in women at high risk of local recurrence, but is less widely accepted for women at lower risk. Reasons for questioning the boost are twofold. Firstly, the boost brings higher treatment costs. Secondly, the potential adverse events are not negligible. In this Cochrane Review, we investigated the effect of the tumour bed boost on local control and side effects. To assess the effects of tumour bed boost radiotherapy after breast-conserving surgery and whole-breast irradiation for the treatment of breast cancer. We searched the Cochrane Breast Cancer Specialised Register, the Cochrane Central Register of Controlled Trials (CENTRAL), MEDLINE (January 1966 to 1 March 2017), Embase (1980 to 1 March 2017), the World Health Organization International Clinical Trials Registry Platform, and ClinicalTrials.gov on 1 March 2017. We also searched the European Society of Radiotherapy and Oncology Annual Meeting, the St Gallen Oncology Conferences, and the American Society for Radiation Oncology Annual Meeting for abstracts. Randomised controlled trials comparing the addition and the omission of breast cancer tumour bed boost radiotherapy. Two review authors (IK and CW) performed data extraction and assessed risk of bias using Cochrane's 'Risk of bias' tool, resolving any disagreements through discussion. We entered data into Review Manager 5 for

  17. Association of primary tumour FDG uptake with clinical, histopathological and molecular characteristics in breast cancer patients scheduled for neoadjuvant chemotherapy

    Energy Technology Data Exchange (ETDEWEB)

    Koolen, B.B.; Aukema, T.S. [Netherlands Cancer Institute-Antoni van Leeuwenhoek Hospital, Department of Nuclear Medicine, Amsterdam (Netherlands); Netherlands Cancer Institute-Antoni van Leeuwenhoek Hospital, Department of Surgical Oncology, Amsterdam (Netherlands); Vrancken Peeters, M.J.T.F.D.; Rutgers, E.J.T. [Netherlands Cancer Institute-Antoni van Leeuwenhoek Hospital, Department of Surgical Oncology, Amsterdam (Netherlands); Wesseling, J.; Lips, E.H. [Netherlands Cancer Institute-Antoni van Leeuwenhoek Hospital, Department of Pathology and Experimental Therapy, Amsterdam (Netherlands); Vogel, W.V.; Valdes Olmos, R.A. [Netherlands Cancer Institute-Antoni van Leeuwenhoek Hospital, Department of Nuclear Medicine, Amsterdam (Netherlands); Werkhoven, E. van [Netherlands Cancer Institute-Antoni van Leeuwenhoek Hospital, Department of Biometrics, Amsterdam (Netherlands); Gilhuijs, K.G.A. [Netherlands Cancer Institute-Antoni van Leeuwenhoek Hospital, Department of Radiology, Amsterdam (Netherlands); University Medical Centre Utrecht, Department of Radiology, Utrecht (Netherlands); Rodenhuis, S. [Netherlands Cancer Institute-Antoni van Leeuwenhoek Hospital, Department of Medical Oncology, Amsterdam (Netherlands)

    2012-12-15

    The aim of this study was to evaluate the association of primary tumour {sup 18}F-fluorodeoxyglucose (FDG) uptake with clinical, histopathological and molecular characteristics of breast cancer patients scheduled for neoadjuvant chemotherapy. Second, we wished to establish for which patients pretreatment positron emission tomography (PET)/CT could safely be omitted because of low FDG uptake. PET/CT was performed in 214 primary stage II or III breast cancer patients in the prone position with hanging breasts. Tumour FDG uptake was qualitatively evaluated to determine the possibility of response monitoring with PET/CT and was quantitatively assessed using maximum standardized uptake values (SUV{sub max}). FDG uptake was compared with age, TNM stage, histology, hormone and human epidermal growth factor receptor 2 status, grade, Ki-67 and molecular subtype in univariable and multivariable analyses. In 203 tumours (95 %) FDG uptake was considered sufficient for response monitoring. No subgroup of patients with consistently low tumour FDG uptake could be identified. In a univariable analysis, SUV{sub max} was significantly higher in patients with distant metastases at staging examination, non-lobular carcinomas, tumours with negative hormone receptors, triple negative tumours, grade 3 tumours, and in tumours with a high proliferation index (Ki-67 expression). After multiple linear regression analysis, triple negative and grade 3 tumours were significantly associated with a higher SUV{sub max}. Primary tumour FDG uptake in breast cancer patients scheduled for neoadjuvant chemotherapy is significantly higher in tumours with prognostically unfavourable characteristics. Based on tumour characteristics associated with low tumour FDG uptake, this study was unable to identify a subgroup of patients unlikely to benefit from pretreatment PET/CT. (orig.)

  18. Measurement of tumour size with mammography, sonography and magnetic resonance imaging as compared to histological tumour size in primary breast cancer

    International Nuclear Information System (INIS)

    Gruber, Ines V; Rueckert, Miriam; Kagan, Karl O; Staebler, Annette; Siegmann, Katja C; Hartkopf, Andreas; Wallwiener, Diethelm; Hahn, Markus

    2013-01-01

    Tumour size in breast cancer influences therapeutic decisions. The purpose of this study was to evaluate sizing of primary breast cancer using mammography, sonography and magnetic resonance imaging (MRI) and thereby establish which imaging method most accurately corresponds with the size of the histological result. Data from 121 patients with primary breast cancer were analysed in a retrospective study. The results were divided into the groups “ductal carcinoma in situ (DCIS)”, invasive ductal carcinoma (IDC) + ductal carcinoma in situ (DCIS)”, “invasive ductal carcinoma (IDC)”, “invasive lobular carcinoma (ILC)” and “other tumours” (tubular, medullary, mucinous and papillary breast cancer). The largest tumour diameter was chosen as the sizing reference in each case. Bland-Altman analysis was used to determine to what extent the imaging tumour size correlated with the histopathological tumour sizes. Tumour size was found to be significantly underestimated with sonography, especially for the tumour groups IDC + DCIS, IDC and ILC. The greatest difference between sonographic sizing and actual histological tumour size was found with invasive lobular breast cancer. There was no significant difference between mammographic and histological sizing. MRI overestimated non-significantly the tumour size and is superior to the other imaging techniques in sizing of IDC + DCIS and ILC. The histological subtype should be included in imaging interpretation for planning surgery in order to estimate the histological tumour size as accurately as possible

  19. Adenomyoepithelial tumours and myoepithelial carcinomas of the breast – a spectrum of monophasic and biphasic tumours dominated by immature myoepithelial cells

    Directory of Open Access Journals (Sweden)

    Herbst Hermann

    2005-07-01

    Full Text Available Abstract Background Adenomyoepithelial tumours and myoepithelial carcinomas of the breast are primarily defined by the presence of neoplastic cells with a myoepithelial immunophenotype. Current classification schemes are based on purely descriptive features and an assessment of individual prognosis is still problematic. Methods A series of 27 adenomyoepithelial tumours of the breast was analysed immunohistochemically with antibodies directed against various cytokeratins, p63, smooth muscle alpha-actin (SMA and vimentin. Additionally, double immunofluorescence and comparative genomic hybridisation (CGH was performed. Results Immunohistochemically, all the tumours showed a constant expression of high molecular weight cytokeratins (Ck Ck5 and Ck14, p63, SMA and vimentin. With exception of one case diagnosed as myoepithelial carcinoma, all tested tumours expressed low molecular weight cytokeratin Ck18 in variable proportions of cells. Even in monophasic tumours lacking obvious glandular differentiation in conventional staining, a number of neoplastic cells still expressed those cytokeratins. Double immunofluorescence revealed tumour cells exclusively staining for Ck5/Ck14 in the presence of other cell populations that co-expressed high molecular weight Ck5/Ck14 as well as either low molecular weight Ck8/18 or SMA. Based on morphology, we assigned the series to three categories, benign, borderline and malignant. This classification was supported by a stepwise increase in cytogenetic alterations on CGH. Conclusion Adenomyoepithelial tumours comprise a spectrum of neoplasms consisting of an admixture of glandular and myoepithelial differentiation patterns. As a key component SMA-positive cells co-expressing cytokeratins could be identified. Although categorisation of adenomyoepithelial tumours in benign, borderline and malignant was supported by results of CGH, any assessment of prognosis requires to be firmly based on morphological grounds. At present

  20. Galectin-3 coats the membrane of breast cells and makes a signature of tumours

    KAUST Repository

    Simone, Giuseppina; Malara, Natalia Maria; Trunzo, Valentina; Renne, Maria; Perozziello, Gerardo; Di Fabrizio, Enzo M.; Manz, Andreas

    2014-01-01

    Galectin-3, β-galactoside-binding lectin, coats the membrane of most cancer cells and is involved in metastasis and endothelium recognition as well as in evading immune surveillance through killing of activated T cells. To flag galectin as a biomarker of tumours and metastasis, it is pivotal to understand the role of this protein in different tumours and at different stages. Breast tumours have an anomalous behaviour of the galectin-3 compared to other tumour cells. Herein, FACS sorting and galactoside based assays were used to investigate the role of galectin-3 in metastasis and metastatisation of breast cancer cells. Breast galectin fingerprint at the FACS displayed a higher amount in healthy cells, compared to metastatic cells. The microfluidic assay was able to isolate tumour and metastatic cells more than healthy breast cells. Investigation was performed on samples from patients with breast tumours at stage I and stage III whilst MCF7 and EPH-4 cells were used to perform preliminary investigations. The readout of the conditioned medium (from culturing of stage I cells) fingerprint by FACS evidenced high expression of free galectin. Analysis of the results established that the galectin coating the membrane, by galactoside recognition of the breast cells, and engaged by the cells to form protein-carbohydrate complexes inside the microfluidic assay, resembled the tumour signature of tumours in breast cells whilst the galectin free is independent of those mechanisms. © 2014 The Royal Society of Chemistry.

  1. Risk profile for breast carcinoma and tumour histopathology of medical uninsured patients in Pakistan

    International Nuclear Information System (INIS)

    Raza, U.; Haque, S.U.

    2011-01-01

    Breast carcinoma is an unpredictable disease in the sense that some patients may die at early disease stage due to wide-spread metastasis within six months to one year, while others may survive longer. This study was aimed to evaluate the risk factors for breast carcinoma occurrence and histopathological features of breast carcinoma developed in the social and economical conditions of Pakistan. Methods: A total of 224 female breast cancer diagnosed patients with uncovered medical insurance visiting at the Oncology clinic of a teaching hospital at Karachi, Pakistan were selected for the study. Two hundred and twenty-four (224) healthy female subjects free of any cancer diagnosis were selected as control from different areas of the city. Information on stress, occupation, life history, and life style was obtained through personal interviews. Breast tumour pathology was evaluated for histological grade, lymph node metastasis and hormone receptor status by using standard methods. Student's t-test, Chi-square test and ANOVA were used for comparison. Results: Breast cancer patients in significantly high percentage reported early marriages, abortion occurrence, stressful life style, family cancer history and past disease suffering from diabetes and hypertension. Life style including aerosol chewing and fat rich food intake was significantly high among the patients (p<0.05). On histopathological analysis, patients at the age of 40 years and below were identified in significantly high percentage with tumour grade III, 1-3 lymph node metastasis and hormone receptor negative type. Increasing age was associated with low tumour grade and less percentage of lymph node metastasis. Significantly high percentage of patients were presented with hormone receptor positive tumour (p<0.05). Conclusion: The contributing factors for breast carcinoma occurrence were related to life history and life-style of the patients. Medical insurance uncovered patients at initial diagnosis were

  2. Histopathological review of breast tumours in children and adolescents in Delta State Nigeria

    Directory of Open Access Journals (Sweden)

    Francis Nwachokor

    2013-01-01

    Full Text Available Background: Breast swellings in children and adolescents may be overlooked on assumption that they are physiological enlargement. Pathologic swellings including cancers have however been encountered in this age group. This study highlighted the spectrum of tumours in childhood and adolescents. Materials and Methods: This was a 7 year retrospective analysis of all histologically diagnosed breast tumours in people aged 0 - 19 years. Results: There were 134 breast tumour diagnoses occurring in 133 females and 1 male (gynaecomastia. One hundred and nineteen cases (88.8% were recorded in the 10 - 14 year age group and 15 cases (11.2% in the 15 - 19 year age group. No case was found in children aged less than 10 years. The most common tumour was fibroadenoma accounting for 75.4% (n = 101 of all tumours followed by tubular adenoma (n = 11; 8.2% and adenosis (n = 10; 7.4%. No case of malignancy was recorded in this study. Conclusion: Fibroadenoma is the most common breast tumour in children and adolescents in our environment.

  3. Myofibroblastoma: An Unusual Rapidly Growing Benign Tumour in a Male Breast

    International Nuclear Information System (INIS)

    Rafique, A.; Arshad, A.

    2013-01-01

    Myofibroblastoma is an unusual benign tumour of the breast predominantly seen in men in their sixth to seventh decade. The gross appearance is that of a well circumscribed nodule, characteristically small, seldom exceeding 3 cm. We present a case of an unusually large myofibroblastoma, which mimicked a malignant breast tumour. A 40 years old male, known case of tetralogy of Fallot, was operated in infancy in abroad, presented with a rapid enlargement of right breast over 5 - 6 weeks. Examination revealed a firm 10 cm hemispherical lump occupying the whole of the right breast with normal overlying skin. Since core biopsy was inconclusive, a subcutaneous mastectomy was performed to remove the tumour, which weighed 500 gms. Histopathology and immunocytochemistry revealed a mixed classical and collagenised type of myofibroblastoma. The patient is well with no evidence of recurrence. (author)

  4. The relationship between vascular and metabolic characteristics of primary breast tumours

    International Nuclear Information System (INIS)

    Semple, Scott I.K.; Gilbert, Fiona J.; Redpath, Thomas W.; Staff, Roger T.; Ahearn, Trevor S.; Welch, Andrew E.; Heys, Steven D.; Hutcheon, Andrew W.; Smyth, Elizabeth H.; Chaturvedi, Shailesh

    2004-01-01

    The objective of this study was to investigate the relationship between vascular and metabolic characteristics of breast tumours in vivo, using contrast-enhanced dynamic MRI and 2-[ 18 F] fluoro-2-deoxy-d-glucose (FDG) PET imaging. Twenty patients with large or locally advanced primary breast cancers were imaged prior to therapy. MRI data were acquired using a dynamic gradient echo sequence and analysed using two pharmacokinetic models. Static PET data were acquired in 2D mode. A significant association (P<0.05) was observed between the calculated exchange rate constants of both pharmacokinetic models and calculated PET FDG dose uptake ratios (DUR). Statistical analysis showed that the exchange rate constants can explain between 27 and 44% of the variance observed in the PET FDG uptake ratios. A relationship was demonstrated between the vascular and metabolic characteristics of primary breast tumours showing that any assessment of tumour metabolic activity using PET may be controlled at least in part by delivery of uptake agent due to the vascular characteristics of the tumour. MRI and PET provide methods of assessing breast tumour vascularity and metabolism in vivo using the exchange rate constants of dynamic MRI, and DUR of PET, respectively, these measures being related but not equivalent. (orig.)

  5. The relationship between tumour size, nodal status and distant metastases: on the origins of breast cancer.

    Science.gov (United States)

    Sopik, Victoria; Narod, Steven A

    2018-04-24

    In patients with breast cancer, increasing tumour size at diagnosis is associated with an increased likelihood of axillary lymph node involvement and increased breast cancer-specific mortality. However, this relation is based on studies which combine all tumours smaller than 1.0 cm in a single category and all tumours larger than 5.0 cm in another category. This coarse classification may obscure a nuanced description of the effects of tumour size across the full range of possible sizes. We examined the relationship between primary tumour size, lymph node status and distant metastases in a cohort of 819,647 women diagnosed with first primary invasive breast cancer from 1990 to 2014 in the Surveillance, Epidemiology and End Results (SEER) registries database. All patients in the cohort had a known primary tumour size between 1 and 150 mm in greatest dimension. Primary tumour size was examined as a continuous (1-150 mm) and categorical variable (15 size groups; 10-mm intervals). For each 1- or 10-mm size group, we determined the proportion of patients with positive lymph nodes at diagnosis, the proportion of patients with distant metastases at diagnosis and the actuarial cumulative risk of breast cancer-specific mortality at 15 years from diagnosis. Among 819,647 patients with invasive breast tumours between 1 and 150 mm in size, there was a non-linear correlation between increasing tumour size and the prevalence of lymph node metastases at diagnosis (% node-positive), the prevalence of distant metastases at diagnosis (% stage IV) and the 15-year rate of breast cancer-specific mortality across the entire size spectrum. For very small tumours (under 10 mm) and for very large tumours (larger than 60-90 mm) there was little correlation between tumour size and metastasis risk. The relationship between tumour size, lymph node status and distant metastases in patients with invasive breast cancer is not linear. This calls into question the conventional model that the

  6. Modelling breast cancer tumour growth for a stable disease population.

    Science.gov (United States)

    Isheden, Gabriel; Humphreys, Keith

    2017-01-01

    Statistical models of breast cancer tumour progression have been used to further our knowledge of the natural history of breast cancer, to evaluate mammography screening in terms of mortality, to estimate overdiagnosis, and to estimate the impact of lead-time bias when comparing survival times between screen detected cancers and cancers found outside of screening programs. Multi-state Markov models have been widely used, but several research groups have proposed other modelling frameworks based on specifying an underlying biological continuous tumour growth process. These continuous models offer some advantages over multi-state models and have been used, for example, to quantify screening sensitivity in terms of mammographic density, and to quantify the effect of body size covariates on tumour growth and time to symptomatic detection. As of yet, however, the continuous tumour growth models are not sufficiently developed and require extensive computing to obtain parameter estimates. In this article, we provide a detailed description of the underlying assumptions of the continuous tumour growth model, derive new theoretical results for the model, and show how these results may help the development of this modelling framework. In illustrating the approach, we develop a model for mammography screening sensitivity, using a sample of 1901 post-menopausal women diagnosed with invasive breast cancer.

  7. Histopathological features of breast tumours in BRCA1, BRCA2 and mutation-negative breast cancer families

    International Nuclear Information System (INIS)

    Eerola, Hannaleena; Heikkilä, Päivi; Tamminen, Anitta; Aittomäki, Kristiina; Blomqvist, Carl; Nevanlinna, Heli

    2005-01-01

    Histopathological features of BRCA1 and BRCA2 tumours have previously been characterised and compared with unselected breast tumours; however, familial non-BRCA1/2 tumours are less well known. The aim of this study was to characterise familial non-BRCA1/2 tumours and to evaluate routine immunohistochemical and pathological markers that could help us to further distinguish families carrying BRCA1/2 mutations from other breast cancer families. Breast cancer tissue specimens (n = 262) from 25 BRCA1, 20 BRCA2 and 74 non-BRCA1/2 families were studied on a tumour tissue microarray. Immunohistochemical staining of oestrogen receptor (ER), progesterone receptor (PgR) and p53 as well as the histology and grade of these three groups were compared with each other and with the respective information on 862 unselected control patients from the archives of the Pathology Department of Helsinki University Central Hospital. Immunohistochemical staining of erbB2 was also performed among familial cases. BRCA1-associated cancers were diagnosed younger and were more ER-negative and PgR-negative, p53-positive and of higher grade than the other tumours. However, in multivariate analysis the independent factors compared with non-BRCA1/2 tumours were age, grade and PgR negativity. BRCA2 cases did not have such distinctive features compared with non-BRCA1/2 tumours or with unselected control tumours. Familial cases without BRCA1/2 mutations had tumours of lower grade than the other groups. BRCA1 families differed from mutation-negative families by age, grade and PgR status, whereas ER status was not an independent marker

  8. Risk for new tumours after treatment of breast cancer of women

    International Nuclear Information System (INIS)

    Boice, J.D.

    1988-01-01

    In this article the chance for a new tumour after a succesful treatment of breast cancer is worked out. The chance of a second tumour for treated women turns out to be three times as large as the change which an arbitrary group of contemporaries has of cancer. These (second) tumours mostly occur in the other breast. It is not quite clear in how far treatment with ionizing radiation can influence the origin of new tumours. The chance for re-occurring of breast cancer appears to be somewhat higher for women who underwent radiotherapy than for woman who were treated otherwise. Also leukemia occurred more often in women treated with than without ionnizing radiation; however, absolutely seen it does concern very small numbers. The importance of a good registration of cancer and the way of treatment of cancer are illustrated. Epidemiologic research as described may contribute in finding the most effective treatment with the least side effects. (H.W.). 15 refs.; 3 figs.; 3 tabs

  9. Staging primary breast cancer. Are there tumour pathological features that correlate with a false-negative axillary ultrasound?

    International Nuclear Information System (INIS)

    Johnson, S.; Brown, S.; Porter, G.; Steel, J.; Paisley, K.; Watkins, R.; Holgate, C.

    2011-01-01

    Aim: To investigate whether the histopathological characteristics of primary breast cancer tumours could predict the likelihood of false-negative axillary ultrasound. Materials and methods: Screening and symptomatic patients were identified from pathology records and imaging and pathology records reviewed. True and false-negative axillary staging ultrasound groups were compared statistically in terms of tumour size, pathological type and grade, lymphovascular invasion, and oestrogen receptor (ER) status. Results: Of 155 women with normal ultrasounds, 45 (29%) were node positive at axillary surgery. Breast tumour size was significantly different with the average size smaller in the true-negative group: 21 versus 30 mm (p < 0.02). The histological type varied significantly between the groups, with more lobular carcinomas in the false-negative group [6/110 (5%) versus 6/45 (13%), p < 0.001]. The false-negative group was also more likely to show lymphovascular invasion in the breast [6/110 (5%) versus 14/45 (31%), p < 0.001]. There was no significant difference in tumour grade or ER status. Conclusion: The present study has found significant differences in tumour characteristics between women with true-negative and false-negative axillary staging ultrasound in terms of size, primary tumour histological type and presence of lymphovascular invasion. In particular, axillary ultrasound in primary lobular carcinoma may be less accurate and a negative result is more likely to be spurious than with primary ductal carcinomas.

  10. Contrast kinetics of the malignant breast tumour - border versus centre enhancement on dynamic midfield MRI

    DEFF Research Database (Denmark)

    Marklund, M.; Torp-Pedersen, S.; Bentzon, N.

    2008-01-01

    receptor negative tumours. CONCLUSION: The border/centre enhancement difference in malignant breast tumours is easily visualized on midfield dynamic magnetic resonance mammography. The dynamic behaviour is significantly correlated to histological features and receptor status of the tumours Udgivelsesdato......PURPOSE: To quantify the border versus centre enhancement of malignant breast tumours on dynamic magnetic resonance mammography. MATERIALS AND METHODS: Fifty-two women diagnosed with primary breast cancer underwent dynamic magnetic resonance mammography (Omniscan 0.2 mmol/kg bodyweight......) on a midfield scanner (0.6 T), prior to surgery. The following five variables were recorded from the border and centre regions of the tumours: Early Enhancement, Time to Peak, Wash-in rate, Wash-out rate and Area under Curve. Information on histology type, oestrogen and progesterone receptor status...

  11. AN UNUSUAL PRESENTATION OF A HUGE BREAST TUMOUR IN AN ELDERLY FEMALE: A CASE REPORT

    OpenAIRE

    Prasenjit; Sudipta; Subir Kumar; Himadri Sekhar; Amalesh

    2014-01-01

    Pleomorphic breast carcinoma is a rare variety of breast carcinoma, with a highly aggresive behaviour and poor prognosis, which usually presents after 50 years of age. Our case presented in a very similar way as phyllodes’ tumour of breast (even the FNAC report also suggested it as a case of phyllodes’ tumour). But postoperative histopathological report clearly revealed it as a case of this rare entity of pleomorphic carcinoma of breast

  12. Background parenchymal enhancement on breast MRI and mammographic breast density: correlation with tumour characteristics

    International Nuclear Information System (INIS)

    Kim, M.Y.; Choi, N.; Yang, J.-H.; Yoo, Y.B.; Park, K.S.

    2015-01-01

    Aim: To investigate the relationship between mammographic breast density (MGD) and background parenchymal enhancement (BPE) at breast MRI and histopathological features of invasive breast cancers. Materials and methods: A total of 178 women with unilateral invasive breast cancer who preoperatively underwent mammography and breast MRI were included in the study. Two radiologists rated MGD and BPE according to BI-RADS criteria in consensus. The relationship between MGD and BPE was investigated, and compared with histopathological features of invasive breast cancers according to the level of MGD and BPE. Results: At MRI, there is no significant difference in the distribution of MGD and BPE of the contralateral breast in women with invasive breast cancer according to menopausal status (p=0.226, 0.384). Women with high MGD (>50% glandular) were more likely to have oestrogen-receptor (ER)-positive breast cancer (p=0.045) and progesterone receptor (PR)-positive breast cancer (p=0.020). With regard to BPE, PR positivity correlated with moderate or marked BPE with borderline significance (p=0.054). Multivariate logistic regression analyses revealed that women with high MGD were less likely to have triple-negative (i.e., a cancer that is ER negative, PR negative, and human epidermal growth factor receptor type 2 [HER2] negative) breast cancer compared with ER (+)/HER2 (−) cancer (OR=0.231, 95% CI: 0.070, 0.760; p=0.016). No association between the histological tumour characteristics and BPE was observed. Conclusion: In women with invasive breast cancer, high MGD is associated with ER positivity of the invasive breast cancer. However, at MRI, BPE of the contralateral breast seems to be independent of tumour characteristics. -- Highlights: •There is no difference in distribution of MGD and BPE of contralateral breast on MRI. •High MGD is associated with ER positivity of the invasive breast cancer. •BPE of the contralateral breast on MRI is independent of tumor

  13. Inflamed Phylloides Tumour in a Girl: A Challenging Diagnosis in Paediatric Breast Lesions

    Directory of Open Access Journals (Sweden)

    Ilaria Testa

    2018-05-01

    Full Text Available Introduction: Phylloides tumours (PTs are rare fibroepithelial neoplasms that account for 0.3–0.9% of all breast tumours. These tumours typically occur in women aged 30–70 years. The occurrence of these tumours in older children and adolescents poses particular diagnostic and therapeutic problems. However, early diagnosis is mandatory because although most of the cases of PTs in children are benign, the borderline and malignant cases with potential negative outcomes cannot be excluded. Case presentation: A 12-year-old girl presented at the Paediatric Emergency Department for hyperaemia and warmth of the left breast that occurred a few days prior without fever. The girl experienced menarche 8 months previously. She experienced no previous trauma and she had no family history of breast cancer. On physical examination, the left breast was painful, enlarged and tender. The overlying skin was erythematous and warm. A breast ultrasonography (US revealed a large mass with features of an abscess, including a hyperechoic wall, scattered internal echoes and hypoechoic peripheral lacunae of apparent colliquative nature. After 4 days of unsuccessful antibiotic therapy, surgical drainage was performed due to the suspicion of a mammary abscess. At the surgical incision site, the lesion was not-well circumscribed and lacked a capsule. In addition, purulent material was not detected. Histological examination revealed that the tissue alterations were compatible with benign PT. With this diagnosis, the girl underwent definitive surgical removal of the lesion. The postoperative period passed without negative events. An US performed 6 months later revealed that no new mass was present at this time, suggesting no recurrence of the tumour. Conclusion: This case shows that in the presence of a clinical picture suggesting the inflammation of the breast in adolescent females, PT should be considered as a possible diagnosis and US-guided core biopsy should be

  14. Inflamed Phylloides Tumour in a Girl: A Challenging Diagnosis in Paediatric Breast Lesions.

    Science.gov (United States)

    Testa, Ilaria; Salvatori, Cristina; Prestipino, Marco; Laurenti, Maria Elena; Gerli, Paolo; Di Cara, Giuseppe; Principi, Nicola; Esposito, Susanna; Bertozzi, Mirko

    2018-05-11

    Introduction : Phylloides tumours (PTs) are rare fibroepithelial neoplasms that account for 0.3⁻0.9% of all breast tumours. These tumours typically occur in women aged 30⁻70 years. The occurrence of these tumours in older children and adolescents poses particular diagnostic and therapeutic problems. However, early diagnosis is mandatory because although most of the cases of PTs in children are benign, the borderline and malignant cases with potential negative outcomes cannot be excluded. Case presentation : A 12-year-old girl presented at the Paediatric Emergency Department for hyperaemia and warmth of the left breast that occurred a few days prior without fever. The girl experienced menarche 8 months previously. She experienced no previous trauma and she had no family history of breast cancer. On physical examination, the left breast was painful, enlarged and tender. The overlying skin was erythematous and warm. A breast ultrasonography (US) revealed a large mass with features of an abscess, including a hyperechoic wall, scattered internal echoes and hypoechoic peripheral lacunae of apparent colliquative nature. After 4 days of unsuccessful antibiotic therapy, surgical drainage was performed due to the suspicion of a mammary abscess. At the surgical incision site, the lesion was not-well circumscribed and lacked a capsule. In addition, purulent material was not detected. Histological examination revealed that the tissue alterations were compatible with benign PT. With this diagnosis, the girl underwent definitive surgical removal of the lesion. The postoperative period passed without negative events. An US performed 6 months later revealed that no new mass was present at this time, suggesting no recurrence of the tumour. Conclusion : This case shows that in the presence of a clinical picture suggesting the inflammation of the breast in adolescent females, PT should be considered as a possible diagnosis and US-guided core biopsy should be considered to confirm

  15. Primary breast cancer tumours contain high amounts of IgA1 immunoglobulin

    DEFF Research Database (Denmark)

    Welinder, Charlotte; Baldetorp, Bo; Blixt, Klas Ola

    2013-01-01

    seen in the percentage of stained cells and in the staining pattern in the different breast cancers analysed. Anti-Tn antibody and HPA were also shown to specifically bind to a number of possible constellations of the Tn antigen in the hinge region of IgA1. Both reagents could also detect the presence....... The short O-glycan that forms the antigen is carried by a number of different proteins. One potential carrier of the Tn antigen is immunoglobulin A1 (IgA1), which we surprisingly found in tumour cells of the invasive parts of primary breast carcinoma. Conventional immunohistochemical analysis of paraffin......-embedded sections from primary breast cancers showed IgA1 to be present in the cytoplasm and plasma membrane of 35 out of 36 individual primary tumours. The immunohistochemical staining of HPA and anti-Tn antibody (GOD3-2C4) did to some extent overlap with the presence of IgA1 in the tumours, but differences were...

  16. [Giant juvenile fibroadenoma - a benign and rare tumour of the breast in adolescent girls].

    Science.gov (United States)

    Hasanbegovic, Emir; Talman, Maj-Lis Møller; Hjalgrim, Lisa Lyngsie; Lausen, Iver Michael Gudme

    2014-03-03

    A rapidly growing mass in the breast may be stressful for both parents and child as the suspicion of malignancy arises. The purpose of this case report is to draw attention to the fact that most emerging lesions of the breast in girls during puberty are benign. This case report presents a ten-year-old girl with a rapidly growing tumour in the breast. The tumour turned out to be a giant juvenile fibroadenoma, which is rare and benign. Differential diagnosis, investigation and management are reviewed.

  17. Increased risk of breast cancer development after diagnosis of salivary gland tumour

    NARCIS (Netherlands)

    In der Maur, Caroline D.; Klokman, Willem J.; van Leeuwen, Floor E.; Tan, I. Bing; Rutgers, Emiel J. Th; Balm, Alfons J. M.

    2005-01-01

    The aim of this study was to evaluate whether patients with salivary gland tumours are at increased risk of developing breast cancer. A retrospective cohort study was performed. Female patients (n = 439) with a salivary gland tumour (major and minor) were included. The diagnosis was confirmed

  18. Biochemical study on some tumour angiogenesis factors and inhibitors in breast cancer

    International Nuclear Information System (INIS)

    Mohamed, N.M.E

    2007-01-01

    This pilot study was undertaken to investigate the significance of some tumour angiogenic factors (e.g. MMP, ADAM-12 and VEGF) and tumour angiogenic inhibitors (endostatin and TIMP-1) in the aetiology of breast cancer and their responsiveness to cancer treatment as well . We also sought to assess the significance of these angiogenic and antiangiogenic factors in the prognosis and diagnosis of breast cancer. The cases were allocated into five groups: Normal control group (Gr.l), fibroadenoma (Gr.l l), breast cancer (invasive duct carcinoma type grade l l) (Gr.lll) , breast cancer + chemo hormonal therapy (Gr.IV), and breast cancer + chemo hormonal and radiotherapy (Gr.V).Results obtained from this study reported absence of matrix metalloproteinase-9 (MMP-9)activity in the urine and serum of normal subjects and fibroadenoma patients and its significant depression in the urine and serum of breast cancer patients treated with chemo hormonal therapy alone or followed by radiotherapy, compared to breast cancer group as reference. A significantly mild elevation in urinary MMP-2 activity and a non significant change in its activity in the serum of fibroadenoma patients, compared to the dramatic rise in the urine and serum of breast cancer patients were observed

  19. Pathobiological features of breast tumours in the State of Kuwait: a comprehensive analysis

    Directory of Open Access Journals (Sweden)

    Abdeen Suad

    2007-01-01

    Full Text Available Abstract Background Breast cancer accounts for 30.3% of all cancer types in Kuwaiti women. Death occurs in approximately 43% of these patients. Our goal was to conduct a comprehensive analysis of the pathobiological characteristics of the tumours in an attempt to determine any particular trend that could be present. Methods One hundred and sixty-six cases were included in this study. All the pathology reports and paraffin blocks pertaining to these cases were collected. Four micrometer sections were taken from each block, and immunostaining against Her-2, ER, and PgR was performed. Both the proportion and intensity of immunostaining were scored according to the Allred's method, and typing of the tumour was done according the WHO criteria regarding tumour classification. Grading of invasive carcinomas was done according to the modified Bloom-Richardson-Elston's method, and tumour stage was determined according to the criteria set by the American Joint Committee on Cancer. Results The mean age of the patients below 55 years was 40, as compared to 68 for those above 55 (p < 0.0001. More than half of the cases were in the right breast, and were surgically treated by total mastectomy with axillary clearance. The majority of the tumours had irregular (stellate margins, was invasive, and had a surrounding breast tissue of adenosis or fibrocystic type. Their mitotic index was 10–20 or >20 with a marked to moderate nuclear pleomorphism. They were mostly grade II or III, sized 2–5 or > 5 cm, had absent or scanty tumour lymphocytes, and were stage II or III. The in situ tumours were mainly ductal carcinoma (DCIS of which comedo and cribriform were the major histological subtypes. The major histological subtypes of the invasive tumours were ductal-not otherwise specified, lobular, and tubular/cribriform. In this study, we also found a significant (p < 0.05 association between over expression of Her-2, lack of expression of ER and some of the

  20. Analysis of the progression of fibroepithelial tumours of the breast by PCR-based clonality assay

    NARCIS (Netherlands)

    Kuijper, Arno; Buerger, H.; Simon, R.; Schaefer, K-L.; Croonen, A.; Boecker, W.; Wall, E. van der; Diest, P.J. van

    2002-01-01

    Fibroadenoma and phyllodes tumour of the breast are both fibroepithelial tumours. Although progression to epithelial malignancy has been described, the behaviour of most fibroadenomas is benign. Phyllodes tumours, on the other hand, can display locally destructive growth and can even metastasize. A

  1. No evidence for promoter region methylation of the succinate dehydrogenase and fumarate hydratase tumour suppressor genes in breast cancer

    Directory of Open Access Journals (Sweden)

    Dobrovic Alexander

    2009-09-01

    Full Text Available Abstract Background Succinate dehydrogenase (SDH and fumarate hydratase (FH are tricarboxylic acid (TCA cycle enzymes that are also known to act as tumour suppressor genes. Increased succinate or fumarate levels as a consequence of SDH and FH deficiency inhibit hypoxia inducible factor-1α (HIF-1α prolyl hydroxylases leading to sustained HIF-1α expression in tumours. Since HIF-1α is frequently expressed in breast carcinomas, DNA methylation at the promoter regions of the SDHA, SDHB, SDHC and SDHD and FH genes was evaluated as a possible mechanism in silencing of SDH and FH expression in breast carcinomas. Findings No DNA methylation was identified in the promoter regions of the SDHA, SDHB, SDHC, SDHD and FH genes in 72 breast carcinomas and 10 breast cancer cell lines using methylation-sensitive high resolution melting which detects both homogeneous and heterogeneous methylation. Conclusion These results show that inactivation via DNA methylation of the promoter CpG islands of SDH and FH is unlikely to play a major role in sporadic breast carcinomas.

  2. Intra-Tumour Signalling Entropy Determines Clinical Outcome in Breast and Lung Cancer

    Science.gov (United States)

    Banerji, Christopher R. S.; Severini, Simone; Caldas, Carlos; Teschendorff, Andrew E.

    2015-01-01

    The cancer stem cell hypothesis, that a small population of tumour cells are responsible for tumorigenesis and cancer progression, is becoming widely accepted and recent evidence has suggested a prognostic and predictive role for such cells. Intra-tumour heterogeneity, the diversity of the cancer cell population within the tumour of an individual patient, is related to cancer stem cells and is also considered a potential prognostic indicator in oncology. The measurement of cancer stem cell abundance and intra-tumour heterogeneity in a clinically relevant manner however, currently presents a challenge. Here we propose signalling entropy, a measure of signalling pathway promiscuity derived from a sample’s genome-wide gene expression profile, as an estimate of the stemness of a tumour sample. By considering over 500 mixtures of diverse cellular expression profiles, we reveal that signalling entropy also associates with intra-tumour heterogeneity. By analysing 3668 breast cancer and 1692 lung adenocarcinoma samples, we further demonstrate that signalling entropy correlates negatively with survival, outperforming leading clinical gene expression based prognostic tools. Signalling entropy is found to be a general prognostic measure, valid in different breast cancer clinical subgroups, as well as within stage I lung adenocarcinoma. We find that its prognostic power is driven by genes involved in cancer stem cells and treatment resistance. In summary, by approximating both stemness and intra-tumour heterogeneity, signalling entropy provides a powerful prognostic measure across different epithelial cancers. PMID:25793737

  3. Intra-tumour signalling entropy determines clinical outcome in breast and lung cancer.

    Directory of Open Access Journals (Sweden)

    Christopher R S Banerji

    2015-03-01

    Full Text Available The cancer stem cell hypothesis, that a small population of tumour cells are responsible for tumorigenesis and cancer progression, is becoming widely accepted and recent evidence has suggested a prognostic and predictive role for such cells. Intra-tumour heterogeneity, the diversity of the cancer cell population within the tumour of an individual patient, is related to cancer stem cells and is also considered a potential prognostic indicator in oncology. The measurement of cancer stem cell abundance and intra-tumour heterogeneity in a clinically relevant manner however, currently presents a challenge. Here we propose signalling entropy, a measure of signalling pathway promiscuity derived from a sample's genome-wide gene expression profile, as an estimate of the stemness of a tumour sample. By considering over 500 mixtures of diverse cellular expression profiles, we reveal that signalling entropy also associates with intra-tumour heterogeneity. By analysing 3668 breast cancer and 1692 lung adenocarcinoma samples, we further demonstrate that signalling entropy correlates negatively with survival, outperforming leading clinical gene expression based prognostic tools. Signalling entropy is found to be a general prognostic measure, valid in different breast cancer clinical subgroups, as well as within stage I lung adenocarcinoma. We find that its prognostic power is driven by genes involved in cancer stem cells and treatment resistance. In summary, by approximating both stemness and intra-tumour heterogeneity, signalling entropy provides a powerful prognostic measure across different epithelial cancers.

  4. An imbalance in progenitor cell populations reflects tumour progression in breast cancer primary culture models

    LENUS (Irish Health Repository)

    Donatello, Simona

    2011-04-26

    Abstract Background Many factors influence breast cancer progression, including the ability of progenitor cells to sustain or increase net tumour cell numbers. Our aim was to define whether alterations in putative progenitor populations could predict clinicopathological factors of prognostic importance for cancer progression. Methods Primary cultures were established from human breast tumour and adjacent non-tumour tissue. Putative progenitor cell populations were isolated based on co-expression or concomitant absence of the epithelial and myoepithelial markers EPCAM and CALLA respectively. Results Significant reductions in cellular senescence were observed in tumour versus non-tumour cultures, accompanied by a stepwise increase in proliferation:senescence ratios. A novel correlation between tumour aggressiveness and an imbalance of putative progenitor subpopulations was also observed. Specifically, an increased double-negative (DN) to double-positive (DP) ratio distinguished aggressive tumours of high grade, estrogen receptor-negativity or HER2-positivity. The DN:DP ratio was also higher in malignant MDA-MB-231 cells relative to non-tumourogenic MCF-10A cells. Ultrastructural analysis of the DN subpopulation in an invasive tumour culture revealed enrichment in lipofuscin bodies, markers of ageing or senescent cells. Conclusions Our results suggest that an imbalance in tumour progenitor subpopulations imbalances the functional relationship between proliferation and senescence, creating a microenvironment favouring tumour progression.

  5. Activity of mevalonate pathway inhibitors against breast and ovarian cancers in the ATP-based tumour chemosensitivity assay

    International Nuclear Information System (INIS)

    Knight, Louise A; Kurbacher, Christian M; Glaysher, Sharon; Fernando, Augusta; Reichelt, Ralf; Dexel, Susanne; Reinhold, Uwe; Cree, Ian A

    2009-01-01

    Previous data suggest that lipophilic statins such as fluvastatin and N-bisphosphonates such as zoledronic acid, both inhibitors of the mevalonate metabolic pathway, have anti-cancer effects in vitro and in patients. We have examined the effect of fluvastatin alone and in combination with zoledronic acid in the ATP-based tumour chemosensitivity assay (ATP-TCA) for effects on breast and ovarian cancer tumour-derived cells. Both zoledronic acid and fluvastatin showed activity in the ATP-TCA against breast and ovarian cancer, though fluvastatin alone was less active, particularly against breast cancer. The combination of zoledronic acid and fluvastatin was more active than either single agent in the ATP-TCA with some synergy against breast and ovarian cancer tumour-derived cells. Sequential drug experiments showed that pre-treatment of ovarian tumour cells with fluvastatin resulted in decreased sensitivity to zoledronic acid. Addition of mevalonate pathway components with zoledronic acid with or without fluvastatin showed little effect, while mevalonate did reduced inhibition due to fluvastatin. These data suggest that the combination of zoledronic acid and fluvastatin may have activity against breast and ovarian cancer based on direct anti-cancer cell effects. A clinical trial to test this is in preparation

  6. Background parenchymal enhancement in breast MRI before and after neoadjuvant chemotherapy: correlation with tumour response

    Energy Technology Data Exchange (ETDEWEB)

    Preibsch, H.; Wanner, L.; Bahrs, S.D.; Wietek, B.M.; Nikolaou, K.; Wiesinger, B. [University Hospital Tuebingen, Diagnostic and Interventional Radiology, Tuebingen (Germany); Siegmann-Luz, K.C. [Diagnostic Center for Breast Cancer and Screening Mammography Brandenburg Ost, Koenigs Wusterhausen (Germany); Oberlecher, E.; Hahn, M. [University Hospital Tuebingen, Department of Gynecology and Obstetrics, Tuebingen (Germany); Staebler, A. [University Hospital Tuebingen, Institute of Pathology and Neuropathology, Tuebingen (Germany)

    2016-06-15

    To correlate the decrease in background parenchymal enhancement (BPE) and tumour response measured with MRI in breast cancer patients treated with neoadjuvant chemotherapy (NAC). One hundred and forty-six MRI examinations of 73 patients with 80 biopsy-proven breast cancers who underwent breast MRI before and after NAC were retrospectively analysed. All images were reviewed by two blinded readers, who classified BPE into categories (BEC; 1 = minimal, 2 = mild, 3 = moderate, 4 = marked) before and after NAC. Histopathological and morphological tumour responses were analysed and compared. The distribution of BEC 1/2/3/4 was 25/46/18/11 % before and 78/20/2/0 % after NAC. On average, BPE decreased by 0.87 BEC. Cohen's kappa showed substantial agreement (k = 0.73-0.77) before and moderate agreement (k = 0.43-0.60) after NAC and moderate agreement (k = 0.62-0.60) concerning the change in BEC. Correlating the change in BPE with tumour response, the average decrease in BEC was 1.3 in cases of complete remission, 0.83 in cases with partial response, 0.85 in cases with stable disease and 0.40 in cases with progressive disease. Correlation analysis showed a significant correlation between the decrease in BEC and tumour response (r = -0.24, p = 0.03). BPE decreased by, on average, 0.87 BEC following NAC for breast cancer. The degree of BPE reduction seemed to correlate with tumour response. (orig.)

  7. Gene expression of circulating tumour cells in breast cancer patients

    Directory of Open Access Journals (Sweden)

    Bölke E

    2009-09-01

    Full Text Available Abstract Background The diagnostic tools to predict the prognosis in patients suffering from breast cancer (BC need further improvements. New technological achievements like the gene profiling of circulating tumour cells (CTC could help identify new prognostic markers in the clinical setting. Furthermore, gene expression patterns of CTC might provide important informations on the mechanisms of tumour cell metastasation. Materials and methods We performed realtime-PCR and multiplex-PCR analyses following immunomagnetic separation of CTC. Peripheral blood (PB samples of 63 patients with breast cancer of various stages were analyzed and compared to a control group of 14 healthy individuals. After reverse-transcription, we performed multiplex PCR using primers for the genes ga733.3, muc-1 and c-erbB2. Mammaglobin1, spdef and c-erbB2 were analyzed applying realtime-PCR. Results ga733.2 overexpression was found in 12.7% of breast cancer cases, muc-1 in 15.9%, mgb1 in 9.1% and spdef in 12.1%. In this study, c-erbB2 did not show any significant correlation to BC, possibly due to a highly ambient expression. Besides single gene analyses, gene profiles were additionally evaluated. Highly significant correlations to BC were found in single gene analyses of ga733.2 and muc-1 and in gene profile analyses of ga733.3*muc-1 and GA7 ga733.3*muc-1*mgb1*spdef. Conclusion Our study reveals that the single genes ga733.3, muc-1 and the gene profiles ga733.3*muc-1 and ga733.3*3muc-1*mgb1*spdef can serve as markers for the detection of CTC in BC. The multigene analyses found highly positive levels in BC patients. Our study indicates that not single gene analyses but subtle patterns of multiple genes lead to rising accuracy and low loss of specificity in detection of breast cancer cases.

  8. Epstein-Barr virus, human papillomavirus and mouse mammary tumour virus as multiple viruses in breast cancer.

    Science.gov (United States)

    Glenn, Wendy K; Heng, Benjamin; Delprado, Warick; Iacopetta, Barry; Whitaker, Noel J; Lawson, James S

    2012-01-01

    The purpose of this investigation is to determine if Epstein Barr virus (EBV), high risk human papillomavirus (HPV), and mouse mammary tumour viruses (MMTV) co-exist in some breast cancers. All the specimens were from women residing in Australia. For investigations based on standard PCR, we used fresh frozen DNA extracts from 50 unselected invasive breast cancers. For normal breast specimens, we used DNA extracts from epithelial cells from milk donated by 40 lactating women. For investigations based on in situ PCR we used 27 unselected archival formalin fixed breast cancer specimens and 18 unselected archival formalin fixed normal breast specimens from women who had breast reduction surgery. Thirteen of these fixed breast cancer specimens were ductal carcinoma in situ (dcis) and 14 were predominantly invasive ductal carcinomas (idc). EBV sequences were identified in 68%, high risk HPV sequences in 50%, and MMTV sequences in 78% of DNA extracted from 50 invasive breast cancer specimens. These same viruses were identified in selected normal and breast cancer specimens by in situ PCR. Sequences from more than one viral type were identified in 72% of the same breast cancer specimens. Normal controls showed these viruses were also present in epithelial cells in human milk - EBV (35%), HPV, 20%) and MMTV (32%) of 40 milk samples from normal lactating women, with multiple viruses being identified in 13% of the same milk samples. We conclude that (i) EBV, HPV and MMTV gene sequences are present and co-exist in many human breast cancers, (ii) the presence of these viruses in breast cancer is associated with young age of diagnosis and possibly an increased grade of breast cancer.

  9. Association analysis identifies 65 new breast cancer risk loci.

    Science.gov (United States)

    Michailidou, Kyriaki; Lindström, Sara; Dennis, Joe; Beesley, Jonathan; Hui, Shirley; Kar, Siddhartha; Lemaçon, Audrey; Soucy, Penny; Glubb, Dylan; Rostamianfar, Asha; Bolla, Manjeet K; Wang, Qin; Tyrer, Jonathan; Dicks, Ed; Lee, Andrew; Wang, Zhaoming; Allen, Jamie; Keeman, Renske; Eilber, Ursula; French, Juliet D; Qing Chen, Xiao; Fachal, Laura; McCue, Karen; McCart Reed, Amy E; Ghoussaini, Maya; Carroll, Jason S; Jiang, Xia; Finucane, Hilary; Adams, Marcia; Adank, Muriel A; Ahsan, Habibul; Aittomäki, Kristiina; Anton-Culver, Hoda; Antonenkova, Natalia N; Arndt, Volker; Aronson, Kristan J; Arun, Banu; Auer, Paul L; Bacot, François; Barrdahl, Myrto; Baynes, Caroline; Beckmann, Matthias W; Behrens, Sabine; Benitez, Javier; Bermisheva, Marina; Bernstein, Leslie; Blomqvist, Carl; Bogdanova, Natalia V; Bojesen, Stig E; Bonanni, Bernardo; Børresen-Dale, Anne-Lise; Brand, Judith S; Brauch, Hiltrud; Brennan, Paul; Brenner, Hermann; Brinton, Louise; Broberg, Per; Brock, Ian W; Broeks, Annegien; Brooks-Wilson, Angela; Brucker, Sara Y; Brüning, Thomas; Burwinkel, Barbara; Butterbach, Katja; Cai, Qiuyin; Cai, Hui; Caldés, Trinidad; Canzian, Federico; Carracedo, Angel; Carter, Brian D; Castelao, Jose E; Chan, Tsun L; David Cheng, Ting-Yuan; Seng Chia, Kee; Choi, Ji-Yeob; Christiansen, Hans; Clarke, Christine L; Collée, Margriet; Conroy, Don M; Cordina-Duverger, Emilie; Cornelissen, Sten; Cox, David G; Cox, Angela; Cross, Simon S; Cunningham, Julie M; Czene, Kamila; Daly, Mary B; Devilee, Peter; Doheny, Kimberly F; Dörk, Thilo; Dos-Santos-Silva, Isabel; Dumont, Martine; Durcan, Lorraine; Dwek, Miriam; Eccles, Diana M; Ekici, Arif B; Eliassen, A Heather; Ellberg, Carolina; Elvira, Mingajeva; Engel, Christoph; Eriksson, Mikael; Fasching, Peter A; Figueroa, Jonine; Flesch-Janys, Dieter; Fletcher, Olivia; Flyger, Henrik; Fritschi, Lin; Gaborieau, Valerie; Gabrielson, Marike; Gago-Dominguez, Manuela; Gao, Yu-Tang; Gapstur, Susan M; García-Sáenz, José A; Gaudet, Mia M; Georgoulias, Vassilios; Giles, Graham G; Glendon, Gord; Goldberg, Mark S; Goldgar, David E; González-Neira, Anna; Grenaker Alnæs, Grethe I; Grip, Mervi; Gronwald, Jacek; Grundy, Anne; Guénel, Pascal; Haeberle, Lothar; Hahnen, Eric; Haiman, Christopher A; Håkansson, Niclas; Hamann, Ute; Hamel, Nathalie; Hankinson, Susan; Harrington, Patricia; Hart, Steven N; Hartikainen, Jaana M; Hartman, Mikael; Hein, Alexander; Heyworth, Jane; Hicks, Belynda; Hillemanns, Peter; Ho, Dona N; Hollestelle, Antoinette; Hooning, Maartje J; Hoover, Robert N; Hopper, John L; Hou, Ming-Feng; Hsiung, Chia-Ni; Huang, Guanmengqian; Humphreys, Keith; Ishiguro, Junko; Ito, Hidemi; Iwasaki, Motoki; Iwata, Hiroji; Jakubowska, Anna; Janni, Wolfgang; John, Esther M; Johnson, Nichola; Jones, Kristine; Jones, Michael; Jukkola-Vuorinen, Arja; Kaaks, Rudolf; Kabisch, Maria; Kaczmarek, Katarzyna; Kang, Daehee; Kasuga, Yoshio; Kerin, Michael J; Khan, Sofia; Khusnutdinova, Elza; Kiiski, Johanna I; Kim, Sung-Won; Knight, Julia A; Kosma, Veli-Matti; Kristensen, Vessela N; Krüger, Ute; Kwong, Ava; Lambrechts, Diether; Le Marchand, Loic; Lee, Eunjung; Lee, Min Hyuk; Lee, Jong Won; Neng Lee, Chuen; Lejbkowicz, Flavio; Li, Jingmei; Lilyquist, Jenna; Lindblom, Annika; Lissowska, Jolanta; Lo, Wing-Yee; Loibl, Sibylle; Long, Jirong; Lophatananon, Artitaya; Lubinski, Jan; Luccarini, Craig; Lux, Michael P; Ma, Edmond S K; MacInnis, Robert J; Maishman, Tom; Makalic, Enes; Malone, Kathleen E; Kostovska, Ivana Maleva; Mannermaa, Arto; Manoukian, Siranoush; Manson, JoAnn E; Margolin, Sara; Mariapun, Shivaani; Martinez, Maria Elena; Matsuo, Keitaro; Mavroudis, Dimitrios; McKay, James; McLean, Catriona; Meijers-Heijboer, Hanne; Meindl, Alfons; Menéndez, Primitiva; Menon, Usha; Meyer, Jeffery; Miao, Hui; Miller, Nicola; Taib, Nur Aishah Mohd; Muir, Kenneth; Mulligan, Anna Marie; Mulot, Claire; Neuhausen, Susan L; Nevanlinna, Heli; Neven, Patrick; Nielsen, Sune F; Noh, Dong-Young; Nordestgaard, Børge G; Norman, Aaron; Olopade, Olufunmilayo I; Olson, Janet E; Olsson, Håkan; Olswold, Curtis; Orr, Nick; Pankratz, V Shane; Park, Sue K; Park-Simon, Tjoung-Won; Lloyd, Rachel; Perez, Jose I A; Peterlongo, Paolo; Peto, Julian; Phillips, Kelly-Anne; Pinchev, Mila; Plaseska-Karanfilska, Dijana; Prentice, Ross; Presneau, Nadege; Prokofyeva, Darya; Pugh, Elizabeth; Pylkäs, Katri; Rack, Brigitte; Radice, Paolo; Rahman, Nazneen; Rennert, Gadi; Rennert, Hedy S; Rhenius, Valerie; Romero, Atocha; Romm, Jane; Ruddy, Kathryn J; Rüdiger, Thomas; Rudolph, Anja; Ruebner, Matthias; Rutgers, Emiel J T; Saloustros, Emmanouil; Sandler, Dale P; Sangrajrang, Suleeporn; Sawyer, Elinor J; Schmidt, Daniel F; Schmutzler, Rita K; Schneeweiss, Andreas; Schoemaker, Minouk J; Schumacher, Fredrick; Schürmann, Peter; Scott, Rodney J; Scott, Christopher; Seal, Sheila; Seynaeve, Caroline; Shah, Mitul; Sharma, Priyanka; Shen, Chen-Yang; Sheng, Grace; Sherman, Mark E; Shrubsole, Martha J; Shu, Xiao-Ou; Smeets, Ann; Sohn, Christof; Southey, Melissa C; Spinelli, John J; Stegmaier, Christa; Stewart-Brown, Sarah; Stone, Jennifer; Stram, Daniel O; Surowy, Harald; Swerdlow, Anthony; Tamimi, Rulla; Taylor, Jack A; Tengström, Maria; Teo, Soo H; Beth Terry, Mary; Tessier, Daniel C; Thanasitthichai, Somchai; Thöne, Kathrin; Tollenaar, Rob A E M; Tomlinson, Ian; Tong, Ling; Torres, Diana; Truong, Thérèse; Tseng, Chiu-Chen; Tsugane, Shoichiro; Ulmer, Hans-Ulrich; Ursin, Giske; Untch, Michael; Vachon, Celine; van Asperen, Christi J; Van Den Berg, David; van den Ouweland, Ans M W; van der Kolk, Lizet; van der Luijt, Rob B; Vincent, Daniel; Vollenweider, Jason; Waisfisz, Quinten; Wang-Gohrke, Shan; Weinberg, Clarice R; Wendt, Camilla; Whittemore, Alice S; Wildiers, Hans; Willett, Walter; Winqvist, Robert; Wolk, Alicja; Wu, Anna H; Xia, Lucy; Yamaji, Taiki; Yang, Xiaohong R; Har Yip, Cheng; Yoo, Keun-Young; Yu, Jyh-Cherng; Zheng, Wei; Zheng, Ying; Zhu, Bin; Ziogas, Argyrios; Ziv, Elad; Lakhani, Sunil R; Antoniou, Antonis C; Droit, Arnaud; Andrulis, Irene L; Amos, Christopher I; Couch, Fergus J; Pharoah, Paul D P; Chang-Claude, Jenny; Hall, Per; Hunter, David J; Milne, Roger L; García-Closas, Montserrat; Schmidt, Marjanka K; Chanock, Stephen J; Dunning, Alison M; Edwards, Stacey L; Bader, Gary D; Chenevix-Trench, Georgia; Simard, Jacques; Kraft, Peter; Easton, Douglas F

    2017-11-02

    Breast cancer risk is influenced by rare coding variants in susceptibility genes, such as BRCA1, and many common, mostly non-coding variants. However, much of the genetic contribution to breast cancer risk remains unknown. Here we report the results of a genome-wide association study of breast cancer in 122,977 cases and 105,974 controls of European ancestry and 14,068 cases and 13,104 controls of East Asian ancestry. We identified 65 new loci that are associated with overall breast cancer risk at P < 5 × 10 -8 . The majority of credible risk single-nucleotide polymorphisms in these loci fall in distal regulatory elements, and by integrating in silico data to predict target genes in breast cells at each locus, we demonstrate a strong overlap between candidate target genes and somatic driver genes in breast tumours. We also find that heritability of breast cancer due to all single-nucleotide polymorphisms in regulatory features was 2-5-fold enriched relative to the genome-wide average, with strong enrichment for particular transcription factor binding sites. These results provide further insight into genetic susceptibility to breast cancer and will improve the use of genetic risk scores for individualized screening and prevention.

  10. Role of tumour necrosis factor gene polymorphisms (-308 and -238) in breast cancer susceptibility and severity

    International Nuclear Information System (INIS)

    Azmy, Iman AF; Balasubramanian, Saba P; Wilson, Anthony G; Stephenson, Timothy J; Cox, Angela; Brown, Nicola J; Reed, Malcolm WR

    2004-01-01

    Genetic polymorphisms in the promoter region of the tumour necrosis factor (TNF) gene can regulate gene expression and have been associated with inflammatory and malignant conditions. We have investigated two polymorphisms in the promoter of the TNF gene (-308 G>A and -238 G>A) for their role in breast cancer susceptibility and severity by means of an allelic association study. Using a case–control study design, breast cancer patients (n = 709) and appropriate age-matched and sex-matched controls obtained from the Breast Screening Unit (n = 498) were genotyped for these TNF polymorphisms, using a high-throughput allelic discrimination method. Allele frequencies for both polymorphisms were similar in both breast cancer cases and controls. However, the -308 polymorphism was found to be associated with vascular invasion in breast tumours (P = 0.024). Comparison with other standard prognostic indices did not show any association for either genotype. We demonstrated no association between the -308G>A polymorphism and the -238G>A polymorphism in the promoter region of TNF and susceptibility to breast cancer, in a large North European population. However, the -308 G>A polymorphism was found to be associated with the presence of vascular invasion in breast tumours

  11. Mitochondrially targeted vitamin E succinate efficiently kills breast tumour-initiating cells in a complex II-dependent manner

    International Nuclear Information System (INIS)

    Yan, Bing; Stantic, Marina; Zobalova, Renata; Bezawork-Geleta, Ayenachew; Stapelberg, Michael; Stursa, Jan; Prokopova, Katerina; Dong, Lanfeng; Neuzil, Jiri

    2015-01-01

    Accumulating evidence suggests that breast cancer involves tumour-initiating cells (TICs), which play a role in initiation, metastasis, therapeutic resistance and relapse of the disease. Emerging drugs that target TICs are becoming a focus of contemporary research. Mitocans, a group of compounds that induce apoptosis of cancer cells by destabilising their mitochondria, are showing their potential in killing TICs. In this project, we investigated mitochondrially targeted vitamin E succinate (MitoVES), a recently developed mitocan, for its in vitro and in vivo efficacy against TICs. The mammosphere model of breast TICs was established by culturing murine NeuTL and human MCF7 cells as spheres. This model was verified by stem cell marker expression, tumour initiation capacity and chemotherapeutic resistance. Cell susceptibility to MitoVES was assessed and the cell death pathway investigated. In vivo efficacy was studied by grafting NeuTL TICs to form syngeneic tumours. Mammospheres derived from NeuTL and MCF7 breast cancer cells were enriched in the level of stemness, and the sphere cells featured altered mitochondrial function. Sphere cultures were resistant to several established anti-cancer agents while they were susceptible to MitoVES. Killing of mammospheres was suppressed when the mitochondrial complex II, the molecular target of MitoVES, was knocked down. Importantly, MitoVES inhibited progression of syngeneic HER2 high tumours derived from breast TICs by inducing apoptosis in tumour cells. These results demonstrate that using mammospheres, a plausible model for studying TICs, drugs that target mitochondria efficiently kill breast tumour-initiating cells. The online version of this article (doi:10.1186/s12885-015-1394-7) contains supplementary material, which is available to authorized users

  12. Targeting Chromosomal Instability and Tumour Heterogeneity in HER2-Positive Breast Cancer

    DEFF Research Database (Denmark)

    Burrell, Rebecca A.; Birkbak, Nicolai Juul; Johnston, Stephen R.

    2010-01-01

    Chromosomal instability (CIN) is a common cause of tumour heterogeneity and poor prognosis in solid tumours and describes cell-cell variation in chromosome structure or number across a tumour population. In this article we consider evidence suggesting that CIN may be targeted and may influence...... response to distinct chemotherapy regimens, using HER2-positive breast cancer as an example. Pre-clinical models have indicated a role for HER2 signalling in initiating CIN and defective cell-cycle control, and evidence suggests that HER2-targeting may attenuate this process. Anthracyclines and platinum...... agents may target tumours with distinct patterns of karyotypic complexity, whereas taxanes may have preferential activity in tumours with relative chromosomal stability. A greater understanding of karyotypic complexity and identification of methods to directly examine and target CIN may support novel...

  13. Higher serum concentrations of vimentin and DAKP1 are associated with aggressive breast tumour phenotypes in Ghanaian women.

    Science.gov (United States)

    Arko-Boham, Benjamin; Lomotey, Justice Tanihu; Tetteh, Emmanuel Nomo; Tagoe, Emmanuel Ayitey; Aryee, Nii Ayite; Owusu, Ewurama Ampadu; Okai, Isaac; Blay, Richard Michael; Clegg-Lamptey, Joe-Nat

    2017-01-01

    Breast cancer, the most commonly diagnosed cancer among women and leading cause of cancer-related deaths worldwide, exhibits aggressive behavior in indigenous African women evidenced by high histologic grade tumours with low hormone receptor positivity. Aggressive breast cancers grow quickly, easily metastasize and recur and often have unfavourable outcomes. The current study investigated candidate genes that may regulate tumour aggression in Ghanaian women. We hypothesize that increased expression and function of certain genes other than the widely-held view attributing breast cancer aggression in African populations to their younger population age may be responsible for the aggressive nature of tumours. Employing ELISA, we assayed for vimentin and death-associated protein kinase 1 (DAPK1) from thawed archived (stored at -80 °C) serum samples obtained from 40 clinically confirmed Ghanaian breast cancer patients and 40 apparently healthy controls. Patients' clinical records and tumour parameters matching the samples were retrieved from the database of the hospital. ANOVA was used to compare means of serum protein concentration among groups while Chi-square analysis was used for the categorical data sets with p -value ≤0.05 considered significant. Multiple logistic regression analysis was conducted to determine the association between protein concentration and tumour parameters. Of the 80 samples, 27 (33.8%) and 53 (66.2%) were from young (<35 years) and old (≥35 years), respectively. Vimentin and DAPK1 concentration were higher in patients than controls with higher levels in "young" age group than "old" age group. Vimentin concentration was highest in grade 3 tumours followed by grade 2 and 1 but that for DAPK1 was not significant. For vimentin, tumour area strongly correlated with tumour grade ( r  = 0.696, p  < 0.05) but weakly correlated with tumour stage ( r  = 0.420, p  < 0.05). Patient's age correlated with DAPK1 concentration ( r  = 0

  14. TOX3 mutations in breast cancer.

    Directory of Open Access Journals (Sweden)

    James Owain Jones

    Full Text Available TOX3 maps to 16q12, a region commonly lost in breast cancers and recently implicated in the risk of developing breast cancer. However, not much is known of the role of TOX3 itself in breast cancer biology. This is the first study to determine the importance of TOX3 mutations in breast cancers. We screened TOX3 for mutations in 133 breast tumours and identified four mutations (three missense, one in-frame deletion of 30 base pairs in six primary tumours, corresponding to an overall mutation frequency of 4.5%. One potentially deleterious missense mutation in exon 3 (Leu129Phe was identified in one tumour (genomic DNA and cDNA. Whilst copy number changes of 16q12 are common in breast cancer, our data show that mutations of TOX3 are present at low frequency in tumours. Our results support that TOX3 should be further investigated to elucidate its role in breast cancer biology.

  15. Shear-wave elastography contributes to accurate tumour size estimation when assessing small breast cancers

    International Nuclear Information System (INIS)

    Mullen, R.; Thompson, J.M.; Moussa, O.; Vinnicombe, S.; Evans, A.

    2014-01-01

    Aim: To assess whether the size of peritumoural stiffness (PTS) on shear-wave elastography (SWE) for small primary breast cancers (≤15 mm) was associated with size discrepancies between grey-scale ultrasound (GSUS) and final histological size and whether the addition of PTS size to GSUS size might result in more accurate tumour size estimation when compared to final histological size. Materials and methods: A retrospective analysis of 86 consecutive patients between August 2011 and February 2013 who underwent breast-conserving surgery for tumours of size ≤15 mm at ultrasound was carried out. The size of PTS stiffness was compared to mean GSUS size, mean histological size, and the extent of size discrepancy between GSUS and histology. PTS size and GSUS were combined and compared to the final histological size. Results: PTS of >3 mm was associated with a larger mean final histological size (16 versus 11.3 mm, p < 0.001). PTS size of >3 mm was associated with a higher frequency of underestimation of final histological size by GSUS of >5 mm (63% versus 18%, p < 0.001). The combination of PTS and GSUS size led to accurate estimation of the final histological size (p = 0.03). The size of PTS was not associated with margin involvement (p = 0.27). Conclusion: PTS extending beyond 3 mm from the grey-scale abnormality is significantly associated with underestimation of tumour size of >5 mm for small invasive breast cancers. Taking into account the size of PTS also led to accurate estimation of the final histological size. Further studies are required to assess the relationship of the extent of SWE stiffness and margin status. - Highlights: • Peritumoural stiffness of greater than 3 mm was associated with larger tumour size. • Underestimation of tumour size by ultrasound was associated with peri-tumoural stiffness size. • Combining peri-tumoural stiffness size to ultrasound produced accurate tumour size estimation

  16. Classification of breast tumour using electrical impedance and machine learning techniques.

    Science.gov (United States)

    Al Amin, Abdullah; Parvin, Shahnaj; Kadir, M A; Tahmid, Tasmia; Alam, S Kaisar; Siddique-e Rabbani, K

    2014-06-01

    When a breast lump is detected through palpation, mammography or ultrasonography, the final test for characterization of the tumour, whether it is malignant or benign, is biopsy. This is invasive and carries hazards associated with any surgical procedures. The present work was undertaken to study the feasibility for such characterization using non-invasive electrical impedance measurements and machine learning techniques. Because of changes in cell morphology of malignant and benign tumours, changes are expected in impedance at a fixed frequency, and versus frequency of measurement. Tetrapolar impedance measurement (TPIM) using four electrodes at the corners of a square region of sides 4 cm was used for zone localization. Data of impedance in two orthogonal directions, measured at 5 and 200 kHz from 19 subjects, and their respective slopes with frequency were subjected to machine learning procedures through the use of feature plots. These patients had single or multiple tumours of various types in one or both breasts, and four of them had malignant tumours, as diagnosed by core biopsy. Although size and depth of the tumours are expected to affect the measurements, this preliminary work ignored these effects. Selecting 12 features from the above measurements, feature plots were drawn for the 19 patients, which displayed considerable overlap between malignant and benign cases. However, based on observed qualitative trend of the measured values, when all the feature values were divided by respective ages, the two types of tumours separated out reasonably well. Using K-NN classification method the results obtained are, positive prediction value: 60%, negative prediction value: 93%, sensitivity: 75%, specificity: 87% and efficacy: 84%, which are very good for such a test on a small sample size. Study on a larger sample is expected to give confidence in this technique, and further improvement of the technique may have the ability to replace biopsy.

  17. Classification of breast tumour using electrical impedance and machine learning techniques

    International Nuclear Information System (INIS)

    Amin, Abdullah Al; Parvin, Shahnaj; Kadir, M A; Tahmid, Tasmia; Alam, S Kaisar; Siddique-e Rabbani, K

    2014-01-01

    When a breast lump is detected through palpation, mammography or ultrasonography, the final test for characterization of the tumour, whether it is malignant or benign, is biopsy. This is invasive and carries hazards associated with any surgical procedures. The present work was undertaken to study the feasibility for such characterization using non-invasive electrical impedance measurements and machine learning techniques. Because of changes in cell morphology of malignant and benign tumours, changes are expected in impedance at a fixed frequency, and versus frequency of measurement. Tetrapolar impedance measurement (TPIM) using four electrodes at the corners of a square region of sides 4 cm was used for zone localization. Data of impedance in two orthogonal directions, measured at 5 and 200 kHz from 19 subjects, and their respective slopes with frequency were subjected to machine learning procedures through the use of feature plots. These patients had single or multiple tumours of various types in one or both breasts, and four of them had malignant tumours, as diagnosed by core biopsy. Although size and depth of the tumours are expected to affect the measurements, this preliminary work ignored these effects. Selecting 12 features from the above measurements, feature plots were drawn for the 19 patients, which displayed considerable overlap between malignant and benign cases. However, based on observed qualitative trend of the measured values, when all the feature values were divided by respective ages, the two types of tumours separated out reasonably well. Using K-NN classification method the results obtained are, positive prediction value: 60%, negative prediction value: 93%, sensitivity: 75%, specificity: 87% and efficacy: 84%, which are very good for such a test on a small sample size. Study on a larger sample is expected to give confidence in this technique, and further improvement of the technique may have the ability to replace biopsy. (paper)

  18. [Assessment of current eating habits in women diagnosed with breast tumours and changes introduced after diagnosis].

    Science.gov (United States)

    Kucharska, Alicja; Królikowska, Ewa; Sińska, Beata

    Intrroduction: Incorrect eating habits are a significant risk factor for breast tumours. An appropriate diet is a vital part in the treatment of such a disorder. The aim of the study was to assess current eating habits in women diagnosed with breast tumours and the changes introduced after diagnosis. The survey was conducted among 200 women aged 59±11.2 with a diagnosed breast tumour. An original survey questionnaire was used to assess the respondents' dietary habits. Questions pertained to the frequency of consumption of certain food groups, changes in diet since the moment of diagnosis and sources of knowledge about nutrition. A number of current incorrect eating habits became apparent (namely, low frequency of eating wholemeal products, legumes, fish, vegetables, fruit and high frequency of eating sweets), as well as many beneficial changes introduced after the diagnosis (more frequent consumption of wholemeal products, poultry, vegetables and fruit and lower frequency of consumption of red meat, meat preserves, sweets, sweetened drinks and alcohol), with no difference in age, education or time elapsed since the diagnosis. Less than one third of respondents have received nutrition advice after their diagnosis. In spite of the beneficial changes in dietary habits there is a need for widely available, reliable nutrition education amongst all women diagnosed with a breast tumour.

  19. Lymphoscintigraphy and SPECT/CT in multicentric and multifocal breast cancer: does each tumour have a separate drainage pattern? Results of a Dutch multicentre study (MULTISENT)

    Energy Technology Data Exchange (ETDEWEB)

    Brouwer, O.R. [Antoni van Leeuwenhoek Hospital, Department of Nuclear Medicine, Netherlands Cancer Institute, Amsterdam (Netherlands); Antoni van Leeuwenhoekhospital, Amsterdam (Netherlands); Vermeeren, L.; Valdes Olmos, R.A. [Antoni van Leeuwenhoek Hospital, Department of Nuclear Medicine, Netherlands Cancer Institute, Amsterdam (Netherlands); Ploeg, I.M.C. van der; Rutgers, E.J.T.; Oldenburg, H.S.A. [Antoni van Leeuwenhoek Hospital, Department of Surgery, Netherlands Cancer Institute, Amsterdam (Netherlands); Loo, C.E. [Antoni van Leeuwenhoek Hospital, Department of Radiology, Netherlands Cancer Institute, Amsterdam (Netherlands); Pereira-Bouda, L.M.; Smit, F. [Rijnland Hospital, Department of Nuclear Medicine, Leiderdorp (Netherlands); Neijenhuis, P. [Rijnland Hospital, Department of Surgery, Leiderdorp (Netherlands); Vrouenraets, B.C. [Sint Lucas Andreas Hospital, Department of Surgery, Amsterdam (Netherlands); Sivro-Prndelj, F. [Sint Lucas Andreas Hospital, Department of Nuclear Medicine, Amsterdam (Netherlands); Jap-a-Joe, S.M.; Borgstein, P.J. [Onze Lieve Vrouwe Gasthuis, Department of Nuclear Medicine, Amsterdam (Netherlands)

    2012-07-15

    To investigate whether lymphoscintigraphy and SPECT/CT after intralesional injection of radiopharmaceutical into each tumour separately in patients with multiple malignancies in one breast yields additional sentinel nodes compared to intralesional injection of the largest tumour only. Patients were included prospectively at four centres in The Netherlands. Lymphatic flow was studied using planar lymphoscintigraphy and SPECT/CT until 4 h after administration of {sup 99m}Tc-nanocolloid in the largest tumour. Subsequently, the smaller tumour(s) was injected intratumorally followed by the same imaging sequence. Sentinel nodes were intraoperatively localized using a gamma ray detection probe and vital blue dye. Included in the study were 50 patients. Additional lymphatic drainage was depicted after the second and/or third injection in 32 patients (64 %). Comparison of planar images and SPECT/CT images after consecutive injections enabled visualization of the number and location of additional sentinel nodes (32 axillary, 11 internal mammary chain, 2 intramammary, and 1 interpectoral. A sentinel node contained metastases in 17 patients (34 %)). In five patients with a tumour-positive node in the axilla that was visualized after the first injection, an additional involved axillary node was found after the second injection. In two patients, isolated tumour cells were found in sentinel nodes that were only visualized after the second injection, whilst the sentinel nodes identified after the first injection were tumour-negative. Lymphoscintigraphy and SPECT/CT after consecutive intratumoral injections of tracer enable lymphatic mapping of each tumour separately in patients with multiple malignancies within one breast. The high incidence of additional sentinel nodes draining from tumours other than the largest one suggests that separate tumour-related tracer injections may be a more accurate approach to mapping and sampling of sentinel nodes in patients with multicentric or

  20. Lymphoscintigraphy and SPECT/CT in multicentric and multifocal breast cancer: does each tumour have a separate drainage pattern? Results of a Dutch multicentre study (MULTISENT).

    Science.gov (United States)

    Brouwer, O R; Vermeeren, L; van der Ploeg, I M C; Valdés Olmos, R A; Loo, C E; Pereira-Bouda, L M; Smit, F; Neijenhuis, P; Vrouenraets, B C; Sivro-Prndelj, F; Jap-a-Joe, S M; Borgstein, P J; Rutgers, E J Th; Oldenburg, H S A

    2012-07-01

    To investigate whether lymphoscintigraphy and SPECT/CT after intralesional injection of radiopharmaceutical into each tumour separately in patients with multiple malignancies in one breast yields additional sentinel nodes compared to intralesional injection of the largest tumour only. Patients were included prospectively at four centres in The Netherlands. Lymphatic flow was studied using planar lymphoscintigraphy and SPECT/CT until 4 h after administration of (99m)Tc-nanocolloid in the largest tumour. Subsequently, the smaller tumour(s) was injected intratumorally followed by the same imaging sequence. Sentinel nodes were intraoperatively localized using a gamma ray detection probe and vital blue dye. Included in the study were 50 patients. Additional lymphatic drainage was depicted after the second and/or third injection in 32 patients (64%). Comparison of planar images and SPECT/CT images after consecutive injections enabled visualization of the number and location of additional sentinel nodes (32 axillary, 11 internal mammary chain, 2 intramammary, and 1 interpectoral. A sentinel node contained metastases in 17 patients (34%). In five patients with a tumour-positive node in the axilla that was visualized after the first injection, an additional involved axillary node was found after the second injection. In two patients, isolated tumour cells were found in sentinel nodes that were only visualized after the second injection, whilst the sentinel nodes identified after the first injection were tumour-negative. Lymphoscintigraphy and SPECT/CT after consecutive intratumoral injections of tracer enable lymphatic mapping of each tumour separately in patients with multiple malignancies within one breast. The high incidence of additional sentinel nodes draining from tumours other than the largest one suggests that separate tumour-related tracer injections may be a more accurate approach to mapping and sampling of sentinel nodes in patients with multicentric or

  1. Can breast cancer patients with HER2 dual-equivocal tumours be managed as HER2-negative disease?

    Science.gov (United States)

    Tong, Yiwei; Chen, Xiaosong; Fei, Xiaochun; Lin, Lin; Wu, Jiayi; Huang, Ou; He, Jianrong; Zhu, Li; Chen, Weiguo; Li, Yafen; Shen, Kunwei

    2018-01-01

    Increasing human epidermal growth factor receptor 2 (HER2) immunohistochemistry (IHC)/fluorescence in situ hybridisation (FISH) dual-equivocal breast tumours are reported after the 2013 American Society of Clinical Oncology/College of American Pathologists (ASCO/CAP) guideline update. The aim of this study is to investigate the clinico-pathologic characteristics, treatment patterns and disease outcome of these patients with HER2 dual-equivocal tumours. Patients with HER2 IHC 2+ and available FISH results were retrospectively analysed from the Comprehensive Breast Health Center, Shanghai Ruijin Hospital. The 2013 ASCO/CAP guideline was applied to define HER2-positive, dual-equivocal and -negative groups. Patient characteristics, systemic treatment patterns and survival were compared among these groups. Reverse transcriptase-polymerase chain reaction-based assays were applied to test HER2 mRNA expression level. Among 691 patients included, 133 (19.25%) were HER2 positive, 25 (3.62%) were HER2 dual-equivocal and 533 (77.13%) were HER2 negative. Univariate and multivariate analyses stated that HER2 dual-equivocal tumours shared more similarity with HER2-negative tumours, whereas HER2-positive tumours had rather different clinico-pathologic features. HER2 dual-equivocal tumours had similar HER2 mRNA levels compared with HER2-negative tumours (P = 0.26), which were much less compared with HER2-positive breast cancer. Besides, adjuvant systemic treatment patterns were comparable between HER2-negative and dual-equivocal tumours, and none of HER2 dual-equivocal patients received anti-HER2 treatment. There was no survival difference among these three groups (P = 0.43). HER2 dual-equivocal tumours share more similarity with HER2-negative disease in terms of clinico-pathologic features, HER2 mRNA levels, adjuvant systemic treatment patterns and disease outcome, which deserves further clinical evaluation. Copyright © 2017 Elsevier Ltd. All rights reserved.

  2. Near-infrared laser, time domain, breast tumour detection system

    International Nuclear Information System (INIS)

    Joblin, A.J.

    1996-01-01

    image resolution using this technique is poor, being worse that S mm, with currently available time resolved detection system capabilities. However it was also found that tumour bodies smaller in size than the system resolution parameter produced a measurable change in the signal, which could be used to detect small tumour bodies. So while high resolution images of the breast are not possible, simple measurements to detect the presence of breast disease may be possible. This will require further work to allow the signal from breast disease to be distinguished without error from the expected variations in signal due to the variability in normal breast characteristics

  3. Surveillance of women with a personal history of breast cancer by tumour subtype.

    Science.gov (United States)

    Benveniste, A P; Dryden, M J; Bedrosian, I; Morrow, P K; Bassett, R L; Yang, W

    2017-03-01

    To determine if the rate and timing of a second breast cancer event (SBCE) in women with a personal history of breast cancer varies by disease subtype or breast imaging method. A retrospective review was performed of women with a SBCE from January 2006 to December 2010 at a single institution. Data analysed included oestrogen receptor (ER), progesterone receptor (PR), human epidermal growth factor receptor 2 (HER2) status of the primary and second breast cancers; mammographic and ultrasound (US) features from SBCE; and the time interval between both events. Of 207 patients diagnosed with a SBCE, the median age at first diagnosis was 50.6 years, range 24.8 to 80.2; at second diagnosis was 56.2 years, range 25.8 to 87.9. Eleven percent of SBCE were diagnosed >10 years after the primary cancer diagnosis. The median time between the first and second diagnosis for ER-positive patients was 2.7 years (range 0.7-17.4 years); and 1.9 years for ER-negative patients, (range 0.4-23.4 years; pbreast cancer (TNBC) had a shorter time between diagnoses than others (p=0.0003). At 3, 5, and 10 years, 85%, 92%, and 97% of ER-negative and 54%, 81%, and 95% of ER-positive tumours, respectively, had recurred. ER-negative tumours and TNBC were more likely to be visible at US. There may be a role for customised imaging surveillance of women with a personal history of breast cancer (PHBC) after 10 years. Further studies are necessary to determine if US may be valuable in the surveillance of patients with ER-negative and TNBC tumours. Copyright © 2016 The Royal College of Radiologists. Published by Elsevier Ltd. All rights reserved.

  4. Evaluation of tumour markers as differential diagnostic tool in patients with suspicion of liver metastases from breast cancer.

    Science.gov (United States)

    Liska, Vaclav; Holubec, Lubos; Treska, Vladislav; Vrzalova, Jindra; Skalicky, Tomas; Sutnar, Alan; Kormunda, Stanislav; Bruha, Jan; Vycital, Ondrej; Finek, Jindrich; Pesta, Martin; Pecen, Ladislav; Topolcan, Ondrej

    2011-04-01

    The liver is the site of breast cancer metastasis in 50% of patients with advanced disease. Tumour markers have been demonstrated as being useful in follow-up of patients with breast cancer, in early detection of recurrence of breast cancer after radical surgical treatments, and in assessing oncologic therapy effect, but no study has been carried out on their usefullness in distinguishing benign liver lesions from breast cancer metastases. The aim of this study was therefore to evaluate the importance of tumour markers carcinoembryonic antigen (CEA), carbohydrate antigen CA19-9 (CA19-9), thymidine kinase (TK), tissue polypeptide antigen (TPA), tissue polypeptide-specific antigen (TPS) and cytokeratin 19 fragment (CYFRA 21-1) in differential diagnosis between benign liver lesions and liver metastases of breast cancer. The study includes 3 groups: 22 patients with liver metastases of breast cancer; 39 patients with benign liver lesions (hemangioma, focal nodular hyperplasia, liver cyst, hepatocellular adenoma); and 21 patients without any liver disease or lesion that were operated on for benign extrahepatic diseases (groin hernia, varices of lower limbs) as a control group. The serum levels of tumour markers were assessed by means of immunoanalytical methods. Preoperative serum levels of CYFRA 21-1, TPA, TPS and CEA were significantly higher in patients with liver metastases of breast cancer in contrast to healthy controls and patients with benign liver lesions (p-value<0.05). Serum levels of CA19-9 and TK were higher in patients with malignancy in comparison with benign liver disease and healthy controls but these differences were not statistically significant. Tumour markers CEA, CYFRA 21-1, TPA and TPS can be recommended as a good tool for differential diagnosis between liver metastases of breast cancer and benign liver lesions.

  5. Which factors influence MRI-pathology concordance of tumour size measurements in breast cancer?

    Energy Technology Data Exchange (ETDEWEB)

    Rominger, M.; Frauenfelder, T. [University Hospital Zurich, Institute of Diagnostic and Interventional Radiology, Zurich (Switzerland); Berg, D. [Urbankrankenhaus Berlin, Anesthesiology, Berlin (Germany); Ramaswamy, A. [University Hospital Marburg, Pathology, Marburg (Germany); Timmesfeld, N. [Philipps University Marburg, Institute for Medical Biometry and Epidemiology, Marburg (Germany)

    2016-05-15

    To assess MRI-pathology concordance and factors influencing tumour size measurement in breast cancer. MRI tumour size (greatest diameter in anatomical planes (MRI-In-Plane) and greatest diameter along main tumour axis (MRI-MPR)) of 115 consecutive breast lesions (59 invasive lobular carcinoma, 46 invasive ductal carcinoma, and 10 ductal carcinoma in situ) was retrospectively compared to size measured at histopathology (pT size (Path-TNM) and greatest tumour diameter as relevant for excision (Path-Diameter; reference standard)). Histopathological tumour types, preoperative palpability, surgical management, additional high-risk lesions, and BI-RADS lesion type (mass versus non-mass enhancements) were assessed as possible influencing factors. Systematic errors were most pronounced between MRI-MPR and Path-TNM (7.1 mm, limits of agreement (LoA) [-21.7; 35.9]), and were lowest between MRI-In-Plane and Path-Diameter (0.2 mm, LoA [-19.7; 20.1]). Concordance rate of MRI-In-Plane with Path-Diameter was 86 % (97/113), overestimation 9 % (10/113) and underestimation 5 % (6/113); BI-RADS mass lesions were overestimated in 7 % (6/81) versus 41 % (13/32) for non-mass enhancements. On multivariate analysis only BI-RADS lesion type significantly influenced MRI-pathology concordance (p < 0.001). 2/59 (3 %) ILC did not enhance. Concordance rate varies according to the execution of MRI and histopathological measurements. Beyond this only non-mass enhancement significantly predicted discordance. (orig.)

  6. Gene expression of circulating tumour cells and its correlation with tumour stage in breast cancer patients

    Directory of Open Access Journals (Sweden)

    Bölke E

    2009-09-01

    Full Text Available Abstract Background Breast cancer (BC represents one of the leading causes of cancer related deaths worldwide. New tools for diagnostic staging and therapeutic monitoring are needed to improve individualized therapies and improve clinical outcome. The analyses of circulating tumour cells may provide important prognostic information in the clinical setting. Materials and methods Circulating tumour cells (CTC of 63 BC patients were isolated from peripheral blood (PB through immunomagnetic separation. Subsequently, RT-PCR or mPCR for the genes ga733.2, muc-1, c-erbB2, mgb-1, spdef and c-erbB2 were performed. Subsequently, expression data were correlated with the tumour stages. Fourteen healthy individuals served as controls. Results Significant correlations with tumour stages were found in single gene analyses of ga733.2, muc-1 and in multi-gene analyses of ga733.2/muc-1/mgb1/spdef. Furthermore, a significant correlation of Ca 15-3 and all studied genes was also observed. Conclusion Herein, we demonstrated a positive correlation of a gene signature consisting of ga733.2, muc-1, mgb1 and spdef and advanced stages of BC. Moreover, all studied genes and gene patterns revealed a significant correlation with Ca 15-3 positive cases.

  7. EPHB6 augments both development and drug sensitivity of triple-negative breast cancer tumours.

    Science.gov (United States)

    Toosi, Behzad M; El Zawily, Amr; Truitt, Luke; Shannon, Matthew; Allonby, Odette; Babu, Mohan; DeCoteau, John; Mousseau, Darrell; Ali, Mohsin; Freywald, Tanya; Gall, Amanda; Vizeacoumar, Frederick S; Kirzinger, Morgan W; Geyer, C Ronald; Anderson, Deborah H; Kim, TaeHyung; Welm, Alana L; Siegel, Peter; Vizeacoumar, Franco J; Kusalik, Anthony; Freywald, Andrew

    2018-04-27

    Triple-negative breast cancer (TNBC) tumours that lack expression of oestrogen, and progesterone receptors, and do not overexpress the HER2 receptor represent the most aggressive breast cancer subtype, which is characterised by the resistance to therapy in frequently relapsing tumours and a high rate of patient mortality. This is likely due to the resistance of slowly proliferating tumour-initiating cells (TICs), and understanding molecular mechanisms that control TICs behaviour is crucial for the development of effective therapeutic approaches. Here, we present our novel findings, indicating that an intrinsically catalytically inactive member of the Eph group of receptor tyrosine kinases, EPHB6, partially suppresses the epithelial-mesenchymal transition in TNBC cells, while also promoting expansion of TICs. Our work reveals that EPHB6 interacts with the GRB2 adapter protein and that its effect on enhancing cell proliferation is mediated by the activation of the RAS-ERK pathway, which allows it to elevate the expression of the TIC-related transcription factor, OCT4. Consistent with this, suppression of either ERK or OCT4 activities blocks EPHB6-induced pro-proliferative responses. In line with its ability to trigger propagation of TICs, EPHB6 accelerates tumour growth, potentiates tumour initiation and increases TIC populations in xenograft models of TNBC. Remarkably, EPHB6 also suppresses tumour drug resistance to DNA-damaging therapy, probably by forcing TICs into a more proliferative, drug-sensitive state. In agreement, patients with higher EPHB6 expression in their tumours have a better chance for recurrence-free survival. These observations describe an entirely new mechanism that governs TNBC and suggest that it may be beneficial to enhance EPHB6 action concurrent with applying a conventional DNA-damaging treatment, as it would decrease drug resistance and improve tumour elimination.

  8. Pharmacoeconomics of bisphosphonates for skeletal-related event prevention in metastatic non-breast solid tumours.

    Science.gov (United States)

    Carter, John A; Joshi, Avani D; Kaura, Satyin; Botteman, Marc F

    2012-05-01

    Bisphosphonates reduce the risk of skeletal-related events (SREs; i.e. spinal cord compression, pathological fracture, radiation or surgery to the bone, and hypercalcaemia) in patients with metastatic cancer. A number of analyses have been conducted to assess the cost effectiveness of bisphosphonates in patients with bone metastases secondary to breast cancer, but few in other solid tumours. This is a review of cost-effectiveness analyses in patients with non-breast solid tumours and bone metastases. A literature search was conducted to identify cost-effectiveness analyses reporting the cost per QALY gained of bisphosphonates in patients with metastatic bone disease secondary to non-breast solid tumours. Four analyses met inclusion criteria. These included two in prostate cancer (one of which used a global perspective but expressed results in $US, and the other reported from a multiple country perspective: France, Germany, Portugal and the Netherlands). The remaining analyses were in lung cancer (in the UK, France, Germany, Portugal and the Netherlands), and renal cell carcinoma (in the UK, France and Germany). In each analysis, the cost effectiveness of zoledronic acid versus placebo was analysed. Zoledronic acid was found to be cost effective in all European countries across all three indications but not in the sole global prostate cancer analysis. Across countries and indications, assumptions regarding patient survival, drug cost and baseline utility (i.e. patient utility with metastatic disease but without an SRE) were the most robust drivers of modelled estimates. Assumptions of SRE-related costs were most often the second strongest cost driver. Further review indicated that particular attention should be paid to the inclusion or exclusion of nonsignificant survival benefits, whether health state utilities were elicited from community or patient samples or author assumptions, delineation between symptomatic and asymptomatic SREs, and the methods with which SRE

  9. Translation elongation factor eEF1A2 is a potential oncoprotein that is overexpressed in two-thirds of breast tumours

    International Nuclear Information System (INIS)

    Tomlinson, Victoria AL; Newbery, Helen J; Wray, Naomi R; Jackson, Juliette; Larionov, Alexey; Miller, William R; Dixon, J Michael; Abbott, Catherine M

    2005-01-01

    The tissue-specific translation elongation factor eEF1A2 was recently shown to be a potential oncogene that is overexpressed in ovarian cancer. Although there is no direct evidence for an involvement of eEF1A2 in breast cancer, the genomic region to which EEF1A2 maps, 20q13, is frequently amplified in breast tumours. We therefore sought to establish whether eEF1A2 expression might be upregulated in breast cancer. eEF1A2 is highly similar (98%) to the near-ubiquitously expressed eEF1A1 (formerly known as EF1-α) making analysis with commercial antibodies difficult. We have developed specific anti-eEF1A2 antibodies and used them in immunohistochemical analyses of tumour samples. We report the novel finding that although eEF1A2 is barely detectable in normal breast it is moderately to strongly expressed in two-thirds of breast tumours. This overexpression is strongly associated with estrogen receptor positivity. eEF1A2 should be considered as a putative oncogene in breast cancer that may be a useful diagnostic marker and therapeutic target for a high proportion of breast tumours. The oncogenicity of eEF1A2 may be related to its role in protein synthesis or to its potential non-canonical functions in cytoskeletal remodelling or apoptosis

  10. Promoter methylation-associated loss of ID4 expression is a marker of tumour recurrence in human breast cancer

    International Nuclear Information System (INIS)

    Noetzel, Erik; Veeck, Jürgen; Niederacher, Dieter; Galm, Oliver; Horn, Felicitas; Hartmann, Arndt; Knüchel, Ruth; Dahl, Edgar

    2008-01-01

    Inhibitor of DNA binding/Inhibitor of differentiation 4 (ID4) is a critical factor for cell proliferation and differentiation in normal vertebrate development. ID4 has regulative functions for differentiation and growth of the developing brain. The role of ID1, ID2 and ID3 are expected to be oncogenic due to their overexpression in pancreatic cancer and colorectal adenocarcinomas, respectively. Aside from these findings, loss of ID3 expression was demonstrated in ovarian cancer. The aim of the present study was to reveal the factual role of ID4 in carcinogenesis in more detail, since its role for the pathogenesis of human breast cancer has been discussed controversially, assigning both oncogenic and tumour suppressive functions. ID4 promoter methylation, ID4 mRNA expression and ID4 protein expression were analysed in primary human breast cancer specimens using methylation-specific PCR (MSP) (n=170), semiquantitative realtime RT-PCR (n=46) and immunhistochemistry (n=3), respectively. In order to demonstrate a functional association of ID4 promoter methylation with its gene silencing, we performed DNA demethylation analysis with four human breast cell lines using MSP and semiquantitative realtime RT-PCR. In addition, we performed correlations of ID4 promoter methylation with ID4 mRNA and ID4 protein expression in matched samples of breast tumour and corresponding normal tissue. We carried out statistical analyses in order to find correlations between ID4 promoter methylation and clinicopathological parameters. Frequent ID4 promoter methylation was observed in primary breast cancer samples (69%, 117/170). We found a tight correlation (P<0.0001) between ID4 promoter methylation and loss of ID4 expression in primary breast cancer 3 specimens. Demethylating treatment with breast cancer cell lines was associated with clear ID4 mRNA re-expression. Tumours with ID4 promoter methylation showed distinct loss of ID4 expression on both transcription and protein level

  11. Targeting of breast metastases using a viral gene vector with tumour-selective transcription.

    LENUS (Irish Health Repository)

    Rajendran, Simon

    2012-01-31

    BACKGROUND: Adeno-associated virus (AAV) vectors have significant potential as gene delivery vectors for cancer gene therapy. However, broad AAV2 tissue tropism results in nonspecific gene expression. MATERIALS AND METHODS: We investigated use of the C-X-C chemokine receptor type 4 (CXCR4) promoter to restrict AAV expression to tumour cells, in subcutaneous MCF-7 xenograft mouse models of breast cancer and in patient samples, using bioluminescent imaging and flow cytometric analysis. RESULTS: Higher transgene expression levels were observed in subcutaneous MCF-7 tumours relative to normal tissue (muscle) using the CXCR4 promoter, unlike a ubiquitously expressing Cytomegalovirus promoter construct, with preferential AAVCXCR4 expression in epithelial tumour and CXCR4-positive cells. Transgene expression following intravenously administered AAVCXCR4 in a model of liver metastasis was detected specifically in livers of tumour bearing mice. Ex vivo analysis using patient samples also demonstrated higher AAVCXCR4 expression in tumour compared with normal liver tissue. CONCLUSION: This study demonstrates for the first time, the potential for systemic administration of AAV2 vector for tumour-selective gene therapy.

  12. Targeting multiple cannabinoid anti-tumour pathways with a resorcinol derivative leads to inhibition of advanced stages of breast cancer.

    Science.gov (United States)

    Murase, Ryuichi; Kawamura, Rumi; Singer, Eric; Pakdel, Arash; Sarma, Pranamee; Judkins, Jonathon; Elwakeel, Eiman; Dayal, Sonali; Martinez-Martinez, Esther; Amere, Mukkanti; Gujjar, Ramesh; Mahadevan, Anu; Desprez, Pierre-Yves; McAllister, Sean D

    2014-10-01

    The psychoactive cannabinoid Δ(9) -tetrahydrocannabinol (THC) and the non-psychoactive cannabinoid cannabidiol (CBD) can both reduce cancer progression, each through distinct anti-tumour pathways. Our goal was to discover a compound that could efficiently target both cannabinoid anti-tumour pathways. To measure breast cancer cell proliferation/viability and invasion, MTT and Boyden chamber assays were used. Modulation of reactive oxygen species (ROS) and apoptosis was measured using dichlorodihydrofluorescein and annexin/propidium iodide, respectively, in combination with cell flow cytometry. Changes in protein levels were evaluated using Western analysis. Orthotopic and i.v. mouse models of breast cancer metastasis were used to test the activity of cannabinoids in vivo. CBD reduced breast cancer metastasis in advanced stages of the disease as the direct result of down-regulating the transcriptional regulator Id1. However, this was associated with moderate increases in survival. We therefore screened for analogues that could co-target cannabinoid anti-tumour pathways (CBD- and THC-associated) and discovered the compound O-1663. This analogue inhibited Id1, produced a marked stimulation of ROS, up-regulated autophagy and induced apoptosis. Of all the compounds tested, it was the most potent at inhibiting breast cancer cell proliferation and invasion in culture and metastasis in vivo. O-1663 prolonged survival in advanced stages of breast cancer metastasis. Developing compounds that can simultaneously target multiple cannabinoid anti-tumour pathways efficiently may provide a novel approach for the treatment of patients with metastatic breast cancer. © 2014 The British Pharmacological Society.

  13. Parameter estimation of breast tumour using dynamic neural network from thermal pattern

    Directory of Open Access Journals (Sweden)

    Elham Saniei

    2016-11-01

    Full Text Available This article presents a new approach for estimating the depth, size, and metabolic heat generation rate of a tumour. For this purpose, the surface temperature distribution of a breast thermal image and the dynamic neural network was used. The research consisted of two steps: forward and inverse. For the forward section, a finite element model was created. The Pennes bio-heat equation was solved to find surface and depth temperature distributions. Data from the analysis, then, were used to train the dynamic neural network model (DNN. Results from the DNN training/testing confirmed those of the finite element model. For the inverse section, the trained neural network was applied to estimate the depth temperature distribution (tumour position from the surface temperature profile, extracted from the thermal image. Finally, tumour parameters were obtained from the depth temperature distribution. Experimental findings (20 patients were promising in terms of the model’s potential for retrieving tumour parameters.

  14. Translation elongation factor eEF1A2 is a potential oncoprotein that is overexpressed in two-thirds of breast tumours

    Directory of Open Access Journals (Sweden)

    Miller William R

    2005-09-01

    Full Text Available Abstract Background The tissue-specific translation elongation factor eEF1A2 was recently shown to be a potential oncogene that is overexpressed in ovarian cancer. Although there is no direct evidence for an involvement of eEF1A2 in breast cancer, the genomic region to which EEF1A2 maps, 20q13, is frequently amplified in breast tumours. We therefore sought to establish whether eEF1A2 expression might be upregulated in breast cancer. Methods eEF1A2 is highly similar (98% to the near-ubiquitously expressed eEF1A1 (formerly known as EF1-α making analysis with commercial antibodies difficult. We have developed specific anti-eEF1A2 antibodies and used them in immunohistochemical analyses of tumour samples. We report the novel finding that although eEF1A2 is barely detectable in normal breast it is moderately to strongly expressed in two-thirds of breast tumours. This overexpression is strongly associated with estrogen receptor positivity. Conclusion eEF1A2 should be considered as a putative oncogene in breast cancer that may be a useful diagnostic marker and therapeutic target for a high proportion of breast tumours. The oncogenicity of eEF1A2 may be related to its role in protein synthesis or to its potential non-canonical functions in cytoskeletal remodelling or apoptosis.

  15. Oestrogen and progesterone receptor assays in breast tumours. The Prince Henry's Hospital experience, 1983-1990.

    Science.gov (United States)

    Pearce, P T; Myles, K M; Funder, J W

    1993-08-16

    To present and analyse the results of eight years of experience (1983-1990) in breast tumour receptor analysis. All female primary breast tumour samples received (4683) were analysed for seasonal variation, patient age, relative risk index, oestrogen receptor (ER) and progesterone receptor (PR) status, ER and PR status as a function of age, ER and PR levels as a function of age, and ER and PR levels as a function of month of analysis. The assays were done at the Medical Research Centre, Prince Henry's Hospital, Melbourne, as a non-profit service to surgeons, oncologists and pathologists. The numbers of samples referred for assay increased progressively each year, from 473 in 1983 to 1097 in 1990, but the receptor status (ER +/-, PR +/-) appeared not to vary from year to year. ER+PR+ tumours were the most common in all age groups, steadily increasing from between 50% and 60% in premenopausal women to 70% or more in those aged over 80. In postmenopausal women, levels of ER in ER+ tumours were three times those in premenopausal women; PR levels in PR+ tumours, however, were bimodal, with higher levels in the age groups 35-49 and 70-89 years than in women aged 50-69 years. No significant seasonal variation was seen, and the overall patterns of receptor status are similar to those seen in Northern hemisphere studies.

  16. Assessment of DNA methylation profiling and copy number variation as indications of clonal relationship in ipsilateral and contralateral breast cancers to distinguish recurrent breast cancer from a second primary tumour

    International Nuclear Information System (INIS)

    Huang, Katie T.; Mikeska, Thomas; Li, Jason; Takano, Elena A.; Millar, Ewan K A; Graham, Peter H.; Boyle, Samantha E.; Campbell, Ian G.; Speed, Terence P.; Dobrovic, Alexander; Fox, Stephen B.

    2015-01-01

    Patients with breast cancer have an increased risk of developing subsequent breast cancers. It is important to distinguish whether these tumours are de novo or recurrences of the primary tumour in order to guide the appropriate therapy. Our aim was to investigate the use of DNA methylation profiling and array comparative genomic hybridization (aCGH) to determine whether the second tumour is clonally related to the first tumour. Methylation-sensitive high-resolution melting was used to screen promoter methylation in a panel of 13 genes reported as methylated in breast cancer (RASSF1A, TWIST1, APC, WIF1, MGMT, MAL, CDH13, RARβ, BRCA1, CDH1, CDKN2A, TP73, and GSTP1) in 29 tumour pairs (16 ipsilateral and 13 contralateral). Using the methylation profile of these genes, we employed a Bayesian and an empirical statistical approach to estimate clonal relationship. Copy number alterations were analysed using aCGH on the same set of tumour pairs. There is a higher probability of the second tumour being recurrent in ipsilateral tumours compared with contralateral tumours (38 % versus 8 %; p <0.05) based on the methylation profile. Using previously reported recurrence rates as Bayesian prior probabilities, we classified 69 % of ipsilateral and 15 % of contralateral tumours as recurrent. The inferred clonal relationship results of the tumour pairs were generally concordant between methylation profiling and aCGH. Our results show that DNA methylation profiling as well as aCGH have potential as diagnostic tools in improving the clinical decisions to differentiate recurrences from a second de novo tumour. The online version of this article (doi:10.1186/s12885-015-1676-0) contains supplementary material, which is available to authorized users

  17. Identifying Breast Cancer Oncogenes

    Science.gov (United States)

    2011-10-01

    cells we observed that it promoted transformation of HMLE cells, suggesting a tumor suppressive role of Merlin in breast cancer (Figure 4B). A...08-1-0767 TITLE: Identifying Breast Cancer Oncogenes PRINCIPAL INVESTIGATOR: Yashaswi Shrestha...Standard Form 298 (Rev. 8-98) Prescribed by ANSI Std. Z39.18 W81XWH-08-1-0767 Identifying Breast Cancer Oncogenes Yashaswi Shrestha Dana-Farber

  18. Expression profiling of nuclear receptors in breast cancer identifies TLX as a mediator of growth and invasion in triple-negative breast cancer.

    Science.gov (United States)

    Lin, Meng-Lay; Patel, Hetal; Remenyi, Judit; Banerji, Christopher R S; Lai, Chun-Fui; Periyasamy, Manikandan; Lombardo, Ylenia; Busonero, Claudia; Ottaviani, Silvia; Passey, Alun; Quinlan, Philip R; Purdie, Colin A; Jordan, Lee B; Thompson, Alastair M; Finn, Richard S; Rueda, Oscar M; Caldas, Carlos; Gil, Jesus; Coombes, R Charles; Fuller-Pace, Frances V; Teschendorff, Andrew E; Buluwela, Laki; Ali, Simak

    2015-08-28

    The Nuclear Receptor (NR) superfamily of transcription factors comprises 48 members, several of which have been implicated in breast cancer. Most important is estrogen receptor-α (ERα), which is a key therapeutic target. ERα action is facilitated by co-operativity with other NR and there is evidence that ERα function may be recapitulated by other NRs in ERα-negative breast cancer. In order to examine the inter-relationships between nuclear receptors, and to obtain evidence for previously unsuspected roles for any NRs, we undertook quantitative RT-PCR and bioinformatics analysis to examine their expression in breast cancer. While most NRs were expressed, bioinformatic analyses differentiated tumours into distinct prognostic groups that were validated by analyzing public microarray data sets. Although ERα and progesterone receptor were dominant in distinguishing prognostic groups, other NR strengthened these groups. Clustering analysis identified several family members with potential importance in breast cancer. Specifically, RORγ is identified as being co-expressed with ERα, whilst several NRs are preferentially expressed in ERα-negative disease, with TLX expression being prognostic in this subtype. Functional studies demonstrated the importance of TLX in regulating growth and invasion in ERα-negative breast cancer cells.

  19. Oestrogen receptors in breast tumours: associations with age, menopausal status and epidemiological and clinical features in 735 patients.

    Science.gov (United States)

    Elwood, J M; Godolphin, W

    1980-11-01

    Comparisons between oestrogen-receptor (RE)-positive or negative patients were made on a continuous series of 735 patients with primary breast tumours seen at the major treatment centre in British Columbia between 1975 and 1978. RE positivity was commoner in older patients, and was not associated with menopausal status independently of age. The concentration of receptor protein also increased with increasing age, but was not affected by menopausal status. Neither RE status nor quantity was associated with any of the epidemiological risk factors studied, which included parity, age at first birth, weight, family history and exposure to oestrogenic drugs and oral contraceptives. Patients with RE- tumours were more likely to present with symptoms other than a breast lump, pain or nipple inversion, and had less-differentiated tumours; they did not differ from RE+ patients in terms of stage, size of tumour, or interval from first symptom. These findings are discussed in terms of the biological origin and determinants of oestrogen receptors.

  20. Higher serum concentrations of vimentin and DAKP1 are associated with aggressive breast tumour phenotypes in Ghanaian women

    NARCIS (Netherlands)

    Arko-Boham, Benjamin; Lomotey, Justice Tanihu; Tetteh, Emmanuel Nomo; Tagoe, Emmanuel Ayitey; Aryee, Nii Ayite; Owusu, Ewurama Ampadu; Okai, Isaac; Blay, Richard Michael; Clegg-Lamptey, Joe-Nat

    2017-01-01

    Breast cancer, the most commonly diagnosed cancer among women and leading cause of cancer-related deaths worldwide, exhibits aggressive behavior in indigenous African women evidenced by high histologic grade tumours with low hormone receptor positivity. Aggressive breast cancers grow quickly, easily

  1. Correlation between the Histo-Pathological Grade and Tumour Uptake Analysis of Tc99m-MIBI in Breast Cancer Nodules

    International Nuclear Information System (INIS)

    Haider, Saima

    2006-01-01

    Full text: Breast Cancer is the most common malignancy among women in the world. X-Ray mammography is the best screening device, but radionuclide imaging such as Tc-99m MIBI Scintimammography promises to play an important role as an adjunctive functional imaging tool in breast malignancies. The aim of the study was to correlate the Histopathological grade and semi-quantitative analysis of tracer uptake in Tc-99m MIBI Scintimammography. Seven (7) female patients (mean age 47.5+10) with locally advanced breast cancer were imaged. Informed written consent was taken from each patient. Average of 950 MBq (0.3 mCi/kg) Tc-99m MIBI was injected intravenously in the contra lateral arm to the site of lesion. Static prone MIBI Scintimammoscans of the affected side was acquired 5-10 minutes post injection for 10 minutes. Similarly 10 minute static view of normal side was also done. The background subtracted lesions to normal ratios (LNR) were acquired. Histopathological grading of tumours was done according to Bloom Richardson grading system. All the tumours were infiltrating ductal carcinoma. The mean LNR value is higher in high-grade lesions while less in low-grade tumours. Higher un-differentiation of malignant tumour is related with aggressive nature of the disease. This would suggest that more aggressive tumours have higher uptake of Tc-99m MIBI and therefore greater invasiveness of malignancy. (author)

  2. Breast Carcinoma Progression and Tumour Vascular Markers Related to Apoptotic Mechanisms

    Directory of Open Access Journals (Sweden)

    Miroslava Bilecova-Rabajdova

    2014-01-01

    Full Text Available Background. In the last few years, the cancer research had tried to identify and characterize new biochemical and molecular pathways in which the inhibition induces prosurvival mechanisms. Our work describes the expression of two different members of apoptotic regulatory pathway and their relationship with a progression of breast carcinoma. Materials and Methods. We compared expression of genes related to apoptosis (DR6 and Gpm6B in the blood of patients suffering from stage I of breast cancer in different grades (I–IV, with healthy controls. After isolation of mRNA, transcription of mRNA into the cDNA was performed. The quantification of gene expression changes in DR6 and Gpm6B was detected by RT-PCR method. Analysis at the protein level was performed by the Western blot.Results. In statistical analysis of Dr6 mRNA level changes we detected significant increase starting in Grading 1 (G1 and reached maximal level in G3.This expression on mRNA levels was similar to protein levels, which copy rising tendency with maximal value in G3. The results of Gpm6B were significantly lower.Conclusion. This result showed that antiapoptotic signalling during neovascularization is increased significantly. It would be advisable in the future to study the influence of cytostatic treatment on the expression of genes related to apoptotic pathways and their relationship with progression of breast cancer tumours.

  3. Histopathology of tumour associated sarcoid-like stromal reaction in breast cancer. An analysis of 5 cases with immunohistochemical investigations.

    Science.gov (United States)

    Bässler, R; Birke, F

    1988-01-01

    In 5 cases of invasive ductal and lobular carcinoma of the breast multiple epithelioid and giant cell containing granulomas were detected, localized mainly in circumferential regions, but also in the center of the carcinomas. These granulomas were interpreted as sarcoid-like stromal reactions, occurring as sarcoid-like lesions in uni- and bilateral primaries, in a recurrent tumour, and also in axillary lymph nodes. Histopathologically, these granulomas were not quite uniform, some of them corresponding to typical sarcoidosis, others showing marked proliferations of epithelioid or giant cells or containing fibrinoid exudate or necroses. The granulomas were surrounded by dense infiltrates of mononuclear cells. Tuberculosis and mycosis was excluded. There were no hints of generalized sarcoidosis. Pathogenetically, these are reactions in the tumour stroma of varying intensity, and are not caused by necroses of the tumour tissue nor by microbial infections. Such tumour-associated sarcoid-like stroma reactions are interpreted as a T-cell mediated immune response to an antigen expression of the carcinoma acting as the local trigger; in 2 cases they were connected with sarcoid-like lesions of the axillary lymph nodes. Their occurrence in bilateral carcinoma of the breast points to an immunological disposition for this special kind of host-versus-tumour response. The intensity of these changes in a recurrent tumour reflects an immunological hypersensitivity reaction. The pathogenetic and differential diagnostic aspects of epithelioid granulomas of the female breast in chronic granulomatous mastitis, panniculitis, foreign body reaction, rare infections, and in therapeutically induced sarcoidosis are described and discussed.

  4. Breast Cancer with Synchronous Renal Cell Carcinoma: A Rare Presentation.

    Science.gov (United States)

    Arjunan, Ravi; Kumar, Durgesh; Kumar, K V Veerendra; Premlatha, C S

    2016-10-01

    Primary cancer arising from multiple organs is a well known fact. Synchronous tumours have been most commonly associated with kidney cancer. Bladder, prostate, colorectal and lung cancer are the most common synchronous primaries with Renal Cell Carcinoma (RCC) identified till date. We found metachronous tumours of breast with RCC in literature search which included both metastatic tumours as well second primaries. Overall, 25 cases of metastatic breast tumours and eight cases of second primary in previously treated RCC have been reported in the literature. Here, we are reporting a case of synchronous presentation of carcinoma breast with RCC which is very rare because most of the multiple malignancies reported in the literature are metastatic tumours or metachronous breast malignancy with RCC.

  5. Egfr Amplification Specific Gene Expression in Phyllodes Tumours of the Breast

    Directory of Open Access Journals (Sweden)

    Konstantin Agelopoulos

    2007-01-01

    Full Text Available Background: Recently, we were able to show that amplifications of the epidermal growth factor receptor (egfr gene and the overexpression of EGFR were associated with the initiation and progression of phyllodes tumours. Methods: In order to gain further insights into regulation mechanisms associated with egfr amplifications and EGFR expression in phyllodes tumours, we performed global gene expression analysis (Affymetrix A133.2 on a series of 10 phyllodes tumours, of these three with and seven without amplifications of an important regulatory repeat in intron 1 of egfr (CA-SSR I. The results were verified and extended by means of immunohistochemistry using the tissue microarray method on an extensively characterized series of 58 phyllodes tumours with antibodies against caveolin-1, eps15, EGF, TGF-α, pErk, pAkt and mdm2. Results: We were able to show that the presence of egfr CA-SSR I amplifications in phyllodes tumours was associated with 230 differentially expressed genes. Caveolin-1 and eps15, involved in EGFR turnover and signalling, were regulated differentially on the RNA and protein level proportionally to egfr gene dosage. Further immunohistochemical analysis revealed that the expression of caveolin-1 and eps15 were also significantly correlated with the expression of pAkt (p < 0.05, pERK (p < 0.05, mdm2 (p < 0.01 and EGF (p < 0.001 for caveolin-1. Eps15 and pERK were further associated with tumour grade (p < 0.01 and p < 0.001, respectively. Conclusion: Our results show that amplifications within regulatory sequences of egfr are associated with the expression of eps15 and caveolin-1, indicating an increased turnover of EGFR. The interplay between EGFR and caveolin-1, eps15, pAkt, mdm2 and pERK therefore seems to present a major molecular pathway in carcinogenesis and progression of breast phyllodes tumours.

  6. Is there a requirement for axillary lymph node dissection following identification of micro-metastasis or isolated tumour cells at sentinel node biopsy for breast cancer?

    LENUS (Irish Health Repository)

    Joyce, D P

    2012-02-29

    INTRODUCTION: Recent decades have seen a significant shift towards conservative management of the axilla. Increasingly, immunohistochemical analysis of sentinel nodes leads to the detection of small tumour deposits, the significance of which remains uncertain. The aims of this study are to examine patients whose sentinel lymph nodes are positive for macro-metastasis, micro-metastasis or isolated tumour cells (ITCs) and to determine the rate of further nodal disease after axillary lymph node dissection (ALND). METHODS: A retrospective analysis of all patients undergoing a sentinel lymph node biopsy (SLNB) between January 2007 and December 2010 in a tertiary referral breast unit was performed. Patients who underwent an axillary lymph node dissection for macro-metastasis, micro-metastasis or ITCs were identified. Demographics, histological data and the rate of further axillary disease were examined. RESULTS: In total, 664 breast cancer patients attended the symptomatic breast unit during the study period, 360 of whom underwent a SLNB. Seventy patients had a SLNB positive for macro-metastasis. All of these patients underwent ALND. A positive SLNB with either micro-metastasis or ITCs was identified in 58 patients. Only 41 of the 58 patients went on to have an ALND, due primarily to variations in surgeons\\' preferences. Nineteen patients with micro-metastasis underwent an ALND. Four patients had further axillary disease (21%). Twenty-two patients had ITCs identified, of whom only one had further disease (4.5%). No statistically significant difference was found between the two groups in terms of tumour size, grade, lymphovascular invasion or oestrogen receptor status. CONCLUSION: ALND should be considered in patients with micro-metastasis at SLNB. It should rarely be employed in the setting of SLNB positive for ITCs.

  7. A monograph proposing the use of canine mammary tumours as a model for the study of hereditary breast cancer susceptibility genes in humans.

    Science.gov (United States)

    Goebel, Katie; Merner, Nancy D

    2017-05-01

    Canines are excellent models for cancer studies due to their similar physiology and genomic sequence to humans, companion status and limited intra-breed heterogeneity. Due to their affliction to mammary cancers, canines can serve as powerful genetic models of hereditary breast cancers. Variants within known human breast cancer susceptibility genes only explain a fraction of familial cases. Thus, further discovery is necessary but such efforts have been thwarted by genetic heterogeneity. Reducing heterogeneity is key, and studying isolated human populations have helped in the endeavour. An alternative is to study dog pedigrees, since artificial selection has resulted in extreme homogeneity. Identifying the genetic predisposition to canine mammary tumours can translate to human discoveries - a strategy currently underutilized. To explore this potential, we reviewed published canine mammary tumour genetic studies and proposed benefits of next generation sequencing canine cohorts to facilitate moving beyond incremental advances.

  8. Two cases of breast carcinoma with osteoclastic giant cells: Are the osteoclastic giant cells pro-tumoural differentiation of macrophages?

    Directory of Open Access Journals (Sweden)

    Shishido-Hara Yukiko

    2010-08-01

    Full Text Available Abstract Breast carcinoma with osteoclastic giant cells (OGCs is characterized by multinucleated OGCs, and usually displays inflammatory hypervascular stroma. OGCs may derive from tumor-associated macrophages, but their nature remains controversial. We report two cases, in which OGCs appear in common microenvironment despite different tumoural histology. A 44-year-old woman (Case 1 had OGCs accompanying invasive ductal carcinoma, and an 83-year-old woman (Case 2 with carcinosarcoma. Immunohistochemically, in both cases, tumoural and non-tumoural cells strongly expressed VEGF and MMP12, which promote macrophage migration and angiogenesis. The Chalkley count on CD-31-stained sections revealed elevated angiogenesis in both cases. The OGCs expressed bone-osteoclast markers (MMP9, TRAP, cathepsin K and a histiocyte marker (CD68, but not an MHC class II antigen, HLA-DR. The results indicate a pathogenesis: regardless of tumoural histology, OGCs derive from macrophages, likely in response to hypervascular microenvironments with secretion of common cytokines. The OGCs have acquired bone-osteoclast-like characteristics, but lost antigen presentation abilities as an anti-cancer defense. Appearance of OGCs may not be anti-tumoural immunological reactions, but rather pro-tumoural differentiation of macrophage responding to hypervascular microenvironments induced by breast cancer.

  9. An imbalance in progenitor cell populations reflects tumour progression in breast cancer primary culture models.

    LENUS (Irish Health Repository)

    Donatello, Simona

    2011-01-01

    Many factors influence breast cancer progression, including the ability of progenitor cells to sustain or increase net tumour cell numbers. Our aim was to define whether alterations in putative progenitor populations could predict clinicopathological factors of prognostic importance for cancer progression.

  10. High-intensity focused ultrasound in the treatment of breast tumours.

    Science.gov (United States)

    Peek, Mirjam C L; Wu, Feng

    2018-01-01

    High-intensity focused ultrasound (HIFU) is a minimally invasive technique that has been used for the treatment of both benign and malignant tumours. With HIFU, an ultrasound (US) beam propagates through soft tissue as a high-frequency pressure wave. The US beam is focused at a small target volume, and due to the energy building up at this site, the temperature rises, causing coagulative necrosis and protein denaturation within a few seconds. HIFU is capable of providing a completely non-invasive treatment without causing damage to the directly adjacent tissues. HIFU can be either guided by US or magnetic resonance imaging (MRI). Guided imaging is used to plan the treatment, detect any movement during the treatment and monitor response in real-time. This review describes the history of HIFU, the HIFU technique, available devices and gives an overview of the published literature in the treatment of benign and malignant breast tumours with HIFU.

  11. Which techniques for an additional irradiation of the tumour bed in a breast cancer?

    International Nuclear Information System (INIS)

    Chenna, H.; Iraqi, M.; Ahmedou, M.M.; Berhil, H.; El Kacemi, H.; Hassouni, K.; Kebdani, T.; Benjaafar, N.; El Gueddari, B.K.

    2010-01-01

    The authors report a comparison of different techniques for an additional irradiation of the tumour bed, in terms of local control and aesthetic result in the case of a breast cancer. This additional irradiation has been delivered by electron beam in five fractions, high dose rate curie-therapy in two fractions, photon beam in five or six fractions, and low dose rate curie-therapy. The dose increase in the tumour bed allows the local control rate to be increased without compromising aesthetic results. However, the comparison of the different boost techniques does not reveal significant differences. Short communication

  12. Mechanisms driving local breast cancer recurrence in a model of breast-conserving surgery.

    LENUS (Irish Health Repository)

    Smith, Myles J

    2012-02-03

    OBJECTIVE: We aimed to identify mechanisms driving local recurrence in a model of breast-conserving surgery (BCS) for breast cancer. BACKGROUND: Breast cancer recurrence after BCS remains a clinically significant, but poorly understood problem. We have previously reported that recurrent colorectal tumours demonstrate altered growth dynamics, increased metastatic burden and resistance to apoptosis, mediated by upregulation of phosphoinositide-3-kinase\\/Akt (PI3K\\/Akt). We investigated whether similar characteristics were evident in a model of locally recurrent breast cancer. METHODS: Tumours were generated by orthotopic inoculation of 4T1 cells in two groups of female Balb\\/c mice and cytoreductive surgery performed when mean tumour size was above 150 mm(3). Local recurrence was observed and gene expression was examined using Affymetrix GeneChips in primary and recurrent tumours. Differential expression was confirmed with quantitative real-time polymerase chain reaction (qRT-PCR). Phosphorylation of Akt was assessed using Western immunoblotting. An ex vivo heat shock protein (HSP)-loaded dendritic cell vaccine was administered in the perioperative period. RESULTS: We observed a significant difference in the recurrent 4T1 tumour volume and growth rate (p < 0.05). Gene expression studies suggested roles for the PI3K\\/Akt system and local immunosuppression driving the altered growth kinetics. We demonstrated that perioperative vaccination with an ex vivo HSP-loaded dendritic cell vaccine abrogated recurrent tumour growth in vivo (p = 0.003 at day 15). CONCLUSION: Investigating therapies which target tumour survival pathways such as PI3K\\/Akt and boost immune surveillance in the perioperative period may be useful adjuncts to contemporary breast cancer treatment.

  13. Inflammatory breast cancer biology: the tumour microenvironment is key.

    Science.gov (United States)

    Lim, Bora; Woodward, Wendy A; Wang, Xiaoping; Reuben, James M; Ueno, Naoto T

    2018-04-27

    Inflammatory breast cancer (IBC) is a rare and aggressive disease that accounts for ~2-4% of all breast cancers. However, despite its low incidence rate, IBC is responsible for 7-10% of breast cancer-related mortality in Western countries. Thus, the discovery of robust biological targets and the development of more effective therapeutics in IBC are crucial. Despite major international efforts to understand IBC biology, genomic studies have not led to the discovery of distinct biological mechanisms in IBC that can be translated into novel therapeutic strategies. In this Review, we discuss these molecular profiling efforts and highlight other important aspects of IBC biology. We present the intrinsic characteristics of IBC, including stemness, metastatic potential and hormone receptor positivity; the extrinsic features of the IBC tumour microenvironment (TME), including various constituent cell types; and lastly, the communication between these intrinsic and extrinsic components. We summarize the latest perspectives on the key biological features of IBC, with particular emphasis on the TME as an important contributor to the aggressive nature of IBC. On the basis of the current understanding of IBC, we hope to develop the next generation of translational studies, which will lead to much-needed survival improvements in patients with this deadly disease.

  14. A simple method for assigning genomic grade to individual breast tumours

    International Nuclear Information System (INIS)

    Wennmalm, Kristian; Bergh, Jonas

    2011-01-01

    The prognostic value of grading in breast cancer can be increased with microarray technology, but proposed strategies are disadvantaged by the use of specific training data or parallel microscopic grading. Here, we investigate the performance of a method that uses no information outside the breast profile of interest. In 251 profiled tumours we optimised a method that achieves grading by comparing rank means for genes predictive of high and low grade biology; a simpler method that allows for truly independent estimation of accuracy. Validation was carried out in 594 patients derived from several independent data sets. We found that accuracy was good: for low grade (G1) tumors 83- 94%, for high grade (G3) tumors 74- 100%. In keeping with aim of improved grading, two groups of intermediate grade (G2) cancers with significantly different outcome could be discriminated. This validates the concept of microarray-based grading in breast cancer, and provides a more practical method to achieve it. A simple R script for grading is available in an additional file. Clinical implementation could achieve better estimation of recurrence risk for 40 to 50% of breast cancer patients

  15. A simple method for assigning genomic grade to individual breast tumours

    Directory of Open Access Journals (Sweden)

    Bergh Jonas

    2011-07-01

    Full Text Available Abstract Background The prognostic value of grading in breast cancer can be increased with microarray technology, but proposed strategies are disadvantaged by the use of specific training data or parallel microscopic grading. Here, we investigate the performance of a method that uses no information outside the breast profile of interest. Results In 251 profiled tumours we optimised a method that achieves grading by comparing rank means for genes predictive of high and low grade biology; a simpler method that allows for truly independent estimation of accuracy. Validation was carried out in 594 patients derived from several independent data sets. We found that accuracy was good: for low grade (G1 tumors 83- 94%, for high grade (G3 tumors 74- 100%. In keeping with aim of improved grading, two groups of intermediate grade (G2 cancers with significantly different outcome could be discriminated. Conclusion This validates the concept of microarray-based grading in breast cancer, and provides a more practical method to achieve it. A simple R script for grading is available in an additional file. Clinical implementation could achieve better estimation of recurrence risk for 40 to 50% of breast cancer patients.

  16. Progression of fibroadenoma to malignant phyllodes tumour in a 14-year female

    International Nuclear Information System (INIS)

    Faridi, S.H.; Aslam, M.; Siddiqui, B.; Ahmad, S.S.

    2018-01-01

    Phyllodes tumours are uncommon breast tumours which account for less than 1% of all breast neoplasms. High-grade malignant phyllodes tumour is a very rare but aggressive breast malignancy and forms approximately 15-30% of all phyllodes tumours. The transformation of a benign fibroadenoma into a malignant phyllodes tumour in a teenaged female is even rarer. We report here an interesting case of malignant phyllodes tumour in a 14-year female patient who was operated twice previously with the diagnosis of complex fibroadenoma in the same breast. There was a large tumour involving whole of the breast and infiltrating the skin. The patient was operated and total mastectomy was done. Diagnosis was confirmed after histopathological examination and immunohistochemistry of the resected specimen. Patient received adjuvant radiotherapy and there was no recurrence on 6-month follow-up. Owing to the rare occurrence of malignant phyllodes tumour in this age group along with previous operations for complex fibroadenoma, this case is being reported here. (author)

  17. Tumour characteristics and survival in patients with invasive interval breast cancer classified according to mammographic findings at the latest screening

    DEFF Research Database (Denmark)

    Vitak, B; Olsen, K E; Månson, J C

    1999-01-01

    with invasive interval cancer detected from May 1978 to August 1995 (n = 544). The tumours were evaluated with regard to age, radiological category, interval between the latest screen and diagnosis and tumour characteristics at the time of diagnosis. We investigated possible relationships between the survival...... screen and diagnosis were not genuine predictors of the prognosis in patients with invasive interval breast cancer. No certain prognostic difference existed between true interval cancers and overlooked or misinterpreted interval breast cancers, despite higher proportions of grade-I tumours, ER positive......The aim of this study was to investigate whether different mammographic categories of interval cancer classified according to findings at the latest screening are associated with different distributions of prognostic factors or with different survival rates. The series consisted of all patients...

  18. Screening of 1331 Danish breast and/or ovarian cancer families identified 40 novel BRCA1 and BRCA2 mutations

    DEFF Research Database (Denmark)

    Hansen, Thomas V O; Jønson, Lars; Steffensen, Ane Y

    2011-01-01

    Germ-line mutations in the tumour suppressor genes BRCA1 and BRCA2 predispose to breast and ovarian cancer. Since 1999 we have performed mutational screening of breast and/or ovarian cancer patients in East Denmark. During this period we have identified 40 novel sequence variations in BRCA1...... and BRCA2 in high risk breast and/or ovarian cancer families. The mutations were detected via pre-screening using dHPLC or high-resolution melting and direct sequencing. We identified 16 variants in BRCA1, including 9 deleterious frame-shift mutations, 2 intronic variants, 4 missense mutations, and 1......, the presumed significance of the missense mutations was predicted in silico using the align GVGD algorithm. In conclusion, the mutation screening identified 40 novel variants in the BRCA1 and BRCA2 genes and thereby extends the knowledge of the BRCA1/BRCA2 mutation spectrum. Nineteen of the mutations were...

  19. A comparison of tumour size measurements with palpation, ultrasound and mammography in male breast cancer: first results of the prospective register study.

    Science.gov (United States)

    Streng, Martin; Ignatov, Atanas; Reinisch, Mattea; Costa, Serban-Dan; Eggemann, Holm

    2018-02-01

    Precise presurgical diagnosis of tumour size is essential for adequate treatment of male breast cancer (MBC). This study is aimed to compare the accuracy of clinical measurement (CE), ultrasound (US) and mammography (MG) for preoperative estimation of tumour size. This study was conducted as a prospective, multicentre register study. One hundred and twenty-nine male patients with invasive breast cancer were included. CE, US and MG were performed in 107, 110 and 75 patients, respectively, and the estimated tumour size was compared with the histopathological (HP) tumour size. All methods tended to underestimate the HP tumour size. None of the methods were significantly more accurate than the others in determining the maximal tumour diameter. The sensitivity within 5 mm tolerance for US was 65.5%, which was better than for MG (61.3%) and CE (56.6%). In the group of patients with pT2 tumours, MG showed significantly better accuracy than US. The measurements obtained with each method were significantly correlated with the HP measurements. The highest correlation coefficient was observed for MG (0.788), followed by US (0.741) and CE (0.671). Our data demonstrate that MG and US have similar accuracy with regard to tumour size estimation. US assessment showed the highest sensitivity in determining tumour size, followed by MG and CE. However, MG demonstrated a significant advantage for estimating the real tumour size for pT2 tumours compared to US or CE.

  20. Tumour and lymph node uptakes on dual-phased 2-deoxy-2-[18F]fluoro-D-glucose positron emission tomography/computed tomography correlate with prognostic parameters in breast cancer.

    Science.gov (United States)

    Chang, Chin-Chuan; Tu, Hung-Pin; Chen, Yu-Wen; Lin, Chia-Yang; Hou, Ming-Feng

    2014-12-01

    To examine correlations between the uptake of 2-deoxy-2-[18F]fluoro-D-glucose (FDG) by primary tumours and axillary lymph nodes, and clinical and biological tumour prognostic parameters, in patients with newly diagnosed breast cancer. Newly diagnosed breast cancer patients who had received a dual-phased FDG positron emission tomography/computed tomography scan for pretreatment staging were enrolled retrospectively. Maximal standardized uptake values at 1 h (SUV1), 2 h (SUV2), and retention indices (RI) of the tumours and ipsilateral axillary lymph nodes were measured. SUV and RI were compared with clinical and biological prognostic parameters. A total of 32 patients participated in the study. Tumour FDG uptake correlated with histological grade and tumour size. FDG uptake in axillary lymph nodes correlated positively with lymph node status, metastasis status and clinical stage. RI values for the tumour and lymph nodes were significantly positively correlated with human epidermal growth factor receptor-2 positivity. FDG uptake in tumours and lymph nodes showed correlations with some clinical and biological parameters, and may serve as a predictive marker of tumour biological behaviour in breast cancer. © The Author(s) 2014 Reprints and permissions: sagepub.co.uk/journalsPermissions.nav.

  1. Improved contrast deep optoacoustic imaging using displacement-compensated averaging: breast tumour phantom studies

    Energy Technology Data Exchange (ETDEWEB)

    Jaeger, M; Preisser, S; Kitz, M; Frenz, M [Institute of Applied Physics, University of Bern, Sidlerstrasse 5, CH-3012 Bern (Switzerland); Ferrara, D; Senegas, S; Schweizer, D, E-mail: frenz@iap.unibe.ch [Fukuda Denshi Switzerland AG, Reinacherstrasse 131, CH-4002 Basel (Switzerland)

    2011-09-21

    For real-time optoacoustic (OA) imaging of the human body, a linear array transducer and reflection mode optical irradiation is usually preferred. Such a setup, however, results in significant image background, which prevents imaging structures at the ultimate depth determined by the light distribution and the signal noise level. Therefore, we previously proposed a method for image background reduction, based on displacement-compensated averaging (DCA) of image series obtained when the tissue sample under investigation is gradually deformed. OA signals and background signals are differently affected by the deformation and can thus be distinguished. The proposed method is now experimentally applied to image artificial tumours embedded inside breast phantoms. OA images are acquired alternately with pulse-echo images using a combined OA/echo-ultrasound device. Tissue deformation is accessed via speckle tracking in pulse echo images, and used to compensate in the OA images for the local tissue displacement. In that way, OA sources are highly correlated between subsequent images, while background is decorrelated and can therefore be reduced by averaging. We show that image contrast in breast phantoms is strongly improved and detectability of embedded tumours significantly increased, using the DCA method.

  2. A comparative study of tissue inhibitor of metalloproteinases-1 levels in plasma and tumour tissue from patients with primary breast cancer and in plasma from patients with metastatic breast cancer

    DEFF Research Database (Denmark)

    Rasmussen, Anne-Sofie Schrohl; Mueller, Volkmar; Christensen, Ib Jarle

    2008-01-01

    OBJECTIVE: Tissue inhibitor of metalloproteinases-1 (TIMP-1) has been investigated as a potential tumour marker in breast cancer. Here we investigated the correlation between TIMP-1 in tumour tissue and plasma to evaluate whether TIMP-1 in plasma is actually a surrogate marker for TIMP-1 in prima...

  3. MR imaging of the skin and nipple of the breast: differentiation between tumour recurrence and post-treatment change

    International Nuclear Information System (INIS)

    Ralleigh, G.; Walker, A.E.; Hall-Craggs, M.A.; Lakhani, S.R.; Saunders, C.

    2001-01-01

    Contrast-enhanced MR imaging of the breast has been found to be valuable in the assessment of local recurrence of previously treated breast cancer. We looked specifically at the appearances of the skin and nipple of the treated breast in order to describe the appearances of post-treatment change and recurrence in this region. Thirty-nine women treated for breast cancer had MR imaging of one or both breasts reviewed retrospectively with particular attention to the nipple and skin. The skin and chest wall were assessed for patients with mastectomies. All available histology of the skin and/or nipple, obtained following MR imaging, was reviewed. In patients who did not undergo surgery following MR imaging, clinical follow-up was obtained. Six of 39 cases had nodular enhancing areas seen on MR imaging, which correlated with histology demonstrating tumour recurrence within the skin and/or nipple. Of the remaining 33 patients, changes of linear or diffuse enhancement were seen in the skin and/or nipple of 15 patients. These changes were shown to be benign post-treatment changes at surgery/biopsy in 4 cases or by clinical follow-up in the remainder. In this article we demonstrate differing patterns of contrast enhancement within the skin and nipple in recurrent breast carcinoma vs post-treatment changes. This suggests that contrast-enhanced MR imaging of the breast may be a useful tool in differentiating tumour recurrence from post-treatment changes within the skin and nipple. (orig.)

  4. Glycosyltransferases as marker genes for the quantitative polymerase chain reaction-based detection of circulating tumour cells from blood samples of patients with breast cancer undergoing adjuvant therapy.

    Science.gov (United States)

    Kölbl, Alexandra C; Hiller, Roman A; Ilmer, Mathias; Liesche, Friederike; Heublein, Sabine; Schröder, Lennard; Hutter, Stefan; Friese, Klaus; Jeschke, Udo; Andergassen, Ulrich

    2015-08-01

    Altered glycosylation is a predominant feature of tumour cells; it serves for cell adhesion and detachment, respectively, and facilitates the immune escape of these cells. Therefore changes in the expression of glycosyltransferase genes could help to identify circulating tumour cells (CTCs) in the blood samples of cancer patients using a quantitative polymerase chain reaction (PCR) approach. Blood samples of healthy donors were inoculated with certain numbers of established breast cancer cell line cells, thus creating a model system. These samples were analysed by quantitative PCR for the expression of six different glycosyltransferase genes. The three genes with the best results in the model system were consecutively applied to samples from adjuvant breast cancer patients and of healthy donors. FUT3 and GALNT6 showed the highest increase in relative expression, while GALNT6 and ST3GAL3 were the first to reach statistically significant different ∆CT-values comparing the sample with and without addition of tumour cells. These three genes were applied to patient samples, but did not show any significant results that may suggest the presence of CTCs in the blood. Although the relative expression of some of the glycosyltransferase genes exhibited reasonable results in the model system, their application to breast cancer patient samples will have to be further improved, e.g. by co-analysis of patient blood samples by gold-standard methods.

  5. Tumour 18 F-FDG Uptake on preoperative PET/CT may predict axillary lymph node metastasis in ER-positive/HER2-negative and HER2-positive breast cancer subtypes

    Energy Technology Data Exchange (ETDEWEB)

    Kim, Jin You; Lee, Suck Hong; Kim, Suk [Pusan National University Hospital, Pusan National University School of Medicine and Medical Research Institute, Department of Radiology, Seo-gu, Busan (Korea, Republic of); Kang, Taewoo [Pusan National University Hospital, Busan Cancer Center, Busan (Korea, Republic of); Bae, Young Tae [Pusan National University Hospital, Department of Surgery, Busan (Korea, Republic of)

    2015-04-01

    To evaluate the association between tumour FDG uptake on preoperative PET/CT and axillary lymph node metastasis (ALNM) according to breast cancer subtype. The records of 671 patients with invasive breast cancer who underwent {sup 18} F-FDG PET/CT and surgery were reviewed. Using immunohistochemistry, tumours were divided into three subtypes: oestrogen receptor (ER)-positive/human epidermal growth factor receptor 2 (HER2)-negative, HER2-positive, and triple-negative. Tumour FDG uptake, expressed as maximum standardized uptake value (SUV{sub max}), and clinicopathological variables were analysed. ALNM was present in 187 of 461 ER-positive/HER2-negative, 54 of 97 HER2-positive, and 38 of 113 triple-negative tumours. On multivariate analysis, high tumour SUV{sub max} (≥4.25) (P < 0.001), large tumour size (>2 cm) (P = 0.003) and presence of lymphovascular invasion (P < 0.001) were independent variables associated with ALNM. On subset analyses, tumour SUV{sub max} maintained independent significance for predicting ALNM in ER-positive/HER2-negative (adjusted odds ratio: 3.277, P < 0.001) and HER2-positive tumours (adjusted odds ratio: 14.637, P = 0.004). No association was found for triple-negative tumours (P = 0.161). Tumour SUV{sub max} may be an independent prognostic factor for ALNM in patients with invasive breast cancer, especially in ER-positive/HER2-negative and HER2-positive subtypes, but not in those with triple-negative subtype. (orig.)

  6. Can tumour marker assays be a guide in the prescription of bone scan for breast and lung cancers?

    Energy Technology Data Exchange (ETDEWEB)

    Buffaz, P.-D.; Gauchez, A.S.; Caravel, J.P.; Vuillez, J.P.; Cura, C.; Agnius-Delord, C.; Fagret, D. [Service de Medecine Nucleaire, Centre Hospitalier Universitaire de Grenoble (France)

    1999-01-01

    Considering the current need to improve cost-effectiveness in cancer patient management, a prospective study was undertaken in order to define the optimal combination of bone scan and tumour marker assays in breast and lung cancer strategies, as has been done in the case of prostate cancer. All patients with breast or lung cancer referred to the Nuclear Medicine Department of the Grenoble Teaching Hospital between December 1995 and April 1997 were included. A blood sample was drawn in each case for marker assay (CA15-3 or CEA and CYFRA 21-1) on the same day as the bone scan. Two hundred and seventy-five patients were included: 118 with lung cancer and 157 with breast cancer. With regard to lung cancer, no information useful for guiding bone scan prescription was obtained through CEA and CYFRA 21-1 assays. For breast cancer, the results suggest that in asymptomatic patients, a CA15-3 level of less than 25 U/ml (upper normal value chosen as the threshold) is strongly predictive of a negative bone scan; by contrast, high tumour marker levels are predictive of neoplastic bone involvement. When a doubtful bone scan is obtained in a patient with breast cancer, a normal marker level makes it highly probable that bone scan abnormalities are not related to malignancy. (orig.) With 3 figs., 21 refs.

  7. Epigenetic reprogramming of breast cancer cells with oocyte extracts

    Directory of Open Access Journals (Sweden)

    Kumari Rajendra

    2011-01-01

    Full Text Available Abstract Background Breast cancer is a disease characterised by both genetic and epigenetic alterations. Epigenetic silencing of tumour suppressor genes is an early event in breast carcinogenesis and reversion of gene silencing by epigenetic reprogramming can provide clues to the mechanisms responsible for tumour initiation and progression. In this study we apply the reprogramming capacity of oocytes to cancer cells in order to study breast oncogenesis. Results We show that breast cancer cells can be directly reprogrammed by amphibian oocyte extracts. The reprogramming effect, after six hours of treatment, in the absence of DNA replication, includes DNA demethylation and removal of repressive histone marks at the promoters of tumour suppressor genes; also, expression of the silenced genes is re-activated in response to treatment. This activity is specific to oocytes as it is not elicited by extracts from ovulated eggs, and is present at very limited levels in extracts from mouse embryonic stem cells. Epigenetic reprogramming in oocyte extracts results in reduction of cancer cell growth under anchorage independent conditions and a reduction in tumour growth in mouse xenografts. Conclusions This study presents a new method to investigate tumour reversion by epigenetic reprogramming. After testing extracts from different sources, we found that axolotl oocyte extracts possess superior reprogramming ability, which reverses epigenetic silencing of tumour suppressor genes and tumorigenicity of breast cancer cells in a mouse xenograft model. Therefore this system can be extremely valuable for dissecting the mechanisms involved in tumour suppressor gene silencing and identifying molecular activities capable of arresting tumour growth. These applications can ultimately shed light on the contribution of epigenetic alterations in breast cancer and advance the development of epigenetic therapies.

  8. MRI fused with prone FDG PET/CT improves the primary tumour staging of patients with breast cancer

    Energy Technology Data Exchange (ETDEWEB)

    Garcia-Velloso, Maria J.; Ribelles, Maria J.; Rodriguez, Macarena; Sancho, Lidia; Prieto, Elena [Clinica Universidad de Navarra, Department of Nuclear Medicine, Pamplona (Spain); Fernandez-Montero, Alejandro [Clinica Universidad de Navarra, Department of Occupational Medicine, Pamplona (Spain); Santisteban, Marta [Clinica Universidad de Navarra, Department of Oncology, Pamplona (Spain); Rodriguez-Spiteri, Natalia; Martinez-Regueira, Fernando [Clinica Universidad de Navarra, Department of Surgery, Pamplona (Spain); Idoate, Miguel A. [Clinica Universidad de Navarra, Department of Pathology, Pamplona (Spain); Elizalde, Arlette; Pina, Luis J. [Clinica Universidad de Navarra, Department of Radiology, Pamplona (Spain)

    2017-08-15

    Our aim was to evaluate the diagnostic accuracy of magnetic resonance imaging (MRI) fused with prone 2-[fluorine-18]-fluoro-2-deoxy-D-glucose (FDG) positron emission tomography (PET) in primary tumour staging of patients with breast cancer. This retrospective study evaluated 45 women with 49 pathologically proven breast carcinomas. MRI and prone PET-CT scans with time-of-flight and point-spread-function reconstruction were performed with the same dedicated breast coil. The studies were assessed by a radiologist and a nuclear medicine physician, and evaluation of fused images was made by consensus. The final diagnosis was based on pathology (90 lesions) or follow-up ≥ 24 months (17 lesions). The study assessed 72 malignant and 35 benign lesions with a median size of 1.8 cm (range 0.3-8.4 cm): 31 focal, nine multifocal and nine multicentric cases. In lesion-by-lesion analysis, sensitivity, specificity, positive and negative predictive values were 97%, 80%, 91% and 93% for MRI, 96%, 71%, 87%, and 89% for prone PET, and 97%. 94%, 97% and 94% for MRI fused with PET. Areas under the curve (AUC) were 0.953, 0.850, and 0.983, respectively (p < 0.01). MRI fused with FDG-PET is more accurate than FDG-PET in primary tumour staging of breast cancer patients and increases the specificity of MRI. (orig.)

  9. Neglected giant fibroadenoma of the breast presenting like a fungating breast cancer in a premenarchal Nigerian teenager.

    Science.gov (United States)

    Arowolo, O A; Akinkuolie, A A; Adisa, A O; Obonna, G C; Olasode, B J

    2012-01-01

    Giant fibroadenoma of the breast is a type of rare benign breast tumour which can grow to a giant size, It is even rarer for this benign tumour to grow rapidly, ulcerate spontaneously and present like a fungating breast tumour in a way mimicking breast cancer. Carcinoma of the breast on the other hand has been on the increase so much that it has assumed an epidemiological dimension. In developing country such as Nigeria late presentation of breast cancer has remained a rule rather than exception and it is very common for patient to present with fungating breast lesion. This is a case presentation of a 14 year old premenarchal girl presenting with a massive ulcerating and fungating left breast mass that was initially thought to be a fungating locally advanced breast carcinoma on clinical examination. Further examination of the morphology of the resected surgical specimen and histological examination confirmed it to be giant fibroadenoma of the breast. The giant fungating breast tumour successfully managed by partial mastectomy and breast reconstruction with an excellent result and a high degree of patient satisfaction was achieved. Though a rare clinical entity benign breast tumour can present like a fungating breast cancer and this must be bore in mind especially in young adolescent patients presenting with ulcerating breast tumour.

  10. Joint modelling of longitudinal CEA tumour marker progression and survival data on breast cancer

    Science.gov (United States)

    Borges, Ana; Sousa, Inês; Castro, Luis

    2017-06-01

    This work proposes the use of Biostatistics methods to study breast cancer in patients of Braga's Hospital Senology Unit, located in Portugal. The primary motivation is to contribute to the understanding of the progression of breast cancer, within the Portuguese population, using a more complex statistical model assumptions than the traditional analysis that take into account a possible existence of a serial correlation structure within a same subject observations. We aim to infer which risk factors aect the survival of Braga's Hospital patients, diagnosed with breast tumour. Whilst analysing risk factors that aect a tumour markers used on the surveillance of disease progression the Carcinoembryonic antigen (CEA). As survival and longitudinal processes may be associated, it is important to model these two processes together. Hence, a joint modelling of these two processes to infer on the association of these was conducted. A data set of 540 patients, along with 50 variables, was collected from medical records of the Hospital. A joint model approach was used to analyse these data. Two dierent joint models were applied to the same data set, with dierent parameterizations which give dierent interpretations to model parameters. These were used by convenience as the ones implemented in R software. Results from the two models were compared. Results from joint models, showed that the longitudinal CEA values were signicantly associated with the survival probability of these patients. A comparison between parameter estimates obtained in this analysis and previous independent survival[4] and longitudinal analysis[5][6], lead us to conclude that independent analysis brings up bias parameter estimates. Hence, an assumption of association between the two processes in a joint model of breast cancer data is necessary. Results indicate that the longitudinal progression of CEA is signicantly associated with the probability of survival of these patients. Hence, an assumption of

  11. Analysis of the effects of exposure to acute hypoxia on oxidative lesions and tumour progression in a transgenic mouse breast cancer model

    Directory of Open Access Journals (Sweden)

    Lunt Sarah

    2008-05-01

    Full Text Available Abstract Background Tumour hypoxia is known to be a poor prognostic indicator, predictive of increased risk of metastatic disease and reduced survival. Genomic instability has been proposed as one of the potential mechanisms for hypoxic tumour progression. Both of these features are commonly found in many cancer types, but their relationship and association with tumour progression has not been examined in the same model. Methods To address this issue, we determined the effects of 6 week in vivo acute hypoxic exposure on the levels of mutagenic lipid peroxidation product, malondialdehyde, and 8-oxo-7,8-dihydro-2'-deoxyguanosine DNA (8-oxo-dG lesions in the transgenic polyomavirus middle T (PyMT breast cancer mouse model. Results We observed significantly increased plasma lipid peroxidation and 8-oxo-dG lesion levels in the hypoxia-exposed mice. Consumption of malondialdehyde also induced a significant increase in the PyMT tumour DNA lesion levels, however, these increases did not translate into enhanced tumour progression. We further showed that the in vivo exposure to acute hypoxia induced accumulation of F4/80 positive tumour-associated macrophages (TAMs, demonstrating a relationship between hypoxia and macrophages in an experimental model. Conclusion These data suggest that although exposure to acute hypoxia causes an increase in 8-oxo-dG lesions and TAMs in the PyMT tumours, these increases do not translate into significant changes in tumour progression at the primary or metastatic levels in this strong viral oncogene-driven breast cancer model.

  12. Lymphoscintigraphy and SPECT/CT in multicentric and multifocal breast cancer: does each tumour have a separate drainage pattern? Results of a Dutch multicentre study (MULTISENT)

    NARCIS (Netherlands)

    Brouwer, O. R.; Vermeeren, L.; van der Ploeg, I. M. C.; Valdés Olmos, R. A.; Loo, C. E.; Pereira-Bouda, L. M.; Smit, F.; Neijenhuis, P.; Vrouenraets, B. C.; Sivro-Prndelj, F.; Jap-A-Joe, S. M.; Borgstein, P. J.; Rutgers, E. J. Th; Oldenburg, H. S. A.

    2012-01-01

    To investigate whether lymphoscintigraphy and SPECT/CT after intralesional injection of radiopharmaceutical into each tumour separately in patients with multiple malignancies in one breast yields additional sentinel nodes compared to intralesional injection of the largest tumour only. Patients were

  13. Size, node status and grade of breast tumours: association with mammographic parenchymal patterns

    Energy Technology Data Exchange (ETDEWEB)

    Sala, E.; Solomon, L.; McCann, J. [Department of Community Medicine, Strangeways Research Laboratory, Worts Causeway, Cambridge (United Kingdom); Warren, R. [Cambridge and Huntingdon Breast Screening Service, Rosie Maternity Hospital, Robinson Way, Cambridge (United Kingdom); Duffy, S. [MRC-Biostatistics Unit, Institute of Public Health, Cambridge (United Kingdom); Luben, R. [Department of Clinical Gerontology, Strangeways Research Laboratory, Cambridge (United Kingdom); Day, N. [Department of Community Medicine, Institute of Public Health, Robinson Way, Cambridge, CB2 2SR (United Kingdom)

    2000-01-01

    A case-control study was designed to assess the association of mammographic parenchymal patterns with the risk of in-situ and invasive breast cancer. In addition, the relationship between tumour characteristics and mammographic patterns were also investigated. A total of 875 patients with breast cancer were selected and matched with 2601 controls. Mammographic parenchymal patterns of breast tissue were assessed according to Wolfe's classification, and statistical analysis was by conditional logistic regression. Relative to the N1 pattern, the odds ratios of having an invasive breast cancer associated with the P2 and DY patterns were 1.8 and 1.4, respectively. In addition, the odd ratios of having an invasive grade 3 breast cancer associated with the P2 and DY patterns were 2.8 and 3.9, respectively. Relative to the combined N1/P1 pattern, the odd ratios of having a breast cancer smaller than 14 mm, 15-29 mm, or larger than 30 mm associated with the combined high-risk P2/DY pattern (P2 + DY) were 1.2, 1.6, and 2.0, respectively. Finally, women with the P2/DY pattern were twice as likely to have a breast cancer which had already spread to the axillary nodes, compared to women with women with the N1/P1 pattern (odds ratios of 2.1 and 1.4, respectively). Our results confirm previous findings suggesting that mammographic parenchymal patterns may serve as indicators of risk for breast cancer. Our results also suggest that mammographic parenchymal patterns are associated with the stage at which breast cancer is detected. (orig.)

  14. Size, node status and grade of breast tumours: association with mammographic parenchymal patterns

    International Nuclear Information System (INIS)

    Sala, E.; Solomon, L.; McCann, J.; Warren, R.; Duffy, S.; Luben, R.; Day, N.

    2000-01-01

    A case-control study was designed to assess the association of mammographic parenchymal patterns with the risk of in-situ and invasive breast cancer. In addition, the relationship between tumour characteristics and mammographic patterns were also investigated. A total of 875 patients with breast cancer were selected and matched with 2601 controls. Mammographic parenchymal patterns of breast tissue were assessed according to Wolfe's classification, and statistical analysis was by conditional logistic regression. Relative to the N1 pattern, the odds ratios of having an invasive breast cancer associated with the P2 and DY patterns were 1.8 and 1.4, respectively. In addition, the odd ratios of having an invasive grade 3 breast cancer associated with the P2 and DY patterns were 2.8 and 3.9, respectively. Relative to the combined N1/P1 pattern, the odd ratios of having a breast cancer smaller than 14 mm, 15-29 mm, or larger than 30 mm associated with the combined high-risk P2/DY pattern (P2 + DY) were 1.2, 1.6, and 2.0, respectively. Finally, women with the P2/DY pattern were twice as likely to have a breast cancer which had already spread to the axillary nodes, compared to women with women with the N1/P1 pattern (odds ratios of 2.1 and 1.4, respectively). Our results confirm previous findings suggesting that mammographic parenchymal patterns may serve as indicators of risk for breast cancer. Our results also suggest that mammographic parenchymal patterns are associated with the stage at which breast cancer is detected. (orig.)

  15. Up-regulated proteins in the fluid bathing the tumour cell microenvironment as potential serological markers for early detection of cancer of the breast

    DEFF Research Database (Denmark)

    Gromov, Pavel; Gromova, Irina; Bunkenborg, Jakob

    2010-01-01

    -based proteomics in combination with mass spectrometry and immunohistochemistry (IHC) of the tumour interstitial fluids (TIF) and normal interstitial fluids (NIF) collected from 69 prospective breast cancer patients. The goal of this study was to identify abundant cancer up-regulated proteins that are externalised...... in the TIF, some of which were confirmed by IHC. In the second phase, we carried out a systematic computer assisted analysis of the 2D gels of the remaining 68 TIF samples in order to identify TIF 46 up-regulated proteins that were deregulated in 90% or more of all the available TIFs, thus representing...

  16. Prospective MRI assessment for invasive lobular breast cancer. Correlation with tumour size at histopathology and influence on surgical management

    International Nuclear Information System (INIS)

    Muttalib, M.; Ibrahem, R.; Khashan, A.S.; Hajaj, M.

    2014-01-01

    Aim: To evaluate the performance of breast magnetic resonance imaging (MRI) in determining the size of invasive lobular carcinoma (ILC) compared to histopathology, and its influence on breast surgical management. Materials and methods: Prospective evaluation was undertaken of standardized contrast-enhanced MRI images of 51 consecutive women over an 18 month period with pure ILC or with lobular features as the dominant subtype on breast core biopsy. Image interpretation was performed by one consultant radiologist (M.H.). The lesion size at MRI was compared with the size at final histopathology after surgical excision using a Bland–Altman agreement plot. Results: Of the 51 prospectively imaged consecutive women, seven were excluded as they had diffuse ILC. The remaining 44 patients had a mean histological tumour size of 34.9 mm (range 4–77 mm). MRI underestimated tumour size in 26 (59.1%) cases. In 21 (47.7%) patients, this discrepancy was small, ranging up to 16 mm. The largest underestimation occurred in five (11.4%) cases with a difference ranging between 31 and 48 mm. Fifteen (34.1%) tumours were overestimated by MRI where the discrepancy ranged up to 22 mm. In three (6.8%) patients MRI and histological size matched. The Bland–Altman agreement plot demonstrated that in 95% of cases the size at histopathology will be between 0.36 and 2.31 times the MRI size at extremes. MRI correlated better with histopathology in tumours up to T2 (<5 cm) size leading to a change in surgical management for nine of the 44 (20.5%) patients. Conclusion: MRI enables surgical management decisions to be made with increased confidence in patients with ILC up to T2 size

  17. Breast cancer detection using time reversal

    Science.gov (United States)

    Sheikh Sajjadieh, Mohammad Hossein

    Breast cancer is the second leading cause of cancer death after lung cancer among women. Mammography and magnetic resonance imaging (MRI) have certain limitations in detecting breast cancer, especially during its early stage of development. A number of studies have shown that microwave breast cancer detection has potential to become a successful clinical complement to the conventional X-ray mammography. Microwave breast imaging is performed by illuminating the breast tissues with an electromagnetic waveform and recording its reflections (backscatters) emanating from variations in the normal breast tissues and tumour cells, if present, using an antenna array. These backscatters, referred to as the overall (tumour and clutter) response, are processed to estimate the tumour response, which is applied as input to array imaging algorithms used to estimate the location of the tumour. Due to changes in the breast profile over time, the commonly utilized background subtraction procedures used to estimate the target (tumour) response in array processing are impractical for breast cancer detection. The thesis proposes a new tumour estimation algorithm based on a combination of the data adaptive filter with the envelope detection filter (DAF/EDF), which collectively do not require a training step. After establishing the superiority of the DAF/EDF based approach, the thesis shows that the time reversal (TR) array imaging algorithms outperform their conventional conterparts in detecting and localizing tumour cells in breast tissues at SNRs ranging from 15 to 30dB.

  18. Breast spindle cell tumours: about eight cases

    Directory of Open Access Journals (Sweden)

    Abd El All Howayda S

    2006-07-01

    Full Text Available Abstract Background Breast spindle cell tumours (BSCTs, although rare, represent a heterogeneous group with different treatment modalities. This work was undertaken to evaluate the utility of fine needle aspiration cytology (FNAC, histopathology and immunohistochemistry (IHC in differentiating BSCTs. Methods FNAC of eight breast masses diagnosed cytologically as BSCTs was followed by wide excision biopsy. IHC using a panel of antibodies against vimentin, pan-cytokeratin, s100, desmin, smooth muscle actin, CD34, and CD10 was evaluated to define their nature. Results FNAC defined the tumors as benign (n = 4, suspicious (n = 2 and malignant (n = 3, based on the cytopathological criteria of malignancy. Following wide excision biopsy, the tumors were reclassified into benign (n = 5 and malignant (n = 3. In the benign group, the diagnosis was raised histologically and confirmed by IHC for 3 cases (one spindle cell lipoma, one myofibroblastoma and one leiomyoma. For the remaining two cases, the diagnosis was set up after IHC (one fibromatosis and one spindle cell variant of adenomyoepithelioma. In the malignant group, a leiomyosarcoma was diagnosed histologically, while IHC was crucial to set up the diagnosis of one case of spindle cell carcinoma and one malignant myoepithelioma. Conclusion FNAC in BSCTs is an insufficient tool and should be followed by wide excision biopsy. The latter technique differentiate benign from malignant BSCTs and is able in 50% of the cases to set up the definite diagnosis. IHC is of value to define the nature of different benign lesions and is mandatory in the malignant ones for optimal treatment. Awareness of the different types of BSCTs prevents unnecessary extensive therapeutic regimes.

  19. Development of a Tumour Growth Inhibition Model to Elucidate the Effects of Ritonavir on Intratumoural Metabolism and Anti-tumour Effect of Docetaxel in a Mouse Model for Hereditary Breast Cancer.

    Science.gov (United States)

    Yu, Huixin; Hendrikx, Jeroen J M A; Rottenberg, Sven; Schellens, Jan H M; Beijnen, Jos H; Huitema, Alwin D R

    2016-03-01

    In a mouse tumour model for hereditary breast cancer, we previously explored the anti-cancer effects of docetaxel, ritonavir and the combination of both and studied the effect of ritonavir on the intratumoural concentration of docetaxel. The objective of the current study was to apply pharmacokinetic (PK)-pharmacodynamic (PD) modelling on this previous study to further elucidate and quantify the effects of docetaxel when co-administered with ritonavir. PK models of docetaxel and ritonavir in plasma and in tumour were developed. The effect of ritonavir on docetaxel concentration in the systemic circulation of Cyp3a knock-out mice and in the implanted tumour (with inherent Cyp3a expression) was studied, respectively. Subsequently, we designed a tumour growth inhibition model that included the inhibitory effects of both docetaxel and ritonavir. Ritonavir decreased docetaxel systemic clearance with 8% (relative standard error 0.4%) in the co-treated group compared to that in the docetaxel only-treated group. The docetaxel concentration in tumour tissues was significantly increased by ritonavir with mean area under the concentration-time curve 2.5-fold higher when combined with ritonavir. Observed tumour volume profiles in mice could be properly described by the PK/PD model. In the co-treated group, the enhanced anti-tumour effect was mainly due to increased docetaxel tumour concentration; however, we demonstrated a small but significant anti-tumour effect of ritonavir addition (p value effect observed when docetaxel is combined with ritonavir is mainly caused by enhanced docetaxel tumour concentration and to a minor extent by a direct anti-tumour effect of ritonavir.

  20. Targeted intraoperative radiotherapy tumour bed boost during breast-conserving surgery after neoadjuvant chemotherapy

    Energy Technology Data Exchange (ETDEWEB)

    Kolberg, Hans-Christian; Akpolat-Basci, Leyla; Stephanou, Miltiades [Marienhospital Bottrop gGmbH, Department of Gynecology and Obstetrics, Bottrop (Germany); Loevey, Gyoergy [BORAD, Bottrop (Germany); Fasching, Peter A. [University of Erlangen, Erlangen (Germany); Untch, Michael [Helios Klinikum Berlin-Buch, Berlin (Germany); Liedtke, Cornelia [University Hospital Schleswig-Holstein/Campus Luebeck, Luebeck (Germany); Bulsara, Max [University of Notre Dame, Fremantle (Australia); University College, London (United Kingdom); Vaidya, Jayant S. [University College, London (United Kingdom)

    2017-01-15

    The use of targeted intraoperative radiotherapy (TARGIT-IORT) as a tumour bed boost during breast-conserving surgery (BCS) for breast cancer has been reported since 1998. We present its use in patients undergoing breast conservation following neoadjuvant therapy (NACT). In this retrospective study involving 116 patients after NACT we compared outcomes of 61 patients who received a tumour bed boost with IORT during lumpectomy versus 55 patients treated in the previous 13 months with external (EBRT) boost. All patients received whole breast radiotherapy. Local recurrence-free survival (LRFS), disease-free survival (DFS), distant disease-free survival (DDFS), breast cancer mortality (BCM), non-breast cancer mortality (NBCM) and overall mortality (OS) were compared. Median follow up was 49 months. The differences in LRFS, DFS and BCM were not statistically significant. The 5-year Kaplan-Meier estimate of OS was significantly better by 15% with IORT: IORT 2 events (96.7%, 95%CI 87.5-99.2), EBRT 9 events (81.7%, 95%CI 67.6-90.1), hazard ratio (HR) 0.19 (0.04-0.87), log rank p = 0.016, mainly due to a reduction of 10.1% in NBCM: IORT 100%, EBRT 89.9% (77.3-95.7), HR (not calculable), log rank p = 0.015. The DDFS was as follows: IORT 3 events (95.1%, 85.5-98.4), EBRT 12 events (69.0%, 49.1-82.4), HR 0.23 (0.06-0.80), log rank p = 0.012. IORT during lumpectomy after neoadjuvant chemotherapy as a tumour bed boost appears to give results that are not worse than external beam radiotherapy boost. These data give further support to the inclusion of such patients in the TARGIT-B (boost) randomised trial that is testing whether IORT boost is superior to EBRT boost. (orig.) [German] Die intraoperative Radiotherapie (TARGIT-IORT) als vorgezogener Boost im Rahmen der brusterhaltenden Therapie (BET) ist seit 1998 Gegenstand der wissenschaftlichen Diskussion. Wir praesentieren Daten zum Einsatz der IORT bei der BET nach neoadjuvanter Therapie (NACT). In diese retrospektive Analyse

  1. Identification of novel LRH-1 target genes in breast cancer cells

    OpenAIRE

    Zhao, Zhe

    2017-01-01

    The orphan nuclear receptor liver receptor homolog-1 (LRH-1) plays important roles in embryonic development, lipid homeostasis and steroidogenesis, and has been implicated in driving several cancers. In breast cancer, LRH-1 is expressed in tumour epithelial cells of invasive ductal carcinomas. We hypothesized that LRH-1 regulates epithelial cell proliferation and invasiveness to drive breast tumour progression. The overall goal of this study was to identify molecular mechanisms regulated by L...

  2. Menopausal status dependence of the timing of breast cancer recurrence after surgical removal of the primary tumour

    International Nuclear Information System (INIS)

    Demicheli, Romano; Bonadonna, Gianni; Hrushesky, William JM; Retsky, Michael W; Valagussa, Pinuccia

    2004-01-01

    Information on the metastasis process in breast cancer patients undergoing primary tumour removal may be extracted from an analysis of the timing of clinical recurrence. The hazard rate for local-regional and/or distant recurrence as the first event during the first 4 years after surgery was studied in 1173 patients undergoing mastectomy alone as primary treatment for operable breast cancer. Subset analyses were performed according to tumour size, axillary nodal status and menopausal status. A sharp two-peaked hazard function was observed for node-positive pre-menopausal patients, whereas results from node-positive post-menopausal women always displayed a single broad peak. The first narrow peak among pre-menopausal women showed a very steep rise to a maximum about 8–10 months after mastectomy. The second peak was considerably broader, reaching its maximum at 28–30 months. Post-menopausal patients displayed a wide, nearly symmetrical peak with maximum risk at about 18–20 months. Peaks displayed increasing height with increasing axillary lymph node involvement. No multi-peaked pattern was evident for either pre-menopausal or post-menopausal node-negative patients; however, this finding should be considered cautiously because of the limited number of events. Tumour size influenced recurrence risk but not its timing. Findings resulting from the different subsets of patients were remarkably coherent and each observed peak maintained the same position on the time axis in all analysed subsets. The risk of early recurrence for node positive patients is dependent on menopausal status. The amount of axillary nodal involvement and the tumour size modulate the risk value at any given time. For pre-menopausal node-positive patients, the abrupt increase of the first narrow peak of the recurrence risk suggests a triggering event that synchronises early risk. We suggest that this event is the surgical removal of the primary tumour. The later, broader, more symmetrical risk

  3. Targeting tissue factor on tumour cells and angiogenic vascular endothelial cells by factor VII-targeted verteporfin photodynamic therapy for breast cancer in vitro and in vivo in mice

    International Nuclear Information System (INIS)

    Hu, Zhiwei; Rao, Benqiang; Chen, Shimin; Duanmu, Jinzhong

    2010-01-01

    The objective of this study was to develop a ligand-targeted photodynamic therapy (tPDT) by conjugating factor VII (fVII) protein with photosensitiser verteporfin in order to overcome the poor selectivity and enhance the effect of non-targeted PDT (ntPDT) for cancer. fVII is a natural ligand for receptor tissue factor (TF) with high affinity and specificity. The reason for targeting receptor TF for the development of tPDT is that TF is a common but specific target on angiogenic tumour vascular endothelial cells (VEC) and many types of tumour cells, including solid tumours and leukaemia. Murine factor VII protein (mfVII) containing a mutation (Lys341Ala) was covalently conjugated via a cross linker EDC with Veterporfin (VP) that was extracted from liposomal Visudyne, and then free VP was separated by Sephadex G50 spin columns. fVII-tPDT using mfVII-VP conjugate, compared to ntPDT, was tested in vitro for the killing of breast cancer cells and VEGF-stimulated VEC and in vivo for inhibiting the tumour growth of breast tumours in a mouse xenograft model. We showed that: (i) fVII protein could be conjugated with VP without affecting its binding activity; (ii) fVII-tPDT could selectively kill TF-expressing breast cancer cells and VEGF-stimulated angiogenic HUVECs but had no side effects on non-TF expressing unstimulated HUVEC, CHO-K1 and 293 cells; (iii) fVII targeting enhanced the effect of VP PDT by three to four fold; (iii) fVII-tPDT induced significantly stronger levels of apoptosis and necrosis than ntPDT; and (iv) fVII-tPDT had a significantly stronger effect on inhibiting breast tumour growth in mice than ntPDT. We conclude that the fVII-targeted VP PDT that we report here is a novel and effective therapeutic with improved selectivity for the treatment of breast cancer. Since TF is expressed on many types of cancer cells including leukaemic cells and selectively on angiogenic tumour VECs, fVII-tPDT could have broad therapeutic applications for other solid cancers

  4. In silico design and performance of peptide microarrays for breast cancer tumour-auto-antibody testing

    Directory of Open Access Journals (Sweden)

    Andreas Weinhäusel

    2012-06-01

    Full Text Available The simplicity and potential of minimally invasive testing using sera from patients makes auto-antibody based biomarkers a very promising tool for use in cancer diagnostics. Protein microarrays have been used for the identification of such auto-antibody signatures. Because high throughput protein expression and purification is laborious, synthetic peptides might be a good alternative for microarray generation and multiplexed analyses. In this study, we designed 1185 antigenic peptides, deduced from proteins expressed by 642 cDNA expression clones found to be sero-reactive in both breast tumour patients and controls. The sero-reactive proteins and the corresponding peptides were used for the production of protein and peptide microarrays. Serum samples from females with benign and malignant breast tumours and healthy control sera (n=16 per group were then analysed. Correct classification of the serum samples on peptide microarrays were 78% for discrimination of ‘malignant versus healthy controls’, 72% for ‘benign versus malignant’ and 94% for ‘benign versus controls’. On protein arrays, correct classification for these contrasts was 69%, 59% and 59%, respectively. The over-representation analysis of the classifiers derived from class prediction showed enrichment of genes associated with ribosomes, spliceosomes, endocytosis and the pentose phosphate pathway. Sequence analyses of the peptides with the highest sero-reactivity demonstrated enrichment of the zinc-finger domain. Peptides’ sero-reactivities were found negatively correlated with hydrophobicity and positively correlated with positive charge, high inter-residue protein contact energies and a secondary structure propensity bias. This study hints at the possibility of using in silico designed antigenic peptide microarrays as an alternative to protein microarrays for the improvement of tumour auto-antibody based diagnostics.

  5. Radiological appearances of papillary breast lesions

    International Nuclear Information System (INIS)

    Brookes, M.J.; Bourke, A.G.

    2008-01-01

    This review illustrates the varied appearances of benign and malignant papillary breast tumours, as identified by a breast cancer-screening programme. The commonest mammographic appearance of a papillary tumour is as a soft-tissue mass, with calcification present in less than half of cases. When calcification is present the pattern is variable, but clusters of pleomorphic calcification can occur, sometimes resembling the mammographic appearance of invasive ductal carcinoma. Ultrasonography of papillary lesions typically shows a solid, oval, intraductal mass, often associated with duct dilatation. A cystic component is also commonly seen, and lesions may appear hypervascular on colour Doppler ultrasound. Magnetic resonance imaging (MRI) has a high sensitivity, but low specificity for detecting papillary tumours, and is useful in establishing the extent and distribution of lesions in patients with multiple papillomatosis. Despite a benign histology on core biopsy, an argument exists for complete surgical excision of all papillary tumours, as a significant proportion of papillomas will contain foci of atypia or overt malignant change

  6. Radiological appearances of papillary breast lesions

    Energy Technology Data Exchange (ETDEWEB)

    Brookes, M.J. [Sir Charles Gairdner Hospital, Nedlands, Perth, Western Australia (Australia)], E-mail: mattbrookes@doctors.org.uk; Bourke, A.G. [Sir Charles Gairdner Hospital, Nedlands, Perth, Western Australia (Australia)

    2008-11-15

    This review illustrates the varied appearances of benign and malignant papillary breast tumours, as identified by a breast cancer-screening programme. The commonest mammographic appearance of a papillary tumour is as a soft-tissue mass, with calcification present in less than half of cases. When calcification is present the pattern is variable, but clusters of pleomorphic calcification can occur, sometimes resembling the mammographic appearance of invasive ductal carcinoma. Ultrasonography of papillary lesions typically shows a solid, oval, intraductal mass, often associated with duct dilatation. A cystic component is also commonly seen, and lesions may appear hypervascular on colour Doppler ultrasound. Magnetic resonance imaging (MRI) has a high sensitivity, but low specificity for detecting papillary tumours, and is useful in establishing the extent and distribution of lesions in patients with multiple papillomatosis. Despite a benign histology on core biopsy, an argument exists for complete surgical excision of all papillary tumours, as a significant proportion of papillomas will contain foci of atypia or overt malignant change.

  7. Combining phenotypic and proteomic approaches to identify membrane targets in a ‘triple negative’ breast cancer cell type

    Directory of Open Access Journals (Sweden)

    Rust Steven

    2013-02-01

    Full Text Available Abstract Background The continued discovery of therapeutic antibodies, which address unmet medical needs, requires the continued discovery of tractable antibody targets. Multiple protein-level target discovery approaches are available and these can be used in combination to extensively survey relevant cell membranomes. In this study, the MDA-MB-231 cell line was selected for membranome survey as it is a ‘triple negative’ breast cancer cell line, which represents a cancer subtype that is aggressive and has few treatment options. Methods The MDA-MB-231 breast carcinoma cell line was used to explore three membranome target discovery approaches, which were used in parallel to cross-validate the significance of identified antigens. A proteomic approach, which used membrane protein enrichment followed by protein identification by mass spectrometry, was used alongside two phenotypic antibody screening approaches. The first phenotypic screening approach was based on hybridoma technology and the second was based on phage display technology. Antibodies isolated by the phenotypic approaches were tested for cell specificity as well as internalisation and the targets identified were compared to each other as well as those identified by the proteomic approach. An anti-CD73 antibody derived from the phage display-based phenotypic approach was tested for binding to other ‘triple negative’ breast cancer cell lines and tested for tumour growth inhibitory activity in a MDA-MB-231 xenograft model. Results All of the approaches identified multiple cell surface markers, including integrins, CD44, EGFR, CD71, galectin-3, CD73 and BCAM, some of which had been previously confirmed as being tractable to antibody therapy. In total, 40 cell surface markers were identified for further study. In addition to cell surface marker identification, the phenotypic antibody screening approaches provided reagent antibodies for target validation studies. This is illustrated

  8. A comparative study between mixed-type tumours from human salivary and canine mammary glands

    International Nuclear Information System (INIS)

    Genelhu, Marisa CLS; Cardoso, Sérgio V; Gobbi, Helenice; Cassali, Geovanni D

    2007-01-01

    In comparative pathology, canine mammary tumours have special interest because of their similarities with human breast cancer. Mixed tumours are uncommon lesions in the human breast, but they are found most frequently in the mammary gland of the female dogs and in the human salivary glands. The aim of the study was to compare clinical, morphological and immunohistochemical features of human salivary and canine mammary gland mixed tumours, in order to evaluate the latter as an experimental model for salivary gland tumours. Ten examples of each mixed tumour type (human pleomorphic adenoma and carcinomas ex-pleomorphic adenomas and canine mixed tumour and metaplastic carcinoma) were evaluated. First, clinical and morphologic aspects of benign and malignant variants were compared between the species. Then, streptavidin-biotin-peroxidase immunohistochemistry was performed to detect the expression of cytokeratins, vimentin, p63 protein, estrogen receptor, β-catenin, and E-cadherin. After standardization, similar age and site distributions were observed in human and canine tumours. Histological similarities were identified in the comparison of the benign lesions as well. Metaplastic carcinomas also resembled general aspects of carcinomas ex-pleomorphic adenomas in morphological evaluation. Additionally, immunohistochemical staining further presented similar antigenic expression between lesions. There are many similar features between human salivary and canine mammary gland mixed tumours. This observation is of great relevance for those interested in the study and management of salivary gland tumours, since canine lesions may constitute useful comparative models for their investigations

  9. Increasing the diagnosis of multifocal primary breast cancer by the use of bilateral whole-breast ultrasound

    International Nuclear Information System (INIS)

    Wilkinson, L.S.; Given-Wilson, R.; Hall, T.; Potts, H.; Sharma, A.K.; Smith, E.

    2005-01-01

    AIM: The aim of this study was to evaluate the contribution of bilateral whole-breast ultrasound (BBUS) to the diagnosis and management of women with newly diagnosed breast cancer. METHODS: Over a period of 6 months, 102 women presenting with breast cancer underwent BBUS. Data were collected on clinical findings, radiology, histology and surgical outcome. These women were compared with a control group of 124 women presenting over a similar 6-month period 1 year previously, who had undergone targeted breast ultrasound. RESULTS: Multicentric/multifocal tumours were demonstrated in 35 (34%) of the 102 participants and in 18 (15%) of the 124 controls, a statistically significant difference (Fisher's exact test, p=0.001). Multiple tumours were diagnosed preoperatively in 18% of the study population compared with 8% of the controls, and BBUS identified invasive multifocal/multicentric tumours in significantly more women in the study population (11 versus 1 control) (Fisher's exact test, p=0.019). Contralateral cancer was diagnosed in 4 women in the study population and none in the control population (Fisher's exact test, p=0.040). Surgical review showed that the surgical management changed significantly in 8% (95% confidence interval 4 to 14%) of cases in the study population following BBUS. The increase in the number of women undergoing benign biopsies in the study population (10 versus 5 controls) was not statistically significant (Fisher's exact test, p=0.11). CONCLUSION: BBUS increased the preoperative diagnosis of multiple tumours in women presenting with primary breast cancer, resulting in a management change in 8% of cases

  10. Synchronous and Metachronous Malignant Tumours expect the un-expected

    International Nuclear Information System (INIS)

    Mehdi, I.; Shah, A.H.; Moona, M.S.; Verma, K.; Abussa, A.; Elramih, R.; El-Hashmi, H.

    2010-01-01

    Objective: To evaluate occurrence of synchronous and metachronous malignant tumours, to find tumour types, age group, and relationship to treatment received. Methods: Previously diagnosed first primary tumour cases experiencing a synchronous or metachronous tumour, seen at AOI from February 2003 to August 2009 (78 months) were included. The cases were analyzed for morphology/histology of first primary tumour, age and gender of patient, treatment received for first tumour, time interval between the first and second primary tumour, morphology/histology of second tumour, and the treatment conferred for second tumour. Results: The second synchronous and metachronous tumours were 46/4025 (1.14%), in 18 males and 28 females (M:F 1:1.6). The age range was 16-75 years (median 43 years). The follow up time was 24-150 months. The time to second primary tumour was 2-132 months. The first primary tumours were breast, ovary, GIT and urinary bladder. The patients received surgery, radiotherapy, chemotherapy, and hormonal therapy alone or as multi-modality treatment for the first tumours. The frequent second tumours were breast, ovary and Gastro Intestinal tumours. Conclusion: It is imperative that patients with a primary malignant tumour should be thoroughly, closely, and regularly followed. Genetic counseling, risk estimation, cancer screening and hemo prevention must be emphasized. Every subsequent occurring tumour should be biopsied. The effect of first tumour on the second or vice versa are still not fully understood and need exploration. The second primary tumour is usually more aggressive, treatment resistant, and metastasizes early requiring a more aggressive treatment strategy. (author)

  11. Mast cells and eosinophils in invasive breast carcinoma

    International Nuclear Information System (INIS)

    Amini, Rose-Marie; Aaltonen, Kirsimari; Nevanlinna, Heli; Carvalho, Ricardo; Salonen, Laura; Heikkilä, Päivi; Blomqvist, Carl

    2007-01-01

    Inflammatory cells in the tumour stroma has gained increasing interest recently. Thus, we aimed to study the frequency and prognostic impact of stromal mast cells and tumour infiltrating eosinophils in invasive breast carcinomas. Tissue microarrays containing 234 cases of invasive breast cancer were prepared and analysed for the presence of stromal mast cells and eosinophils. Tumour infiltrating eosinophils were counted on hematoxylin-eosin slides. Immunostaining for tryptase was done and the total number of mast cells were counted and correlated to the proliferation marker Ki 67, positivity for estrogen and progesterone receptors, clinical parameters and clinical outcome. Stromal mast cells were found to correlate to low grade tumours and estrogen receptor positivity. There was a total lack of eosinophils in breast cancer tumours. A high number of mast cells in the tumours correlated to low-grade tumours and estrogen receptor positivity. Eosinophils are not tumour infiltrating in breast cancers

  12. Giant fibroadenoma presenting like fungating breast cancer in a ...

    African Journals Online (AJOL)

    Background: Giant fibroadenoma of the breast is a rare benign breast tumour which seldom grows to a giant size, it is even rarer for this benign tumour to grow rapidly, ulcerate spontaneously and present like a fungating breast tumour in a way mimicking breast cancer. Case presentation: This is a presentation of a 14 year ...

  13. Giant desmoid tumour of the thorax following latissimus dorsi and implant breast reconstruction: case report and review of the literature

    LENUS (Irish Health Repository)

    Collins, AM

    2017-03-01

    The case of a giant thoracic desmoid tumour in a 44-year-old woman, who presented two years following a breast reconstruction with a latissimus dorsi (LD) flap and implant, is reported. Clinical findings included a rapidly growing, painless mass. Computed tomography (CT) suggested skin and intercostal soft tissue invasion. The tumour was resected en bloc with the LD muscle, implant capsule and underlying rib segments. The resultant thoracic and abdominal wall defects were reconstructed with Dualmesh® and polypropylene meshes respectively. There was no evidence of recurrence at thirty-six months follow-up.

  14. The pathology of familial breast cancer: Morphological aspects

    International Nuclear Information System (INIS)

    Lakhani, Sunil R

    1999-01-01

    A small proportion of breast cancers are due to a heritable predisposition. Recently, two predisposition genes, BRCA1 and BRCA2, have been identified and cloned. The morphological features of tumours from patients harbouring mutations in the BRCA1 and BRCA2 genes differ from each other and from sporadic breast cancers. Both are of higher grade than are sporadic cases. An excess of medullary/atypical medullary carcinoma has been reported in patients with BRCA1 mutations. Multifactorial analysis, however, shows that the only features independently associated with BRCA1 mutations are a high mitotic count, pushing tumour margins and a lymphocytic infiltrate. For BRCA2 mutation, an association with tubular/lobular carcinoma has been suggested, but not substantiated in a larger Breast Cancer Linkage Consortium study. In multifactorial analysis, the independent features were a lack of tubule formation and pushing tumour margins only. The morphological analysis has implications for clinical management of patients

  15. Angiogenesis and lymphangiogenesis are downregulated in primary breast cancer

    Science.gov (United States)

    Boneberg, E-M; Legler, D F; Hoefer, M M; Öhlschlegel, C; Steininger, H; Füzesi, L; Beer, G M; Dupont-Lampert, V; Otto, F; Senn, H-J; Fürstenberger, G

    2009-01-01

    Background: Angiogenesis and lymphangiogenesis are considered to play key roles in tumour growth, progression and metastasis. However, targeting tumour angiogenesis in clinical trials showed only modest efficacy. We therefore scrutinised the concept of tumour angiogenesis and lymphangiogenesis by analysing the expression of crucial markers involved in these processes in primary breast cancer. Methods: We analysed the expression of angiogenic, lymphangiogenic or antiangiogenic factors, their respective receptors and specific markers for endothelial and lymphendothelial cells by quantitative real-time RT-PCR in primary breast cancer and compared the expression profiles to non-cancerous, tumour-adjacent tissues and breast tissues from healthy women. Results: We found decreased mRNA amounts of major angiogenic and lymphangiogenic factors in tumour compared to healthy tissues, whereas antiangiogenic factors were upregulated. Concomitantly, angiogenic and lymphangiogenic receptors were downregulated in breast tumours. This antiangiogenic, antilymphangiogenic microenvironment was even more pronounced in aggressive tumours and accompanied by reduced amounts of endothelial and lymphatic endothelial cell markers. Conclusion: Primary breast tumours are not a site of highly active angiogenesis and lymphangiogenesis. Selection for tumour cells that survive with minimal vascular supply may account for this observation in clinical apparent tumours. PMID:19672262

  16. Molecular-based tumour subtypes of canine mammary carcinomas assessed by immunohistochemistry

    Directory of Open Access Journals (Sweden)

    Sarli Giuseppe

    2010-01-01

    Full Text Available Abstract Background Human breast cancer is classified by gene expression profile into subtypes consisting of two hormone (oestrogen and/or progesterone receptor-positive types (luminal-like A and luminal-like B and three hormone receptor-negative types [human epidermal growth factor receptor 2-expressing, basal-like, and unclassified ("normal-like"]. Immunohistochemical surrogate panels are also proposed to potentially identify the molecular-based groups. The present study aimed to apply an immunohistochemical panel (anti-ER, -PR, -ERB-B2, -CK 5/6 and -CK14 in a series of canine malignant mammary tumours to verify the molecular-based classification, its correlation with invasion and grade, and its use as a prognostic aid in veterinary practice. Results Thirty-five tumours with luminal pattern (ER+ and PR+ were subgrouped into 13 A type and 22 B type, if ERB-B2 positive or negative. Most luminal-like A and basal-like tumours were grade 1 carcinomas, while the percentage of luminal B tumours was higher in grades 2 and 3 (Pearson Chi-square P = 0.009. No difference in the percentage of molecular subtypes was found between simple and complex/mixed carcinomas (Pearson Chi-square P = 0.47. No significant results were obtained by survival analysis, even if basal-like tumours had a more favourable prognosis than luminal-like lesions. Conclusion The panel of antibodies identified only three tumour groups (luminal-like A and B, and basal-like in the dog. Even though canine mammary tumours may be a model of human breast cancer, the existence of the same carcinoma molecular subtypes in women awaits confirmation. Canine mammary carcinomas show high molecular heterogeneity, which would benefit from a classification based on molecular differences. Stage and grade showed independent associations with survival in the multivariate regression, while molecular subtype grouping and histological type did not show associations. This suggests that caution should be

  17. Real-time RT-PCR systems for CTC detection from blood samples of breast cancer and gynaecological tumour patients (Review).

    Science.gov (United States)

    Andergassen, Ulrich; Kölbl, Alexandra C; Mahner, Sven; Jeschke, Udo

    2016-04-01

    Cells, which detach from a primary epithelial tumour and migrate through lymphatic vessels and blood stream are called 'circulating tumour cells'. These cells are considered to be the main root of remote metastasis and are correlated to a worse prognosis concerning progression-free and overall survival of the patients. Therefore, the detection of the minimal residual disease is of great importance regarding therapeutic decisions. Many different detection strategies are already available, but only one method, the CellSearch® system, reached FDA approval. The present review focusses on the detection of circulating tumour cells by means of real-time PCR, a highly sensitive method based on differences in gene expression between normal and malignant cells. Strategies for an enrichment of tumour cells are mentioned, as well as a large panel of potential marker genes. Drawbacks and advantages of the technique are elucidated, whereas, the greatest advantage might be, that by selection of appropriate marker genes, also tumour cells, which have already undergone epithelial to mesenchymal transition can be detected. Finally, the application of real-time PCR in different gynaecological malignancies is described, with breast cancer being the most studied cancer entity.

  18. Giant fibroadenoma presenting like fungating breast cancer in a Nigerian teenager.

    Science.gov (United States)

    Arowolo, O A; Akinkuolie, A A; Adisa, A O; Obonna, G C; Olasode, B J

    2013-03-01

    Giant fibroadenoma of the breast is a rare benign breast tumour which seldom grows to a giant size, it is even rarer for this benign tumour to grow rapidly, ulcerate spontaneously and present like a fungating breast tumour in a way mimicking breast cancer. This is a presentation of a 14 year old premenarchal girl with a massive ulcerating and fungating left breast mass that was initially thought to be a fungating locally advanced breast carcinoma on clinical examination. Further examination of the morphology of the resected surgical specimen and histological examination confirmed it to be giant fibroadenoma of the breast. It was successfully managed by partial mastectomy and breast reconstruction with an excellent result and a high degree of patient satisfaction was achieved. Though a rare clinical entity benign breast tumour can present like a fungating breast cancer and this must be bore in mind especially in young adolescent patients presenting with ulcerating breast tumour.

  19. Glutathione S-transferase M1 null genotype: lack of association with tumour characteristics and survival in advanced breast cancer

    International Nuclear Information System (INIS)

    Lizard-Nacol, Sarab; Coudert, Bruno; Colosetti, Pascal; Riedinger, Jean-Marc; Fargeot, Pierre; Brunet-Lecomte, Patrick

    1999-01-01

    Glutathione S-transferase (GST)M1, a member of the μ class GST gene family, has been shown to be polymorphic because of a partial gene deletion. This results in a failure to express the GSTM1 gene in 50-60% of individuals. Several studies have demonstrated a possible link with the GSTM1-null genotype and susceptibility to cancer. Furthermore, a GSTM1 isoenzyme has been positively associated with protective effect against mutagenic drugs, such as alkylating agents and anthracyclines. To determine whether GSTM1 polymorphisms are associated with tumour characteristics and survival in advanced breast cancer patients, and whether it may constitute a prognostic factor. We genotyped 92 patients receiving primary chemotherapy, which included cyclophosphamide, doxorubicine and 5-fluorouracil. The relationships between allelism at GSTM1 and clinicopathological parameters including age, menopausal status, tumour size, grade hormone receptors, involved nodes and p53 gene mutations were analysed. Of the patients with GSTM1-positive genotype, tissue samples obtained before and after treatment were available from 28 cases, allowing RNA extraction and GSTM1 expression by reverse transcription polymerase chain reaction. Relationships with clinical response to chemotherapy, and disease-free and overall survival were also evaluated. The data obtained was analysed using logistic regression to estimate the odds ratio and 95% confidence interval. Of 92 patients, 57.6% (n = 53) were classified as heritably GSTM1-deficient, and 42.4% (n = 39) were of the GSTM1-positive genotype. There were no statistically significant relationships between GSTM1-null genotype and the clinicopathological parameters analysed. No relationship was observed between GSTM1 RNA expression and objective clinical response to chemotherapy. Objective clinical response to chemotherapy was related only to clinical tumour size (P = 0.0177) and to the absence of intraductal carcinoma (P = 0.0013). GSTM1-null genotype

  20. GATA3 expression in triple-negative breast cancers.

    Science.gov (United States)

    Byrne, David J; Deb, Siddhartha; Takano, Elena A; Fox, Stephen B

    2017-07-01

    GATA-binding protein 3 (GATA3) is a well-studied transcription factor found to be essential in the development of luminal breast epithelium and has been identified in a variety of tumour types, including breast and urothelial carcinomas, making it a useful immunohistochemistry marker in the diagnosis of both primary and metastatic disease. We investigated GATA3 protein expression in a 106 primary triple-negative breast carcinomas (100 basal-like, six non-basal-like) using Cell Marque mouse monoclonal anti-GATA3 (L50-823). Reverse transcription-quantitative polymerase chain reaction (RT-qPCR) was used to quantify mRNA expression in 22 triple-negative breast cancers (TNBCs) (20 primary and two cell lines), four luminal (three primary and one cell line) and five human epidermal growth factor receptor 2 (HER2) (four primary and one cell line) amplified tumours. In 98 TNBCs where IHC was assessable, 47 (48%) had a 1+ or greater staining with 20 (21%) having high GATA3 expression when using a weighted scoring. Our study has demonstrated that GATA3 expression is common in primary triple-negative breast carcinomas. It also suggests that although GATA3 is an oestrogen receptor (ER) regulated gene, it still proves useful in differentiating between primary and metastatic tumours in patients with a history of breast cancer regardless of its molecular subtype. © 2017 John Wiley & Sons Ltd.

  1. Correlation between tumour characteristics, SUV measurements, metabolic tumour volume, TLG and textural features assessed with 18F-FDG PET in a large cohort of oestrogen receptor-positive breast cancer patients.

    Science.gov (United States)

    Lemarignier, Charles; Martineau, Antoine; Teixeira, Luis; Vercellino, Laetitia; Espié, Marc; Merlet, Pascal; Groheux, David

    2017-07-01

    The study was designed to evaluate 1) the relationship between PET image textural features (TFs) and SUVs, metabolic tumour volume (MTV), total lesion glycolysis (TLG) and tumour characteristics in a large prospective and homogenous cohort of oestrogen receptor-positive (ER+) breast cancer (BC) patients, and 2) the capability of those parameters to predict response to neoadjuvant chemotherapy (NAC). 171 consecutive patients with large or locally advanced ER+ BC without distant metastases underwent an 18 F-FDG PET examination before NAC. The primary tumour was delineated with an adaptive threshold segmentation method. Parameters of volume, intensity and texture (entropy, homogeneity, contrast and energy) were measured and compared with tumour characteristics determined on pre-treatment breast biopsy (Wilcoxon rank-sum test). The correlation between PET-derived parameters was determined using Spearman's coefficient. The relationship between PET features and pathological findings was determined using the Wilcoxon rank-sum test. Spearman's coefficients between SUV max and TFs were 0.43, 0.24, -0.43 and -0.15 respectively for entropy, homogeneity, energy and contrast; they were higher between MTV and TFs: 0.99, 0.86, -0.99 and -0.87. All TFs showed a significant association with the histological type (IDC vs. ILC; 0.02 < P < 0.03) but didn't with immunohistochemical characteristics. SUV max and TLG predicted the pathological response (P = 0.0021 and P = 0.02 respectively); TFs didn't (P: 0.27, 0.19, 0.94, 0.19 respectively for entropy, homogeneity, energy and contrast). The correlation of TFs was poor with SUV parameters and high with MTV. TFs showed a significant association with the histological type. Finally, while SUV max and TLG were able to predict response to NAC, TFs failed.

  2. Relationship between tumour size and response to neoadjuvant ...

    African Journals Online (AJOL)

    2018-03-16

    Mar 16, 2018 ... Introduction. Efforts to improve response of breast tumours to chemotherapy and maximize the benefit-to-adverse events ratio of chemotherapy include molecular subtyping to classify tumours, combined and cyclical use of chemotherapy and surgical de-bulking to stimulate proliferation. Molecular ...

  3. Development and evaluation of camptothecin loaded polymer stabilized nanoemulsion: Targeting potential in 4T1-breast tumour xenograft model.

    Science.gov (United States)

    Sugumaran, Abimanyu; Ponnusamy, Chandrasekar; Kandasamy, Palanivel; Krishnaswami, Venkateshwaran; Palanichamy, Rajaguru; Kandasamy, Ruckmani; Lakshmanan, Manikandan; Natesan, Subramanian

    2018-04-30

    Targeted delivery of anticancer agents is poised to improve cancer therapy, for which polymers can serve as targeting ligands or nanocarriers for chemotherapeutic agents. In this study, we have developed and evaluated the efficacy of a camptothecin (CPT)-loaded polymer stabilized nanoemulsion (PSNE) for the passive targeted delivery to breast cancer. Based on the pseudo-ternary phase diagrams, PSNEs were developed using capmul MCM:poloxamer 407 (4:1), solutol HS 15:simulsol P23 (1:2) and water. CPT polymer mixture was developed by solvent evaporation technique. The PSNEs were characterized for droplet size distribution, plasma protein adsorption, drug release, in-vivo targeting potential, hemolytic potential, cytotoxicity, genotoxicity, in-vivo biodistribution and CPT lactone ring stability. The developed PSNEs showed uniform droplet distribution, extended drug release (76.59±6.12% at 24h), acceptable hemolytic potential, significant cytotoxicity (IC 50 =176±4.3ng/mL) and genotoxicity against MCF-7 cancer cells but low DNA damage potential in human peripheral blood lymphocytes. The efficiency of PSNEs for the targeted delivery of CPT into the tumour regions was documented in 4T1-breast tumour xenografted BALB/c mice. In-vivo biodistribution study shows that 7105.84±568.46ng/g of CPT was passively targeted from PSNE to breast cancer tissue. About 80% of the lactone form was stable for 24h. Taken together, our study provides a promising strategy for developing PSNE-targeted drug delivery system for the breast cancer therapy. Copyright © 2017 Elsevier B.V. All rights reserved.

  4. Serum auto-antibody testing for early diagnosis of breast cancer

    International Nuclear Information System (INIS)

    Parvez, S.

    2012-01-01

    The aim of this thesis is generate prototype-tests suitable for randomized prospective validation of auto-antibody based diagnostic testing using serum samples. Tumours can stimulate the production of auto-antibodies against autologous cellular proteins known as TAAs (tumour associated antigens). This discovery has lead to a possibility of using the auto-antibodies as serological tools for the early diagnosis and management of breast cancer. The recombinant proteins expressed by the SEREX clones, identified from screenings of brain and lung tumour, were used for the production of the protein microarrays and macroarrays. The protein microarrays showed better correlation between the replicates of the serum samples used. The optimized protocols were used for the subsequent experiments. A sizable panel of 642 clone-proteins was selected by marker-screening on protein macroarrays with 38000 clones. These 642 clone-proteins were used to generate protein microarrays that differentiated serum samples from breast cancer patients and controls. Antigenic peptide motifs were identified by in-silico analysis of 642 clone-proteins and peptide arrays were generated using synthetically generated peptides. Comparative studies between protein microarrays and peptide microarrays were done using breast cancer and healthy control samples. Simultaneously, SEREX strategy was used for the identification of the immunogenic TAAs. I identified 192 cDNA expression clones derived from breast cancer tissue samples and the selection was done using breast cancer sera. The genes corresponding to these clones were found over-represented for the pathways that are known to be associated with cancers. These genes showed typical features of TAAs, like over-expression, mutations and fusion genes. (author)

  5. AMP-guided tumour-specific nanoparticle delivery via adenosine A1 receptor.

    Science.gov (United States)

    Dai, Tongcheng; Li, Na; Han, Fajun; Zhang, Hua; Zhang, Yuanxing; Liu, Qin

    2016-03-01

    Active targeting-ligands have been increasingly used to functionalize nanoparticles for tumour-specific clinical applications. Here we utilize nucleotide adenosine 5'-monophosphate (AMP) as a novel ligand to functionalize polymer-based fluorescent nanoparticles (NPs) for tumour-targeted imaging. We demonstrate that AMP-conjugated NPs (NPs-AMP) efficiently bind to and are following internalized into colon cancer cell CW-2 and breast cancer cell MDA-MB-468 in vitro. RNA interference and inhibitor assays reveal that the targeting effects mainly rely on the specific binding of AMP to adenosine A1 receptor (A1R), which is greatly up-regulated in cancer cells than in matched normal cells. More importantly, NPs-AMP specifically accumulate in the tumour site of colon and breast tumour xenografts and are further internalized into the tumour cells in vivo via tail vein injection, confirming that the high in vitro specificity of AMP can be successfully translated into the in vivo efficacy. Furthermore, NPs-AMP exhibit an active tumour-targeting behaviour in various colon and breast cancer cells, which is positively related to the up-regulation level of A1R in cancer cells, suggesting that AMP potentially suits for more extensive A1R-overexpressing cancer models. This work establishes AMP to be a novel tumour-targeting ligand and provides a promising strategy for future diagnostic or therapeutic applications. Copyright © 2016 Elsevier Ltd. All rights reserved.

  6. Can cell kinetic parameters predict the response of tumours to radiotherapy?

    Science.gov (United States)

    McNally, N J

    1989-11-01

    Three potential predictive assays of the repopulation component in tumour response to therapy are considered. (1) The DNA index can easily be measured. It is of prognostic value for cancers of certain sites, aneuploidy being a bad prognostic indicator. It is not strictly an indicator of cell proliferation. (2) The in vitro labelling index is of predictive value in early stage operable breast cancer and in head and neck cancer. In the former a high pretreatment labelling index can identify patients who could benefit from adjuvant chemotherapy. (3) The tumour potential doubling time (Tpot) can be measured rapidly following in vivo labelling with bromodeoxyuridine or iododeoxyuridine. We have measured Tpot in over 100 solid tumours with a success rate of about 75 per cent. Nearly 50 per cent of the tumours have a pre-treatment potential doubling time of 5 days or less. These would be suitable candidates for accelerated fractionation.

  7. Can cell kinetic parameters predict the response of tumours to radiotherapy?

    International Nuclear Information System (INIS)

    McNally, N.J.

    1989-01-01

    Three potential predictive assays of the repopulation component in tumour response to therapy are considered. (1) The DNA index can easily be measured. It is of prognostic value for cancers of certain sites, aneuploidy being a bad prognostic indicator. It is not strictly an indicator of cell proliferation. (2) The in vitro labelling index is of predictive value in early stage operable breast cancer and in head and neck cancer. In the former a high pretreatment labelling index can identify patients who could benefit from adjuvant chemotherapy. (3) The tumour potential doubling time can be measured rapidly following in vivo labelling with bromodeoxyuridine or iododeoxyuridine. The authors measured T pot in over 100 solid tumours with a success rate of about 75%. Nearly 50% of the tumours have a pre-treatment potential doubling time of 5 days or less. These would be suitable candidates for accelerated fractionation. (author)

  8. BAG3 promotes tumour cell proliferation by regulating EGFR signal transduction pathways in triple negative breast cancer.

    Science.gov (United States)

    Shields, Sarah; Conroy, Emer; O'Grady, Tony; McGoldrick, Alo; Connor, Kate; Ward, Mark P; Useckaite, Zivile; Dempsey, Eugene; Reilly, Rebecca; Fan, Yue; Chubb, Anthony; Matallanas, David Gomez; Kay, Elaine W; O'Connor, Darran; McCann, Amanda; Gallagher, William M; Coppinger, Judith A

    2018-03-20

    Triple-negative breast cancer (TNBC), is a heterogeneous disease characterised by absence of expression of the estrogen receptor (ER), progesterone receptor (PR) and lack of amplification of human epidermal growth factor receptor 2 (HER2). TNBC patients can exhibit poor prognosis and high recurrence stages despite early response to chemotherapy treatment. In this study, we identified a pro-survival signalling protein BCL2- associated athanogene 3 (BAG3) to be highly expressed in a subset of TNBC cell lines and tumour tissues. High mRNA expression of BAG3 in TNBC patient cohorts significantly associated with a lower recurrence free survival. The epidermal growth factor receptor (EGFR) is amplified in TNBC and EGFR signalling dynamics impinge on cancer cell survival and disease recurrence. We found a correlation between BAG3 and EGFR expression in TNBC cell lines and determined that BAG3 can regulate tumour cell proliferation, migration and invasion in EGFR expressing TNBC cells lines. We identified an interaction between BAG3 and components of the EGFR signalling networks using mass spectrometry. Furthermore, BAG3 contributed to regulation of proliferation in TNBC cell lines by reducing the activation of components of the PI3K/AKT and FAK/Src signalling subnetworks. Finally, we found that combined targeting of BAG3 and EGFR was more effective than inhibition of EGFR with Cetuximab alone in TNBC cell lines. This study demonstrates a role for BAG3 in regulation of distinct EGFR modules and highlights the potential of BAG3 as a therapeutic target in TNBC.

  9. Ultrasound-guided diffuse optical tomography (DOT) of invasive breast carcinoma: Does tumour total haemoglobin concentration contribute to the prediction of axillary lymph node status?

    Energy Technology Data Exchange (ETDEWEB)

    Zhu, Qingli, E-mail: qinglizhu@gmail.com [Department of Diagnostic Ultrasound, Peking Union Medical College Hospital, Chinese Academy of Medical Sciences, Shuaifuyuan 1, Dongcheng District, Beijing 100730 (China); Xiao, Mengsu, E-mail: xiaomengsu_2000@sina.com [Department of Diagnostic Ultrasound, Peking Union Medical College Hospital, Chinese Academy of Medical Sciences, Shuaifuyuan 1, Dongcheng District, Beijing 100730 (China); You, Shanshan, E-mail: shanshan_0531@sina.com [Department of Diagnostic Ultrasound, Peking Union Medical College Hospital, Chinese Academy of Medical Sciences, Shuaifuyuan 1, Dongcheng District, Beijing 100730 (China); Zhang, Jing, E-mail: zhang.jing1029@163.com [Department of Diagnostic Ultrasound, Peking Union Medical College Hospital, Chinese Academy of Medical Sciences, Shuaifuyuan 1, Dongcheng District, Beijing 100730 (China); Jiang, Yuxin, E-mail: yuxinjiangxh@yahoo.com.cn [Department of Diagnostic Ultrasound, Peking Union Medical College Hospital, Chinese Academy of Medical Sciences, Shuaifuyuan 1, Dongcheng District, Beijing 100730 (China); Lai, Xingjian, E-mail: lxjpumch@yahoo.com.cn [Department of Diagnostic Ultrasound, Peking Union Medical College Hospital, Chinese Academy of Medical Sciences, Shuaifuyuan 1, Dongcheng District, Beijing 100730 (China); Dai, Qing, E-mail: qingdai_2000@yahoo.com [Department of Diagnostic Ultrasound, Peking Union Medical College Hospital, Chinese Academy of Medical Sciences, Shuaifuyuan 1, Dongcheng District, Beijing 100730 (China)

    2012-11-15

    Objectives: To prospectively study the ultrasound-guided near-infrared diffuse optical tomography (DOT) findings of the total haemoglobin concentration (THC) detected in invasive breast carcinomas and its contribution to the prediction of axillary lymph node (LN) status. Methods: A total of 195 invasive breast carcinomas were prospectively studied with DOT before surgery. Lumpectomy or mastectomy with full axillary nodal dissection was performed. Tumour size and THC level were correlated with LN status by a logistic regression analysis. Results: One hundred twenty-four patients (63.59%) was LN(-) and 71 (36.41%) was LN(+). The average THC was significantly higher in the LN(+) group than in the LN(-) group (252.94 {+-} 69.19 {mu}mol/L versus 203.86 {+-} 83.13 {mu}mol/L, P = 0.01). A multivariate analysis showed an independent relationship between the probability of axillary metastasis, elevated THC level (P = 0.01), and tumour size (P = 0.001). The odds ratio with THC {>=} 140 {mu}mol/L was 13.651 (1.781-104.560), whereas that of tumour size with a 1 cm increment was only 1.777 (1.283-2.246). Conclusions: The THC level and the tumour size are independent and preoperative predictors of axillary nodal status; these variables may improve the diagnosis of patients with lymph node metastasis.

  10. Volume based DCE-MRI breast cancer detection with 3D visualization system

    International Nuclear Information System (INIS)

    Chia, F.K.; Sim, K.S.; Chong, S.S.; Tan, S.T.; Ting, H.Y.; Abbas, S.F.; Omar, S.

    2011-01-01

    In this paper, a computer aided design auto probing system is presented to detect breast lesions based on Dynamic contrast enhanced Magnetic resonance imaging (DCE-MRI) images. The system is proposed in order to aid the radiologists and doctors in the interpretation of MRI breast images and enhance the detection accuracy. A series of approaches are presented to enhance the detection accuracy and refine the breast region of interest (Roil) automatically. Besides, a semi-quantitative analysis is used to segment the breast lesions from selected breast Roil and classify the detected tumour is whether benign, suspicious or malignant. The entire breast Roil including the detected tumour will display in 3D. The methodology has been applied on 104 sets of digital imaging and communications in medicine (Dico) breast MRI datasets images. The biopsy results are verified by 2 radiologists from Hospital Malaysia. The experimental results are demonstrated the proposed scheme can precisely identify breast cancer regions with 93% accuracy. (author)

  11. Breast cancer recurrence after reoperation for surgical bleeding

    DEFF Research Database (Denmark)

    Pedersen, Rikke Nørgaard; Bhaskaran, K; Heide-Jørgensen, U

    2017-01-01

    BACKGROUND: Bleeding activates platelets that can bind tumour cells, potentially promoting metastatic growth in patients with cancer. This study investigated whether reoperation for postoperative bleeding is associated with breast cancer recurrence. METHODS: Using the Danish Breast Cancer Group...... database and the Danish National Patient Register (DNPR), a cohort of women with incident stage I-III breast cancer, who underwent breast-conserving surgery or mastectomy during 1996-2008 was identified. Information on reoperation for bleeding within 14 days of the primary surgery was retrieved from...

  12. Role of nuclear receptors in breast cancer stem cells

    Institute of Scientific and Technical Information of China (English)

    Alessio; Papi; Marina; Orlandi

    2016-01-01

    The recapitulation of primary tumour heterogenity and the existence of a minor sub-population of cancer cells,capable of initiating tumour growth in xenografts on serial passages, led to the hypothesis that cancer stem cells(CSCs) exist. CSCs are present in many tumours, among which is breast cancer. Breast CSCs(BCSCs) are likely to sustain the growth of the primary tumour mass, as wellas to be responsible for disease relapse and metastatic spreading. Consequently, BCSCs represent the most significant target for new drugs in breast cancer therapy. Both the hypoxic condition in BCSCs biology and proinflammatory cytokine network has gained increasing importance in the recent past. Breast stromal cells are crucial components of the tumours milieu and are a major source of inflammatory mediators. Recently, the antiinflammatory role of some nuclear receptors ligands has emerged in several diseases, including breast cancer. Therefore, the use of nuclear receptors ligands may be a valid strategy to inhibit BCSCs viability and consequently breast cancer growth and disease relapse.

  13. Correlation between tumour characteristics, SUV measurements, metabolic tumour volume, TLG and textural features assessed with {sup 18}F-FDG PET in a large cohort of oestrogen receptor-positive breast cancer patients

    Energy Technology Data Exchange (ETDEWEB)

    Lemarignier, Charles; Groheux, David [Saint-Louis Hospital, Assistance Publique - Hopitaux de Paris, Department of Nuclear Medicine, Paris (France); University Sorbonne Paris Cite, INSERM/CNRS UMR944/7212, Paris (France); Martineau, Antoine; Vercellino, Laetitia; Merlet, Pascal [Saint-Louis Hospital, Assistance Publique - Hopitaux de Paris, Department of Nuclear Medicine, Paris (France); Teixeira, Luis; Espie, Marc [Saint-Louis Hospital, Breast Diseases Unit, Paris (France); University Sorbonne Paris Cite, INSERM/CNRS UMR944/7212, Paris (France)

    2017-07-15

    The study was designed to evaluate 1) the relationship between PET image textural features (TFs) and SUVs, metabolic tumour volume (MTV), total lesion glycolysis (TLG) and tumour characteristics in a large prospective and homogenous cohort of oestrogen receptor-positive (ER+) breast cancer (BC) patients, and 2) the capability of those parameters to predict response to neoadjuvant chemotherapy (NAC). 171 consecutive patients with large or locally advanced ER+ BC without distant metastases underwent an {sup 18}F-FDG PET examination before NAC. The primary tumour was delineated with an adaptive threshold segmentation method. Parameters of volume, intensity and texture (entropy, homogeneity, contrast and energy) were measured and compared with tumour characteristics determined on pre-treatment breast biopsy (Wilcoxon rank-sum test). The correlation between PET-derived parameters was determined using Spearman's coefficient. The relationship between PET features and pathological findings was determined using the Wilcoxon rank-sum test. Spearman's coefficients between SUV{sub max} and TFs were 0.43, 0.24, -0.43 and -0.15 respectively for entropy, homogeneity, energy and contrast; they were higher between MTV and TFs: 0.99, 0.86, -0.99 and -0.87. All TFs showed a significant association with the histological type (IDC vs. ILC; 0.02 < P < 0.03) but didn't with immunohistochemical characteristics. SUV{sub max} and TLG predicted the pathological response (P = 0.0021 and P = 0.02 respectively); TFs didn't (P: 0.27, 0.19, 0.94, 0.19 respectively for entropy, homogeneity, energy and contrast). The correlation of TFs was poor with SUV parameters and high with MTV. TFs showed a significant association with the histological type. Finally, while SUV{sub max} and TLG were able to predict response to NAC, TFs failed. (orig.)

  14. Staging Investigations in Breast Cancer: Collective Opinion of UK Breast Surgeons

    Directory of Open Access Journals (Sweden)

    N. Chand

    2013-01-01

    Full Text Available Introduction. Certain clinicopathological factors are associated with a higher likelihood of distant metastases in primary breast cancer. However, there remains inconsistency in which patients undergo formal staging for distant metastasis and the most appropriate investigation(s. Aims. To identify UK surgeon preferences and practice with regard to staging investigations for distant metastases. Methods. A survey was disseminated to members of the Association of Breast Surgery by e-mail regarding surgeon/breast unit demographics, use of staging investigations, and local policy on pre/postoperative staging investigations. Several patient scenarios were also presented. Results. 123 of 474 (25.9% recipients completed the survey. Investigations routinely employed for patients diagnosed with early breast cancer included serological/haematological tests (72% respondents, axillary ultrasound (67%, liver ultrasound (2%, chest radiograph (36%, and computed tomography (CT (1%. Three areas contributed to decisions to undertake staging by CT scan: tumour size, axillary nodal status, and plan for chemotherapy. There was widespread variation as to criteria for CT staging based on tumour size and nodal status, as well as the choice of staging investigation for the clinical scenarios presented. Conclusions. There remains variation in the use of staging investigations for distant disease in early breastcancer despite available guidelines.

  15. Tumour cell heterogeneity maintained by cooperating subclones in Wnt-driven mammary cancers.

    Science.gov (United States)

    Cleary, Allison S; Leonard, Travis L; Gestl, Shelley A; Gunther, Edward J

    2014-04-03

    Cancer genome sequencing studies indicate that a single breast cancer typically harbours multiple genetically distinct subclones. As carcinogenesis involves a breakdown in the cell-cell cooperation that normally maintains epithelial tissue architecture, individual subclones within a malignant microenvironment are commonly depicted as self-interested competitors. Alternatively, breast cancer subclones might interact cooperatively to gain a selective growth advantage in some cases. Although interclonal cooperation has been shown to drive tumorigenesis in fruitfly models, definitive evidence for functional cooperation between epithelial tumour cell subclones in mammals is lacking. Here we use mouse models of breast cancer to show that interclonal cooperation can be essential for tumour maintenance. Aberrant expression of the secreted signalling molecule Wnt1 generates mixed-lineage mammary tumours composed of basal and luminal tumour cell subtypes, which purportedly derive from a bipotent malignant progenitor cell residing atop a tumour cell hierarchy. Using somatic Hras mutations as clonal markers, we show that some Wnt tumours indeed conform to a hierarchical configuration, but that others unexpectedly harbour genetically distinct basal Hras mutant and luminal Hras wild-type subclones. Both subclones are required for efficient tumour propagation, which strictly depends on luminally produced Wnt1. When biclonal tumours were challenged with Wnt withdrawal to simulate targeted therapy, analysis of tumour regression and relapse revealed that basal subclones recruit heterologous Wnt-producing cells to restore tumour growth. Alternatively, in the absence of a substitute Wnt source, the original subclones often evolve to rescue Wnt pathway activation and drive relapse, either by restoring cooperation or by switching to a defector strategy. Uncovering similar modes of interclonal cooperation in human cancers may inform efforts aimed at eradicating tumour cell communities.

  16. Clinical Significance of HER-2 Splice Variants in Breast Cancer Progression and Drug Resistance

    Directory of Open Access Journals (Sweden)

    Claire Jackson

    2013-01-01

    Full Text Available Overexpression of human epidermal growth factor receptor (HER-2 occurs in 20–30% of breast cancers and confers survival and proliferative advantages on the tumour cells making HER-2 an ideal therapeutic target for drugs like Herceptin. Continued delineation of tumour biology has identified splice variants of HER-2, with contrasting roles in tumour cell biology. For example, the splice variant 16HER-2 (results from exon 16 skipping increases transformation of cancer cells and is associated with treatment resistance; conversely, Herstatin (results from intron 8 retention and p100 (results from intron 15 retention inhibit tumour cell proliferation. This review focuses on the potential clinical implications of the expression and coexistence of HER-2 splice variants in cancer cells in relation to breast cancer progression and drug resistance. “Individualised” strategies currently guide breast cancer management; in accordance, HER-2 splice variants may prove valuable as future prognostic and predictive factors, as well as potential therapeutic targets.

  17. Genetic bases of the radiosensitivity of breast cancer

    International Nuclear Information System (INIS)

    Delaloge, S.; Marsiglia, H.

    2005-01-01

    Local-regional radiation therapy is one of the major therapeutic means in the management of breast cancer. Three questions however arise from the important advances, achieved in this domain in the past years. The first question concerns the possibilities to identify and overcome the radioresistance of a subset of tumours. The second question is how to recognize women likely to benefit from adjuvant radiation therapy, and therefore to diminish treatment indications in other groups. Finally, the third question is how to identify subjects at high risk for long term injury following breast irradiation, in order to adapt techniques and indications in such populations. The major advances of breast cancer molecular genetics in the past years should provide clinicians with tools to answer these important questions. In this paper, we review the molecular germ line (BRCA1, BRCA2, ATM,...) and somatic (p53, tyrosine kinase receptors, as well as actors of cell cycle, signal transduction, apoptosis, DNA repair...) main bases of breast cancer radiosensitivity. Recent methods of exploration of the genetic background of both the host and the tumours (gene and protein expression profiles) are also reviewed as major tools of breast cancer management in the next few years. (author)

  18. Lack of TIMP-1 tumour cell immunoreactivity predicts effect of adjuvant anthracycline-based chemotherapy in patients (n=647) with primary breast cancer

    DEFF Research Database (Denmark)

    Willemoe, Gro L.; Hertel, Pernille Bræmer; Bartels, Annette

    2009-01-01

    PURPOSE: A number of prospective studies have shown that adjuvant CEF significantly improves disease-free and overall survival as compared to CMF in breast cancer patients. Our aim was to determine whether the benefit of epirubicin versus methotrexate differs according to TIMP-1 tumour cell...

  19. Implementation of TMA and digitalization in routine diagnostics of breast pathology

    DEFF Research Database (Denmark)

    Rossing, Henrik Holm; Talman, Maj-Lis; Laenkholm, Anne-Vibeke

    2012-01-01

    To ensure optimal treatment of breast cancer patients, breast tumours are classified based on clinico-pathological features. As part of this process, routine diagnostics of breast tumours includes histological typing and grading, as well as profiling by use of an immunohistochemistry panel...... of antibodies, probes and in situ hybridization. This will, as a minimum, include assessment of oestrogen receptor (OR) and HER2. The individual preparation and staining of many breast tumours in a large laboratory with this standard panel is thus time consuming and costly. Herein, we show that in breast cancer...... routine diagnostics the use of the tissue microarray technique in combination with digitalization of the stained multi-slides is not only economical, with a considerable cost reduction, but it also enhances standardization of tumour profiling. We demonstrate that 2 mm breast tumour cores correlate...

  20. Nottingham Prognostic Index in Triple-Negative Breast Cancer: a reliable prognostic tool?

    International Nuclear Information System (INIS)

    Albergaria, André; Ricardo, Sara; Milanezi, Fernanda; Carneiro, Vítor; Amendoeira, Isabel; Vieira, Daniella; Cameselle-Teijeiro, Jorge; Schmitt, Fernando

    2011-01-01

    A breast cancer prognostic tool should ideally be applicable to all types of invasive breast lesions. A number of studies have shown histopathological grade to be an independent prognostic factor in breast cancer, adding prognostic power to nodal stage and tumour size. The Nottingham Prognostic Index has been shown to accurately predict patient outcome in stratified groups with a follow-up period of 15 years after primary diagnosis of breast cancer. Clinically, breast tumours that lack the expression of Oestrogen Receptor, Progesterone Receptor and Human Epidermal growth factor Receptor 2 (HER2) are identified as presenting a 'triple-negative' phenotype or as triple-negative breast cancers. These poor outcome tumours represent an easily recognisable prognostic group of breast cancer with aggressive behaviour that currently lack the benefit of available systemic therapy. There are conflicting results on the prevalence of lymph node metastasis at the time of diagnosis in triple-negative breast cancer patients but it is currently accepted that triple-negative breast cancer does not metastasize to axillary nodes and bones as frequently as the non-triple-negative carcinomas, favouring instead, a preferentially haematogenous spread. Hypothetically, this particular tumour dissemination pattern would impair the reliability of using Nottingham Prognostic Index as a tool for triple-negative breast cancer prognostication. The present study tested the effectiveness of the Nottingham Prognostic Index in stratifying breast cancer patients of different subtypes with special emphasis in a triple-negative breast cancer patient subset versus non- triple-negative breast cancer. We demonstrated that besides the fact that TNBC disseminate to axillary lymph nodes as frequently as luminal or HER2 tumours, we also showed that TNBC are larger in size compared with other subtypes and almost all grade 3. Additionally, survival curves demonstrated that these prognostic factors are

  1. Growth of breast cancer recurrences assessed by consecutive MRI

    International Nuclear Information System (INIS)

    Millet, Ingrid; Bouic-Pages, Emmanuelle; Hoa, Denis; Azria, David; Taourel, Patrice

    2011-01-01

    Women with a personal history of breast cancer have a high risk of developing an ipsi- or contralateral recurrence. We aimed to compare the growth rate of primary breast cancer and recurrences in women who had undergone prior breast magnetic resonance imaging (MRI). Three hundred and sixty-two women were diagnosed with breast cancer and had undergone breast MRI at the time of diagnosis in our institution (2005 - 2009). Among them, 37 had at least one prior breast MRI with the lesion being visible but not diagnosed as cancer. A linear regression of tumour volume measured on MRI scans and time data was performed using a generalized logistic model to calculate growth rates. The primary objective was to compare the tumour growth rate of patients with either primary breast cancer (no history of breast cancer) or ipsi- or contralateral recurrences of breast cancer. Twenty women had no history of breast cancer and 17 patients were diagnosed as recurrences (7 and 10 were ipsi- and contralateral, respectively). The tumour growth rate was higher in contralateral recurrences than in ipsilateral recurrences (growth rate [10 -3 days -1 ] 3.56 vs 1.38, p < .001) or primary cancer (3.56 vs 2.09, p = 0.01). Differences in tumour growth were not significant for other patient-, tumour- or treatment-related characteristics. These findings suggest that contralateral breast cancer presents accelerated growth compared to ipsilateral recurrences or primary breast events

  2. Digital breast tomosynthesis (DBT) to characterize MRI-detected additional lesions unidentified at targeted ultrasound in newly diagnosed breast cancer patients

    International Nuclear Information System (INIS)

    Mariscotti, Giovanna; Durando, Manuela; Regini, Elisa; Fornari, Alberto; Fonio, Paolo; Gandini, Giovanni; Houssami, Nehmat; Campanino, Pier Paolo; Bussone, Riccardo; Castellano, Isabella; Sapino, Anna

    2015-01-01

    Preoperative breast magnetic resonance (MR) often generates additional suspicious findings needing further investigations. Targeted breast ultrasound (US) is the standard tool to characterize MR additional lesions. The purpose of this study is to evaluate the potential role of digital breast tomosynthesis (DBT) to characterize MR detected additional findings, unidentified at targeted breast US. This prospective study included women who a) had biopsy-proven, newly diagnosed breast cancers detected at conventional 2D mammography and/or US, referred to breast MR for tumour staging; and b) had DBT if additional MR findings were not detected at targeted ('second look') US. In 520 patients, MR identified 164 (in 114 women, 22 %) additional enhancing lesions. Targeted US identified 114/164 (69.5 %) of these, whereas 50/164 (30.5 %) remained unidentified. DBT identified 32/50 of these cases, increasing the overall characterization of MR detected additional findings to 89.0 % (146/164). Using DBT the identified lesions were significantly more likely to be malignant than benign MR-detected additional lesions (p = 0.04). DBT improves the characterization of additional MR findings not identified at targeted breast US in preoperative breast cancer staging. (orig.)

  3. Digital breast tomosynthesis (DBT) to characterize MRI-detected additional lesions unidentified at targeted ultrasound in newly diagnosed breast cancer patients

    Energy Technology Data Exchange (ETDEWEB)

    Mariscotti, Giovanna; Durando, Manuela; Regini, Elisa; Fornari, Alberto; Fonio, Paolo; Gandini, Giovanni [Breast Imaging Service, Radiology - University of Turin, Department of Diagnostic Imaging and Radiotherapy, A.O.U. Citta della Salute e della Scienza, Torino (Italy); Houssami, Nehmat [University of Sydney, Screening and Test Evaluation Program, School of Public Health, Sydney Medical School, Sydney, NSW (Australia); Campanino, Pier Paolo [Ospedale Koelliker, Breast Imaging Service, Torino (Italy); Bussone, Riccardo [A.O.U. Citta della Salute e della Scienza of Turin, SSCVD Breast Surgery. Department of Surgery, Torino (Italy); Castellano, Isabella; Sapino, Anna [University of Turin, Department of Biomedical Sciences and Human Oncology, A.O.U. Citta della Salute e della Scienza, Torino (Italy)

    2015-09-15

    Preoperative breast magnetic resonance (MR) often generates additional suspicious findings needing further investigations. Targeted breast ultrasound (US) is the standard tool to characterize MR additional lesions. The purpose of this study is to evaluate the potential role of digital breast tomosynthesis (DBT) to characterize MR detected additional findings, unidentified at targeted breast US. This prospective study included women who a) had biopsy-proven, newly diagnosed breast cancers detected at conventional 2D mammography and/or US, referred to breast MR for tumour staging; and b) had DBT if additional MR findings were not detected at targeted ('second look') US. In 520 patients, MR identified 164 (in 114 women, 22 %) additional enhancing lesions. Targeted US identified 114/164 (69.5 %) of these, whereas 50/164 (30.5 %) remained unidentified. DBT identified 32/50 of these cases, increasing the overall characterization of MR detected additional findings to 89.0 % (146/164). Using DBT the identified lesions were significantly more likely to be malignant than benign MR-detected additional lesions (p = 0.04). DBT improves the characterization of additional MR findings not identified at targeted breast US in preoperative breast cancer staging. (orig.)

  4. Tumours associated with medical X-ray therapy exposure in childhood

    International Nuclear Information System (INIS)

    Colman, M.; Kirsch, M.; Creditor, M.

    1978-01-01

    A total of 5166 persons who were exposed to limited field (80-100 cm 2 ) X-ray irradiation to the head, neck and upper chest region during childhood and adolescence have provided an outstanding opportunity for the study of tumour incidence following medical X-ray therapy. More than 3254 subjects have been traced, 3108 have completed questionnaires eliciting information on tumour incidence, and 1539 of these were subjected to a thorough clinical screening procedure that included a thyroid scintigram. The prevalence of thyroid tumours in the 1539 clinically screened subjects and the prevalence of all other tumours in the 3254 subjects traced can therefore be assumed to reflect the risks in the group of irradiated subjects as a whole. Median age at irradiation was 3.5 years, and median radiation dose 790 rads (7.9 Gy). Thyroid tumour was diagnosed in 413 subjects. Of those undergoing surgery (273) 30.3% were found to have thyroid cancer. A total of 366 surgical pathology specimens of the thyroid, including 93 from subjects who were diagnosed at other hospitals, were examined revealing 73 papillary carcinomas, 12 follicular carcinomas and 26 microscopic papillary carcinomas. One hundred and eighty-seven other (non-thyroid) neoplasmas identified included 27 benign and 10 malignant salivary gland tumours, 16 benign and seven malignant tumours of neural origin (brain, spinal cord, cranial and peripheral nerves), 37 skin tumours, 9 lymphomas, 8 gonadal tumours, 45 breast tumours and 28 tumours of miscellaneous sites. The incidence of thyroid tumours, salivary gland tumours and primary brain tumours was considerably in excess of the expected incidence (p values<0.0001), and a radiation dose-effect correlation was observed for thyroid and brain tumours. Gonadal tumours and lymphomas did not occur in excess of the expected incidence

  5. The tumour border on contrast-enhanced spectral mammography and its relation to histological characteristics of invasive breast cancer.

    Science.gov (United States)

    Ambicka, Aleksandra; Luczynska, Elzbieta; Adamczyk, Agnieszka; Harazin-Lechowska, Agnieszka; Sas-Korczynska, Beata; Niemiec, Joanna

    Contrast-enhanced spectral mammography (CESM) is one of the new diagnostic modalities implemented in clinical practice. In the case of these techniques, there are two major issues to be addressed: (1) their diagnostic usefulness, and (2) the relation between parameters assessed using these techniques and well-known diagnostic/prognostic/predictive markers (histological, clinical, and molecular). Therefore, we studied the relationship between the tumour margin assessed on CESM and (1) tumour borders defined on the basis of macroscopic and microscopic examination, (2) pT, (3) pN, and (4) tumour grade in a group of 82 breast cancer patients. Based on CESM, the tumour border was defined as sharp, indistinct or spiculated, whereas in the case of lesions showing weak or medium enhancement on CESM the borders were classified as unspecified. We found a statistically significant relationship between tumour margin on CESM and (1) macroscopic border (a spiculated margin on CESM was found only in carcinomas with an invasive border on histological examination; p = 0.004), (2) pT (p = 0.016), and (3) pN (nodal involvement was observed most frequently in carcinomas with a spiculated or indistinct margin on CESM; p = 0.045). Moreover, in cases with an undefined margin on CESM (cases showing weak or medium enhancement on CESM), both invasive and pushing borders were found on histological examination. The results of our preliminary study suggest that it is possible to assess macroscopic borders of examined lesions on the basis of CESM imaging. This might be useful in planning the extent of surgical excision. On the other hand, the assessment of the tumour margin on CESM might not be precise in cases showing weak enhancement.

  6. Hypoxic enhancement of exosome release by breast cancer cells

    International Nuclear Information System (INIS)

    King, Hamish W; Michael, Michael Z; Gleadle, Jonathan M

    2012-01-01

    Exosomes are nanovesicles secreted by tumour cells which have roles in paracrine signalling during tumour progression, including tumour-stromal interactions, activation of proliferative pathways and bestowing immunosuppression. Hypoxia is an important feature of solid tumours which promotes tumour progression, angiogenesis and metastasis, potentially through exosome-mediated signalling. Breast cancer cell lines were cultured under either moderate (1% O 2 ) or severe (0.1% O 2 ) hypoxia. Exosomes were isolated from conditioned media and quantitated by nanoparticle tracking analysis (NTA) and immunoblotting for the exosomal protein CD63 in order to assess the impact of hypoxia on exosome release. Hypoxic exosome fractions were assayed for miR-210 by real-time reverse transcription polymerase chain reaction and normalised to exogenous and endogenous control genes. Statistical significance was determined using the Student T test with a P value of < 0.05 considered significant. Exposure of three different breast cancer cell lines to moderate (1% O 2 ) and severe (0.1% O 2 ) hypoxia resulted in significant increases in the number of exosomes present in the conditioned media as determined by NTA and CD63 immunoblotting. Activation of hypoxic signalling by dimethyloxalylglycine, a hypoxia-inducible factor (HIF) hydroxylase inhibitor, resulted in significant increase in exosome release. Transfection of cells with HIF-1α siRNA prior to hypoxic exposure prevented the enhancement of exosome release by hypoxia. The hypoxically regulated miR-210 was identified to be present at elevated levels in hypoxic exosome fractions. These data provide evidence that hypoxia promotes the release of exosomes by breast cancer cells, and that this hypoxic response may be mediated by HIF-1α. Given an emerging role for tumour cell-derived exosomes in tumour progression, this has significant implications for understanding the hypoxic tumour phenotype, whereby hypoxic cancer cells may release

  7. The pathology of familial breast cancer: Immunohistochemistry and molecular analysis

    International Nuclear Information System (INIS)

    Osin, Pinchas P; Lakhani, Sunil R

    1999-01-01

    Extensive studies of BRCA1- and BRCA2-associated breast tumours have been carried out in the few years since the identification of these familial breast cancer predisposing genes. The morphological studies suggest that BRCA1 tumours differ from BRCA2 tumours and from sporadic breast cancers. Recent progress in immunohistochemistry and molecular biology techniques has enabled in-depth investigation of molecular pathology of these tumours. Studies to date have investigated issues such as steroid hormone receptor expression, mutation status of tumour suppressor genes TP53 and c-erbB2, and expression profiles of cell cycle proteins p21, p27 and cyclin D 1 . Despite relative paucity of data, strong evidence of unique biological characteristics of BRCA1-associated breast cancer is accumulating. BRCA1-associated tumours appear to show an increased frequency of TP53 mutations, frequent p53 protein stabilization and absence of imunoreactivity for steroid hormone receptors. Further studies of larger number of samples of both BRCA1- and BRCA2-associated tumours are necessary to clarify and confirm these observations

  8. Multidisciplinary team working across different tumour types: analysis of a national survey.

    Science.gov (United States)

    Lamb, B W; Sevdalis, N; Taylor, C; Vincent, C; Green, J S A

    2012-05-01

    Using data from a national survey, this study aimed to address whether the current model for multidisciplinary team (MDT) working is appropriate for all tumour types. Responses to the 2009 National Cancer Action Team national survey were analysed by tumour type. Differences indicate lack of consensus between MDT members in different tumour types. One thousand one hundred and forty-one respondents from breast, gynaecological, colorectal, upper gastrointestinal, urological, head and neck, haematological and lung MDTs were included. One hundred and sixteen of 136 statements demonstrated consensus between respondents in different tumour types. There were no differences regarding the infrastructure for meetings and team governance. Significant consensus was seen for team characteristics, and respondents disagreed regarding certain aspects of meeting organisations and logistics, and patient-centred decision making. Haematology MDT members were outliers in relation to the clinical decision-making process, and lung MDT members disagreed with other tumour types regarding treating patients with advanced disease. This analysis reveals strong consensus between MDT members from different tumour types, while also identifying areas that require a more tailored approach, such as the clinical decision-making process, and preparation for and the organisation of MDT meetings. Policymakers should remain sensitive to the needs of health care teams working in individual tumour types.

  9. Breast cancer staqging using technitium-99m sestamibi and indium-111 pentetreotide single-photon emission tomography

    International Nuclear Information System (INIS)

    Chiti, A.; Agresti, R.; Maffioli, L.S.; Tomasic, G.; Savelli, G.; Crippa, F.; Pilotti, S.; Greco, M.; Bombardieri, E.

    1997-01-01

    We evaluated the clinical usefulness of single-photon emission tomography (SPET) with technetium-99m sestamibi and indium-111 pentetrotide in breast cancer staging. Fifteen patients with clinical and/or mammographic findings suggesting Tl-2N0-l breast cancer were studied. SPET images were acquired 20 min after 99m Tc-sestamibi injection and 4 and 24 h after 111 In-pentetreotide injection. Patients underwent surgery the day after the later 111 In-pentetrotide acquisition. Pathological examination showed 16 tumours in the 15 patients, with one bilateral carcinoma. The mean tumour diamter was 18.7 mm. Metastatic axillary involment was found in 6/16 tumours, with a mean of five metastatic nodes per axillary node involment. Both tracers correctly identified 15/16 primary tumours and five of the six cases of metastatic axillary node involvement. No difference between the tracers was observed in breast cancer staging. 99m Tc-sestamibi seems to the better tracer in terms of physical characteristics, execution time and cost-effectivness. Our data suggest the future possibility of using nuclear medicine imaging to avoid axillary dissection in patiens with Tl breast cancer

  10. MMP-1 expression has an independent prognostic value in breast cancer

    International Nuclear Information System (INIS)

    Boström, Pia; Söderström, Mirva; Vahlberg, Tero; Söderström, Karl-Ove; Roberts, Peter J; Carpén, Olli; Hirsimäki, Pirkko

    2011-01-01

    Breast cancer consists of a variety of tumours, which differ by their morphological features, molecular characteristics and outcome. Well-known prognostic factors, e.g. tumour grade and size, Ki-67, hormone receptor status, HER2 expression, lymph node status and patient age have been traditionally related to prognosis. Although the conventional prognostic markers are reliable in general, better markers to predict the outcome of an individual tumour are needed. Matrix metalloproteinase-1 (MMP-1) expression has been reported to inversely correlate with survival in advanced cancers. In breast cancer MMP-1 is often upregulated, especially in basal-type breast tumours. The purpose of this retrospective study was to analyse MMP-1 expression in breast cancer cells and in cancer associated stromal cells and to correlate the results with traditional prognostic factors including p53 and bcl-2, as well as to patient survival in breast cancer subtypes. Immunohistochemical analysis of MMP-1, ER, PR, Ki-67, HER2, bcl-2, p53 and CK5/6 expression was performed on 125 breast cancers. Statistical analyses were carried out using Kruskal-Wallis and Mann-Whitney -tests. In pairwise comparison Bonferroni-adjustment was applied. Correlations were calculated using Spearman rank-order correlation coefficients. Kaplan-Meier survival analyses were carried out to compare breast cancer-specific survival curves. Factors significantly associated with disease-specific survival in univariate models were included in multivariate stepwise. Positive correlations were found between tumour grade and MMP-1 expression in tumour cells and in stromal cells. P53 positivity significantly correlated with MMP-1 expression in tumour cells, whereas HER2 expression correlated with MMP-1 both in tumour cells and stromal cells. MMP-1 expression in stromal cells showed a significant association with luminal A and luminal B, HER2 overexpressing and triple-negative breast cancer subtypes. The most important finding of

  11. The tumour border on contrast-enhanced spectral mammography and its relation to histological characteristics of invasive breast cancer

    Directory of Open Access Journals (Sweden)

    Aleksandra Ambicka

    2016-11-01

    Full Text Available Contrast-enhanced spectral mammography (CESM is one of the new diagnostic modalities implemented in clinical practice. In the case of these techniques, there are two major issues to be addressed: (1 their diagnostic usefulness, and (2 the relation between parameters assessed using these techniques and well-known diagnostic/prognostic/predictive markers (histological, clinical, and molecular. Therefore, we studied the relationship between the tumour margin assessed on CESM and (1 tumour borders defined on the basis of macroscopic and microscopic examination, (2 pT, (3 pN, and (4 tumour grade in a group of 82 breast cancer patients. Based on CESM, the tumour border was defined as sharp, indistinct or spiculated, whereas in the case of lesions showing weak or medium enhancement on CESM the borders were classified as unspecified. We found a statistically significant relationship between tumour margin on CESM and (1 macroscopic border (a spiculated margin on CESM was found only in carcinomas with an invasive border on histological examination; p = 0.004, (2 pT (p = 0.016, and (3 pN (nodal involvement was observed most frequently in carcinomas with a spiculated or indistinct margin on CESM; p = 0.045. Moreover, in cases with an undefined margin on CESM (cases showing weak or medium enhancement on CESM, both invasive and pushing borders were found on histological examination. The results of our preliminary study suggest that it is possible to assess macroscopic borders of examined lesions on the basis of CESM imaging. This might be useful in planning the extent of surgical excision. On the other hand, the assessment of the tumour margin on CESM might not be precise in cases showing weak enhancement.

  12. Anti-tumour therapeutic efficacy of OX40L in murine tumour model.

    Science.gov (United States)

    Ali, Selman A; Ahmad, Murrium; Lynam, June; McLean, Cornelia S; Entwisle, Claire; Loudon, Peter; Choolun, Esther; McArdle, Stephanie E B; Li, Geng; Mian, Shahid; Rees, Robert C

    2004-09-09

    OX40 ligand (OX40L), a member of TNF superfamily, is a co-stimulatory molecule involved in T cell activation. Systemic administration of mOX40L fusion protein significantly inhibited the growth of experimental lung metastasis and subcutaneous (s.c.) established colon (CT26) and breast (4T1) carcinomas. Vaccination with OX40L was significantly enhanced by combination treatment with intra-tumour injection of a disabled infectious single cycle-herpes simplex virus (DISC-HSV) vector encoding murine granulocyte macrophage-colony stimulating factor (mGM-CSF). Tumour rejection in response to OX40L therapy required functional CD4+ and CD8+ T cells and correlated with splenocyte cytotoxic T lymphocytes (CTLs) activity against the AH-1 gp70 peptide of the tumour associated antigen expressed by CT26 cells. These results demonstrate the potential role of the OX40L in cancer immunotherapy.

  13. The Efficacy of Trastuzumab in Animal Models of Breast Cancer: A Systematic Review and Meta-Analysis.

    Directory of Open Access Journals (Sweden)

    Jiarong Chen

    Full Text Available Breast cancer is the most frequent cancers and is the second leading cause of cancer death among women. Trastuzumab is an effective treatment, the first monoclonal antibody directed against the human epidermal growth factor receptor 2 (HER2. To inform the development of other effective treatments we report summary estimates of efficacy of trastuzumab on survival and tumour volume in animal models of breast cancer.We searched PubMed and EMBASE systematically to identify publications testing trastuzumab in animal models of breast cancer. Data describing tumour volume, median survival and animal features were extracted and we assessed quality using a 12-item checklist. We analysed the impact of study design and quality and evidence for publication bias.We included data from 83 studies reporting 169 experiments using 2076 mice. Trastuzumab treatment caused a substantial reduction in tumour growth, with tumours in treated animals growing to 32.6% of the volume of tumours in control animals (95%CI 27.8%-38.2%. Median survival was prolonged by a factor of 1.45 (1.30-1.62. Many study design and quality features accounted for between-study heterogeneity and we found evidence suggesting publication bias.We have found trastuzumab to be effective in animal breast cancer models across a range of experimental circumstances. However the presence of publication bias and a low prevalence of measures to reduce bias provide a focus for future improvements in preclinical breast cancer research.

  14. Cytological Criteria to Distinguish Phyllodes Tumour of the Breast from Fibroadenoma.

    Science.gov (United States)

    Maritz, Robert M; Michelow, Pamela M

    2017-01-01

    To determine whether there are significant differences between fibroadenomas and phyllodes tumours with regard to selected cytomorphological features. A 10-year retrospective review was performed of patients who underwent excision of a fibroadenoma or phyllodes tumour and in whom a preoperative fine-needle aspiration was performed. The following cytological criteria were assessed: number of stromal and epithelial fragments, stromal-to-epithelial ratio, stromal cellularity, stromal borders, stromal atypia, and proportion of background wavy spindled cells. Patient age, tumour laterality, and tumour size were recorded. Fifty fibroadenomas and 17 phyllodes tumours were included. Compared to phyllodes tumours, fibroadenomas had a larger number of epithelial fragments, a smaller number of stromal fragments, and a lower stromal-to-epithelial ratio. The stroma tended to be less cellular and less atypical compared to phyllodes tumours and the background cellular population contained fewer spindled cells. Fibroadenomas and phyllodes tumours differ with regard to various cytological features, aiding in their distinction on fine-needle aspiration biopsy. © 2017 S. Karger AG, Basel.

  15. lmmunohistochemical study of effect of ionizing radiation on human malignant tumours

    International Nuclear Information System (INIS)

    Adomaitiene, D. I.; Aleknavicius, E.; Valuckas, K. and others

    2000-01-01

    Cell proliferation-associated tumour markers are considered to have a valuable clinical significance. The current study was designed to investigate changes in immunohistochemical (IH) expression of proliferating cell nuclear antigen PCNA in human malignant tumour tissue samples obtained before and after preoperative radiotherapy. Tumour tissue samples were obtained from 26 patients with rectal carcinoma, from 22 patients with carcinoma corporis uteri and from 82 patients with breast cancer. Tumour samples were processed for IH examination by using monoclonal antibodies (MoAbs) PC10 against PCNA. IH analysis of histological specimens of carcinoma corporis uteri and rectal carcinoma obtained before and after preoperative radiotherapy has revealed heterogeneity of biological response to irradiation. The great majority of tumour specimens after irradiation showed a high PCNA expression level in cell population. Only minority of tumour specimens (15-20%) exhibited reduced immunoreactivity with MoAbs PC10. PCNA positivity rate in breast cancer specimens obtained during surgery from 55 patients after preoperative radiotherapy in comparison to biomarker expression pattern in tumour specimens from 27 unirradiated patients (control group) was found to be tended to decrease. These in vivo findings are discussed in terms of radiation-induced cell death, followed after proliferation, and PCNA role in DNA repair. (author)

  16. Breast metastases from rectal carcinoma

    Institute of Scientific and Technical Information of China (English)

    LI Jia; FANG Yu; LI Ang; LI Fei

    2011-01-01

    Metastases to the breast from extramammary neoplasms are very rare, constituting 2.7% of all malignant breast tumours. The most common primary tumor metastatic to the breast is primary breast cancer. Rectal cancer metastasizing to the breast is extremely rare. We report a case of aggressive rectal carcinoma with metastasis to the breast.

  17. Role of endocrine disrupting chemicals on the tissue levels of AhR and sex steroid receptors in breast tumours

    Directory of Open Access Journals (Sweden)

    Sepideh Arbabi Bidgoli

    2016-09-01

    Full Text Available Breast cancer affects Iranian women at least one decade younger than their counterparts in other countries and the incidence of breast fibroadenoma is growing in the last two decades in Tehran. This study aimed to compare the AhR levels in premenopausal breast cancer and breast fibroadnemo with appropriate normal groups. Possible associations of AhR with lifestyle and reproductive risk factors and other fundamental genes of breast cancer and reproductive disorders were the other major goals of present study. To conduct the comparisons all possible reproductive, environmental and lifestyle risk factors of mentioned diseases were recorded in 100 breast cancer, 100 breast fibroadenoma and compared with 400 women in normal group from 2009 to 2011. AhR overexpression in epithelial cells of premenopausal patients emphasized the susceptibility of these cells to environmental induced reproductive disorders. The AhR overexpression was contributed to ER-/PgR- immunophenotype in malignant tissues. Weight gain (after 18 and after pregnancy, long term (>5yrs OCP consumption, smoking, severe stress ,history of ovarian cysts, hormonal deregulations, living near PAHs producing sources, were correlated with increased risk of breast cancer and reproductive disorders and were correlated with elevated tissue levels of AhR. It seems that increased risk of breast cancer and other reproductive tumours in Tehran may be the result of exposure to environmental endocrine disruptors. Long term exposure to environmental estrogens can increase the tissue levels of AhR and deregulate the expression pattern of sex steroid receptors and other genes in target tissues.

  18. Tumour bed delineation for partial breast/breast boost radiotherapy: What is the optimal number of implanted markers?

    International Nuclear Information System (INIS)

    Kirby, Anna NM.; Jena, Rajesh; Harris, Emma J.; Evans, Phil M.; Crowley, Clare; Gregory, Deborah L.; Coles, Charlotte E.

    2013-01-01

    Purpose: International consensus has not been reached regarding the optimal number of implanted tumour bed (TB) markers for partial breast/breast boost radiotherapy target volume delineation. Four common methods are: insertion of 6 clips (4 radial, 1 deep and 1 superficial), 5 clips (4 radial and 1 deep), 1 clip at the chest wall, and no clips. We compared TB volumes delineated using 6, 5, 1 and 0 clips in women who have undergone wide-local excision (WLE) of breast cancer (BC) with full-thickness closure of the excision cavity, in order to determine the additional margin required for breast boost or partial breast irradiation (PBI) when fewer than 6 clips are used. Methods: Ten patients with invasive ductal BC who had undergone WLE followed by implantation of six fiducial markers (titanium clips) each underwent CT imaging for radiotherapy planning purposes. Retrospective processing of the DICOM image datasets was performed to remove markers and associated imaging artefacts, using an in-house software algorithm. Four observers outlined TB volumes on four different datasets for each case: (1) all markers present (CT 6M ); (2) the superficial marker removed (CT 5M ); (3) all but the chest wall marker removed (CT CW ); (4) all markers removed (CT 0M ). For each observer, the additional margin required around each of TB 0M , TB CW , and TB 5M in order to encompass TB 6M was calculated. The conformity level index (CLI) and differences in centre-of-mass (COM) between observers were quantified for CT 0M , CT CW , CT 5M , CT 6M . Results: The overall median additional margins required to encompass TB 6M were 8 mm (range 0–28 mm) for TB 0M , 5 mm (range 1–13 mm) for TB CW , and 2 mm (range 0–7 mm) for TB 5M . CLI were higher for TB volumes delineated using CT 6M (0.31) CT 5M (0.32) than for CT CW (0.19) and CT 0M (0.15). Conclusions: In women who have undergone WLE of breast cancer with full-thickness closure of the excision cavity and who are proceeding to PBI or

  19. Identifying Breast Cancer Oncogenes

    Science.gov (United States)

    2010-10-01

    tyrosine kinases with an SH3, SH2 and catalytic domain, it lacks a native myristylation signal shared by most members of this class [14], [38]. The...therapeutics and consequently, improve clinical outcomes. We aim to identify novel drivers of breast oncogenesis. We hypothesize that a kinase gain-of...human mammary epithelial cells. A pBabe-Puro-Myr-Flag kinase open reading frame (ORF) library was screened in immortalized human mammary epithelial

  20. Comparison of fluorine-18 fluorodeoxyglucose positron emission tomography and technetium-99m methoxyisobutylisonitrile scintimammography in the detection of breast tumours

    Energy Technology Data Exchange (ETDEWEB)

    Palmedo, H.; Bender, H.; Gruenwald, F.; Zamora, P.; Biersack, H.J. [Department of Nuclear Medicine, University of Bonn (Germany); Mallmann, P.; Krebs, D. [Department of Gynecology and Obstetrics, University of Bonn (Germany)

    1997-09-01

    The aim of this study was to compare, in breast cancer patients, the diagnostic accuracy of positron emission tomography (PET) using fluorine-18 fluorodeoxyglucose (FDG) and scintimammography (SMM) using technetium-99m methoxyisobutylisonitrile (MIBI). A total of 20 patients (40 breasts with 22 lesions) were evaluated serially with MIBI and, on the following day, with FDG. For SMM, planar and single-photon emission tomography imaging in the prone position was performed starting at 10 min following the injection of MIBI (740 MBq). For PET, scans were acquired 45-60 min after the injection of FDG (370 MBq) and attentuation correction was performed following transmission scans. Results from SMM and PET were subsequently compared with the histopathology results. True-positive results were obtained in 12/13 primary breast cancers (mean diameter=29 mm, range 8-53 mm) with both FDG and MIBI. False-negative results were obtained in two local recurrences (diameter <9 mm) with both FDG and MIBI. In benign disease, FDG and MIBI did not localize three fibrocystic lesions, two fibroadenomas and one inflammatory lesion (true-negative), but both localized one fibroadenoma (false-positive). Collectively, the results demonstrate a sensitivity of 92%, and a specificity of 86%, for primary breast cancer regardless of whether FDG or MIBI was used. In contrast to MIBI scintigraphy, FDG PET scored the axillae correctly as either positive (metastatic disease) or negative (no axillary disease) in all 12 patients. The tumour/non-tumour ratio for MIBI was 1.97 (range 1.43-3.1). The mean standard uptake value (SUV) for FDG uptake was 2.57 (range 0.3-6.2). The diagnostic accuracy of SMM was equivalent to that of FDG PET for the detection of primary breast cancer. For the detection of in situ lymph node metastases of the axilla, FDG seems to be more sensitive than {sup 99m}Tc-MIBI. (orig.). With 4 figs., 2 tabs.

  1. Breast cancer recurrence after reoperation for surgical bleeding

    DEFF Research Database (Denmark)

    Pedersen, Rikke Nørgaard; Bhaskaran, K; Heide-Jørgensen, U

    2017-01-01

    BACKGROUND: Bleeding activates platelets that can bind tumour cells, potentially promoting metastatic growth in patients with cancer. This study investigated whether reoperation for postoperative bleeding is associated with breast cancer recurrence. METHODS: Using the Danish Breast Cancer Group...... database and the Danish National Patient Register (DNPR), a cohort of women with incident stage I-III breast cancer, who underwent breast-conserving surgery or mastectomy during 1996-2008 was identified. Information on reoperation for bleeding within 14 days of the primary surgery was retrieved from.......i. 0·89 to 1·26). The estimates did not vary by site of breast cancer recurrence. CONCLUSION: In this large cohort study, there was no evidence of an association between reoperation for bleeding and breast cancer recurrence....

  2. The Breast Cancer to Bone (B2B) Metastases Research Program: a multi-disciplinary investigation of bone metastases from breast cancer.

    Science.gov (United States)

    Brockton, Nigel T; Gill, Stephanie J; Laborge, Stephanie L; Paterson, Alexander H G; Cook, Linda S; Vogel, Hans J; Shemanko, Carrie S; Hanley, David A; Magliocco, Anthony M; Friedenreich, Christine M

    2015-07-10

    Bone is the most common site of breast cancer distant metastasis, affecting 50-70 % of patients who develop metastatic disease. Despite decades of informative research, the effective prevention, prediction and treatment of these lesions remains elusive. The Breast Cancer to Bone (B2B) Metastases Research Program consists of a prospective cohort of incident breast cancer patients and four sub-projects that are investigating priority areas in breast cancer bone metastases. These include the impact of lifestyle factors and inflammation on risk of bone metastases, the gene expression features of the primary tumour, the potential role for metabolomics in early detection of bone metastatic disease and the signalling pathways that drive the metastatic lesions in the bone. The B2B Research Program is enrolling a prospective cohort of 600 newly diagnosed, incident, stage I-IIIc breast cancer survivors in Alberta, Canada over a five year period. At baseline, pre-treatment/surgery blood samples are collected and detailed epidemiologic data is collected by in-person interview and self-administered questionnaires. Additional self-administered questionnaires and blood samples are completed at specified follow-up intervals (24, 48 and 72 months). Vital status is obtained prior to each follow-up through record linkages with the Alberta Cancer Registry. Recurrences are identified through medical chart abstractions. Each of the four projects applies specific methods and analyses to assess the impact of serum vitamin D and cytokine concentrations, tumour transcript and protein expression, serum metabolomic profiles and in vitro cell signalling on breast cancer bone metastases. The B2B Research Program will address key issues in breast cancer bone metastases including the association between lifestyle factors (particularly a comprehensive assessment of vitamin D status) inflammation and bone metastases, the significance or primary tumour gene expression in tissue tropism, the

  3. The Breast Cancer to Bone (B2B) Metastases Research Program: a multi-disciplinary investigation of bone metastases from breast cancer

    International Nuclear Information System (INIS)

    Brockton, Nigel T.; Gill, Stephanie J.; Laborge, Stephanie L.; Paterson, Alexander H. G.; Cook, Linda S.; Vogel, Hans J.; Shemanko, Carrie S.; Hanley, David A.; Magliocco, Anthony M.; Friedenreich, Christine M.

    2015-01-01

    Bone is the most common site of breast cancer distant metastasis, affecting 50–70 % of patients who develop metastatic disease. Despite decades of informative research, the effective prevention, prediction and treatment of these lesions remains elusive. The Breast Cancer to Bone (B2B) Metastases Research Program consists of a prospective cohort of incident breast cancer patients and four sub-projects that are investigating priority areas in breast cancer bone metastases. These include the impact of lifestyle factors and inflammation on risk of bone metastases, the gene expression features of the primary tumour, the potential role for metabolomics in early detection of bone metastatic disease and the signalling pathways that drive the metastatic lesions in the bone. The B2B Research Program is enrolling a prospective cohort of 600 newly diagnosed, incident, stage I-IIIc breast cancer survivors in Alberta, Canada over a five year period. At baseline, pre-treatment/surgery blood samples are collected and detailed epidemiologic data is collected by in-person interview and self-administered questionnaires. Additional self-administered questionnaires and blood samples are completed at specified follow-up intervals (24, 48 and 72 months). Vital status is obtained prior to each follow-up through record linkages with the Alberta Cancer Registry. Recurrences are identified through medical chart abstractions. Each of the four projects applies specific methods and analyses to assess the impact of serum vitamin D and cytokine concentrations, tumour transcript and protein expression, serum metabolomic profiles and in vitro cell signalling on breast cancer bone metastases. The B2B Research Program will address key issues in breast cancer bone metastases including the association between lifestyle factors (particularly a comprehensive assessment of vitamin D status) inflammation and bone metastases, the significance or primary tumour gene expression in tissue tropism, the

  4. Implementation of TMA and digitalization in routine diagnostics of breast pathology.

    Science.gov (United States)

    Rossing, Henrik Holm; Talman, Maj-Lis Møller; Laenkholm, Anne-Vibeke; Wielenga, Vera Timmermans

    2012-04-01

    To ensure optimal treatment of breast cancer patients, breast tumours are classified based on clinico-pathological features. As part of this process, routine diagnostics of breast tumours includes histological typing and grading, as well as profiling by use of an immunohistochemistry panel of antibodies, probes and in situ hybridization. This will, as a minimum, include assessment of oestrogen receptor (OR) and HER2. The individual preparation and staining of many breast tumours in a large laboratory with this standard panel is thus time consuming and costly. Herein, we show that in breast cancer routine diagnostics the use of the tissue microarray technique in combination with digitalization of the stained multi-slides is not only economical, with a considerable cost reduction, but it also enhances standardization of tumour profiling. We demonstrate that 2 mm breast tumour cores correlate with the corresponding tumour on whole mount slides, regarding staining/hybridizing results with the biomarkers in our panel consisting of human epidermal growth factor receptor 2, OR and Topiomerase IIa. Furthermore, we show that simultaneous staining/hybridizing of multiple breast tumour specimens reduces variation of staining/hybridizing quality, hereby increasing reliability of interpretation. By scanning and digitalization of the stained and hybridized multi-slides, we could optimize documentation and filing of the results. Our work is an example of translational research by implementing a tool in daily diagnostics originally developed for high throughput analyses in the search for prognostic and predictive markers in targeted medicine. © 2012 The Authors APMIS © 2012 APMIS.

  5. Stromal cell derived factor-1: its influence on invasiveness and migration of breast cancer cells in vitro, and its association with prognosis and survival in human breast cancer

    International Nuclear Information System (INIS)

    Kang, Hua; Watkins, Gareth; Parr, Christian; Douglas-Jones, Anthony; Mansel, Robert E; Jiang, Wen G

    2005-01-01

    Stromal cell-derived factor (SDF)-1 (CXC chemokine ligand-12) is a member of the CXC subfamily of chemokines, which, through its cognate receptor (CXC chemokine receptor [CXCR]4), plays an important role in chemotaxis of cancer cells and in tumour metastasis. We conducted the present study to evaluate the effect of SDF-1 on the invasiveness and migration of breast cancer cells, and we analyzed the expression of SDF-1 and its relation to clinicopathological features and clinical outcomes in human breast cancer. Expression of SDF-1 mRNA in breast cancer, endothelial (HECV) and fibroblast (MRC5) cell lines and in human breast tissues were studied using RT-PCR. MDA-MB-231 cells were transfected with a SDF-1 expression vector, and their invasiveness and migration was tested in vitro. In addition, the expression of SDF-1 was investigated using immunohistochemistry and quantitative RT-PCR in samples of normal human mammary tissue (n = 32) and mammary tumour (n = 120). SDF-1 expression was identified in MRC5, MDA-MB-435s and MDA-MB-436 cell lines, but CXCR4 expression was detected in all cell lines and breast tissues. An autocrine loop was created following transfection of MDA-MB-231 (which was CXCR4 positive and SDF-1 negative) with a mammalian expression cassette encoding SDF-1 (MDA-MB-231SDF1 +/+ ) or with control plasmid pcDNA4/GFP (MDA-MB-231 +/- ). MDA-MB-231SDF1 +/+ cells exhibited significantly greater invasion and migration potential (in transfected cells versus in wild type and empty MDA-MB-231 +/- ; P < 0.01). In mammary tissues SDF-1 staining was primarily seen in stromal cells and weakly in mammary epithelial cells. Significantly higher levels of SDF-1 were seen in node-positive than in node-negative tumours (P = 0.05), in tumours that metastasized (P = 0.05), and tumours from patients who died (P = 0.03) than in tumours from patients who were disease free. It was most notable that levels of SDF-1 correlated significantly with overall survival (P = 0.001) and

  6. Proteomic maps of breast cancer subtypes

    DEFF Research Database (Denmark)

    Tyanova, Stefka; Albrechtsen, Reidar; Kronqvist, Pauliina

    2016-01-01

    Systems-wide profiling of breast cancer has almost always entailed RNA and DNA analysis by microarray and sequencing techniques. Marked developments in proteomic technologies now enable very deep profiling of clinical samples, with high identification and quantification accuracy. We analysed 40...... oestrogen receptor positive (luminal), Her2 positive and triple negative breast tumours and reached a quantitative depth of >10,000 proteins. These proteomic profiles identified functional differences between breast cancer subtypes, related to energy metabolism, cell growth, mRNA translation and cell......-cell communication. Furthermore, we derived a signature of 19 proteins, which differ between the breast cancer subtypes, through support vector machine (SVM)-based classification and feature selection. Remarkably, only three proteins of the signature were associated with gene copy number variations and eleven were...

  7. Association analysis identifies 65 new breast cancer risk loci

    OpenAIRE

    Michailidou, Kyriaki; Lindström, Sara; Dennis, Joe; Beesley, Jonathan; Hui, Shirley; Kar, Siddhartha; Lemaçon, Audrey; Soucy, Penny; Glubb, Dylan; Rostamianfar, Asha; Bolla, Manjeet K; Wang, Qin; Tyrer, Jonathan; Dicks, Ed; Lee, Andrew

    2017-01-01

    Breast cancer risk is influenced by rare coding variants in susceptibility genes, such as BRCA1, and many common, mostly non-coding variants. However, much of the genetic contribution to breast cancer risk remains unknown. Here we report the results of a genome-wide association study of breast cancer in 122,977 cases and 105,974 controls of European ancestry and 14,068 cases and 13,104 controls of East Asian ancestry. We identified 65 new loci that are associated with overall breast cancer ri...

  8. Contralateral breast cancer: incidence according to ductal or lobular phenotype of the primary

    International Nuclear Information System (INIS)

    Langlands, F.; White, J.; Kearins, O.; Cheung, S.; Burns, R.; Horgan, K.; Sharma, N.; Dodwell, D.

    2016-01-01

    Aim: To identify differences in the incidence of contralateral breast cancer between patients with a primary tumour diagnosis of invasive ductal carcinoma (IDC) and those with a diagnosis of invasive lobular carcinoma (ILC). Materials and methods: Data from two large cancer registries (registry A & B) the Northern and Yorkshire Cancer Registry Information Service (NYCRIS) and the West Midlands Cancer Intelligence Unit (WMCIU) from 1998–2003 for all cases of invasive breast cancer of either pure ductal or pure lobular reported histology were obtained. The invasive status of the contralateral tumour diagnosis and tumour morphology was collected. Chi-square tests were undertaken to examine the differences in contralateral rates for both registries and univariate analysis to ascertain which predictors affected contralateral breast cancer risk for registry A the WMCIU cases. Results: A total of 38,132 patients were studied, 32,735 patients with IDC and 5397 (14.2%) patients with ILC over the 6-year period. There was no significant difference between the occurrence and time to occurrence of contralateral breast cancer according to original cancer histology, 901 (2.8%) patients with IDC versus 166 (3.1%) patients with ILC (p=0.169). The analysis of registry A cases showed no association between original histology (ductal versus lobular), age at diagnosis, tumour grade, use of radiotherapy for the primary cancer or use of systemic therapy (chemotherapy and/or endocrine therapy), and development of a contralateral breast cancer. Conclusion: There is no apparent increase in risk of developing a contralateral breast cancer according to the primary cancer histology either IDC or ILC. Standard mammographic follow-up does not need to take account of original tumour pathology. Increased intervention or post-treatment surveillance for the contralateral breast is not indicated in the context of ILC. The role of MRI should be restricted to those patients with ILC who are planning

  9. Prognostic value of Ki67 analysed by cytology or histology in primary breast cancer.

    Science.gov (United States)

    Robertson, Stephanie; Stålhammar, Gustav; Darai-Ramqvist, Eva; Rantalainen, Mattias; Tobin, Nicholas P; Bergh, Jonas; Hartman, Johan

    2018-03-27

    The accuracy of biomarker assessment in breast pathology is vital for therapy decisions. The therapy predictive and prognostic biomarkers oestrogen receptor (ER), progesterone receptor, HER2 and Ki67 may act as surrogates to gene expression profiling of breast cancer. The aims of this study were to investigate the concordance of consecutive biomarker assessment by immunocytochemistry on preoperative fine-needle aspiration cytology versus immunohistochemistry (IHC) on the corresponding resected breast tumours. Further, to investigate the concordance with molecular subtype and correlation to stage and outcome. Two retrospective cohorts comprising 385 breast tumours with clinicopathological data including gene expression-based subtype and up to 10-year overall survival data were evaluated. In both cohorts, we identified a substantial variation in Ki67 index between cytology and histology and a switch between low and high proliferation within the same tumour in 121/360 cases. ER evaluations were discordant in only 1.5% of the tumours. From cohort 2, gene expression data with PAM50 subtype were used to correlate surrogate subtypes. IHC-based surrogate classification could identify the correct molecular subtype in 60% and 64% of patients by cytology (n=63) and surgical resections (n=73), respectively. Furthermore, high Ki67 in surgical resections but not in cytology was associated with poor overall survival and higher probability for axillary lymph node metastasis. This study shows considerable differences in the prognostic value of Ki67 but not ER in breast cancer depending on the diagnostic method. Furthermore, our findings show that both methods are insufficient in predicting true molecular subtypes. © Article author(s) (or their employer(s) unless otherwise stated in the text of the article) 2018. All rights reserved. No commercial use is permitted unless otherwise expressly granted.

  10. Comparing oncoplastic breast conserving surgery with mastectomy and immediate breast reconstruction: Case-matched patient reported outcomes.

    Science.gov (United States)

    Kelsall, Jennett E; McCulley, Stephen J; Brock, Lisa; Akerlund, Malin T E; Macmillan, R Douglas

    2017-10-01

    Oncoplastic breast conserving surgery (OBCS) allows women who may otherwise have mastectomy and immediate reconstruction (MxIR) the choice to conserve their breast yet avoid deformity. We compared the outcome of these options. Two cohorts meeting study criteria were identified from prospectively audited series of women undergoing OBCS or MxIR. After case matching for age, tumour size and date of surgery, stratification by breast size and controlling for radiotherapy; body image scale (BIS) scores of psychosocial function and patient reported outcome measures (PROMs) for breast appearance and return to function were analysed. A total of 567 women (286 treated by OBCS and 281 by MxIR) fulfilled inclusion criteria. Demographics were similar between the two unmatched cohorts, except for radiotherapy, age and tumour size (all p < 0.001). Overall, BIS score (p = 0.002), self-rated breast appearance, return to work and function (all p < 0.001) significantly favoured OBCS. Case-matched women with larger breasts treated by OBCS reported better BIS scores (mean 3.30 vs. 5.37, p = 0.011) and self-rated breast appearance score (p < 0.001) than MxIR, whereas no significant difference was observed for smaller breasts. BIS and appearance favoured OBCS, regardless of whether radiotherapy would have been avoided if treated by MxIR. OBCS offers suitable women the option to avoid MxIR while providing faster recovery. Better psychosocial and self-rated satisfaction with breast appearance is achieved for OBCS in all groups, regardless of the need for radiotherapy, apart from those women with smaller breasts for whom the results are comparable. Copyright © 2017 British Association of Plastic, Reconstructive and Aesthetic Surgeons. Published by Elsevier Ltd. All rights reserved.

  11. Breast Density and Benign Breast Disease: Risk Assessment to Identify Women at High Risk of Breast Cancer.

    Science.gov (United States)

    Tice, Jeffrey A; Miglioretti, Diana L; Li, Chin-Shang; Vachon, Celine M; Gard, Charlotte C; Kerlikowske, Karla

    2015-10-01

    Women with proliferative breast lesions are candidates for primary prevention, but few risk models incorporate benign findings to assess breast cancer risk. We incorporated benign breast disease (BBD) diagnoses into the Breast Cancer Surveillance Consortium (BCSC) risk model, the only breast cancer risk assessment tool that uses breast density. We developed and validated a competing-risk model using 2000 to 2010 SEER data for breast cancer incidence and 2010 vital statistics to adjust for the competing risk of death. We used Cox proportional hazards regression to estimate the relative hazards for age, race/ethnicity, family history of breast cancer, history of breast biopsy, BBD diagnoses, and breast density in the BCSC. We included 1,135,977 women age 35 to 74 years undergoing mammography with no history of breast cancer; 17% of the women had a prior breast biopsy. During a mean follow-up of 6.9 years, 17,908 women were diagnosed with invasive breast cancer. The BCSC BBD model slightly overpredicted risk (expected-to-observed ratio, 1.04; 95% CI, 1.03 to 1.06) and had modest discriminatory accuracy (area under the receiver operator characteristic curve, 0.665). Among women with proliferative findings, adding BBD to the model increased the proportion of women with an estimated 5-year risk of 3% or higher from 9.3% to 27.8% (P<.001). The BCSC BBD model accurately estimates women's risk for breast cancer using breast density and BBD diagnoses. Greater numbers of high-risk women eligible for primary prevention after BBD diagnosis are identified using the BCSC BBD model. © 2015 by American Society of Clinical Oncology.

  12. Loss of heterozygosity on the X chromosome in human breast cancer.

    Science.gov (United States)

    Loupart, M L; Adams, S; Armour, J A; Walker, R; Brammar, W; Varley, J

    1995-08-01

    The analysis of loss of heterozygosity (LOH) in tumours can be a powerful tool for mapping the sites of tumour suppressor genes in the human genome. A panel of breast cancer patients was assembled as pairs of tumour and lymphocyte DNA samples and LOH studies carried out by Southern hybridisation with polymorphic loci mapping to the X chromosome with appropriate controls. Deletion mapping revealed a high frequency of small regionalised deletions, defining at least three independent regions, one of which is particularly well mapped to a 500 kb stretch of DNA in the distal portion of the pseudoautosomal region of Xp. A second region has been identified within the pseudoautosomal region close to the pseudoautosomal boundary, and there is a third discrete site of loss on distal Xq. Perturbations of sequences at these regions represent independent events in a number of patients. This study represents the first detailed analysis of LOH on the X chromosome in human breast tumours, the results of which indicate that at least three regions of this chromosome are involved in the disease.

  13. In situ identification of CD44+/CD24- cancer cells in primary human breast carcinomas.

    Directory of Open Access Journals (Sweden)

    Giuseppe Perrone

    Full Text Available Breast cancer cells with the CD44+/CD24- phenotype have been reported to be tumourigenic due to their enhanced capacity for cancer development and their self-renewal potential. The identification of human tumourigenic breast cancer cells in surgical samples has recently received increased attention due to the implications for prognosis and treatment, although limitations exist in the interpretation of these studies. To better identify the CD44+/CD24- cells in routine surgical specimens, 56 primary breast carcinoma cases were analysed by immunofluorescence and confocal microscopy, and the results were compared using flow cytometry analysis to correlate the amount and distribution of the CD44+/CD24- population with clinicopathological features. Using these methods, we showed that the breast carcinoma cells displayed four distinct sub-populations based on the expression pattern of CD44 and CD24. The CD44+/CD24- cells were found in 91% of breast tumours and constituted an average of 6.12% (range, 0.11%-21.23% of the tumour. A strong correlation was found between the percentage of CD44+/CD24- cells in primary tumours and distant metastasis development (p = 0.0001; in addition, there was an inverse significant association with ER and PGR status (p = 0.002 and p = 0.001, respectively. No relationship was evident with tumour size (T and regional lymph node (N status, differentiation grade, proliferative index or HER2 status. In a multivariate analysis, the percentage of CD44+/CD24- cancer cells was an independent factor related to metastasis development (p = 0.004. Our results indicate that confocal analysis of fluorescence-labelled breast cancer samples obtained at surgery is a reliable method to identify the CD44+/CD24- tumourigenic cell population, allowing for the stratification of breast cancer patients into two groups with substantially different relapse rates on the basis of CD44+/CD24- cell percentage.

  14. Breast cancer epidemiology and risk factors

    International Nuclear Information System (INIS)

    Broeders, M. J. M.; Verbeek, A. L. M.

    1997-01-01

    Breast cancer is the most common malignancy among women in the Western society. Over the past decades it has become apparent that breast cancer incidence rates are increasing steadily, whereas the mortality rates for breast cancer have remained relatively constant. Information through the media on this rising number of cases has increased breast health awareness but has also introduced anxiety in the female population. This combination of factors has made the need for prevention of breast cancer an urgent matter. Breast cancer does not seem to be a single disease entity. A specific etiologic factor may therefore have more influence on one form may therefore have more influence on one form of breast cancer than another. So far though, as shown in their summary of current knowledge on established and dubious risk factors, no risk factors have been identified that can explain a major part of the incidence. Efforts to identify other ways for primary prevention have also been discouraging, even though breast cancer is one of the most investigated tumours world-wide. Thus, at this point i time, the most important strategy to reduce breast cancer mortality is early detection through individual counselling and organised breast screening programs. The recent isolation of breast cancer susceptibility genes may introduce new ways to reduce the risk of breast cancer in a small subset of women

  15. Adenoid cystic carcinoma of the breast

    International Nuclear Information System (INIS)

    Kallel, R.; Bahri Zouari, I.; Gouiaa, N.; Charfi, S.; Ayadi, L.; Makni, S.; Sellami Boudawara, T.; Daoud, E.; Daoud, J.

    2009-01-01

    Adenoid cystic carcinoma of the breast is a rare neoplasm, accounting for only 0.1% of all malignant breast tumours. It is more common in women in the sixth decade of their lives and often in the sub areolar area. The clinical criteria is not specific and the radiographic examination showed a benign-appearing tumour. The preoperative diagnosis is possible with fine-needle aspiration cytology. The diagnosis is made by histological examination, presented a difficult differential diagnosis with cribriform carcinoma; so it is necessary to use histochemical or immunohistochemical techniques. The treatment is not well established. It consists of lumpectomy with radiation or mastectomy. Compared to other locations, adenoid cystic carcinoma of the breast has a favorable prognosis. Lymph node involvement or distant metastases seldom occur. The aim of our study is to describe the epidemiological, clinico pathological characteristics, the treatment and the prognosis of this rare type of breast tumour. (authors)

  16. Selective sentinel node biopsy after intratumour administration of radiotracer in breast cancer patients treated with neoadjuvant chemotherapy in relation to the level of tumour response.

    Science.gov (United States)

    Díaz-Expósito, R; Martí-Bonmatí, L; Burgués, O; Casáns-Tormo, I; Bermejo-de Las Heras, B; Julve-Parreño, A; Caballero-Garate, A

    Our objective was to analyse the accuracy of the sentinel node biopsy, taking into consideration the scintigraphy detection rate after the intratumoural administration of the radiopharmaceutical in patients with breast cancer who received neoadjuvant chemotherapy. The study included 60 patients with a diagnosis of invasive breast carcinoma, stage T1-T3, who received treatment with neoadjuvant chemotherapy, and were subsequently subjected to breast surgery and sentinel node biopsy after intra-tumour administration of the radiopharmaceutical. Scintigraphic detection of some sentinel node was achieved in 55/60 patients (91.6%). When those cases that received a second injection of the radiopharmaceutical, performed peri-areolarly due to a lack of tracer migration, were excluded, the detection rate dropped to 70% (42/60). When the detection of sentinel node, or its absence, was compared in those 42 patients, no differences were found with age, laterality-location of the lesion, size pre- and post-neoadjuvant chemotherapy, histological grade, or immunohistochemical profile. There were significant differences when comparing the groups according to the degree of pathological tumour response, both with the Miller-Payne system (non-detection 44.4%-detection 16.7%, p = 0.003) as well as the residual cancer burden (72.2%-28.6%, pcancer who received neoadjuvant chemotherapy was below the optimal value, and sometimes a further, peri-areolar, injection was necessary, probably in relation to an alteration in the lymphatic drainage pathways. There was a significant inverse relationship between the detection of the sentinel node and level of pathological tumour response. Copyright © 2016 Elsevier España, S.L.U. y SEMNIM. All rights reserved.

  17. Biodistribution and SPECT imaging of 125/131I-crotoxin on mice bearing Ehrlich solid tumour

    International Nuclear Information System (INIS)

    Soares, Marcella Araugio; Santos, Raquel Gouvea dos; Silveira, Marina B.; Simal, Carlos

    2009-01-01

    The search of specific radiopharmaceuticals to be used in breast tumour diagnosis is relevant to complement the techniques applied in conventional medicine. Crotalus durissus terrificus venom (CV) and its main polypeptide, Crotoxin (Crtx), are natural source of several bioactive substances with therapeutical potential. The aim of this work was to evaluate the binding of Crtx with tumour targets in vivo, as well as, evaluate its applicability for breast tumours diagnosis. Crtx was labelled with 125/131 I using lactoperoxidase method and radiochemical analysis was performed by chromatography. 125 I-Crtx was used for biodistribution and pharmacokinetics studies on swiss mice bearing Ehrlich solid tumour, while 131 I-Crtx was used for single photon emission computed tomography (SPECT) imaging. Crtx presented specific binding sites on Ehrlich tumour cells and had a rapid blood clearance (T 1/2 = 201.1 min.). Intratumoral administration increased significantly the activity delivered into the tumour site (128-fold higher) and reduced the kidney burden (7.2-fold lower). 131 I-Crxt demonstrated to interact with tumour cells for until 72 hours allowing good quality images of tumour. Our results indicate the biotechnological potential of Crtx as template for radiopharmaceutical design for cancer diagnosis. (author)

  18. The future of breast cancer radiotherapy: From one size fits all to taylor-made treatment; L'avenir de la radiotherapie du cancer du sein: de la taille unique au sur-mesure

    Energy Technology Data Exchange (ETDEWEB)

    Hennequin, C. [Service de cancerologie-radiotherapie, hopital Saint-Louis, 1, avenue Claude-Vellefaux, 75475 Paris (France); Azria, D. [Departement de cancerologie radiotherapie, CRLC Val-d' Aurelle-Paul-Lamarque, rue Croix-Verte, 34298 Montpellier cedex 5 (France); Universite de Montpellier I, 5, boulevard Henri-IV, CS 19044, 34967 Montpellier cedex 2 (France); Inserm U896, institut de recherche en cancerologie de Montpellier, CRLC Val-d' Aurelle-Paul-Lamarque, rue Croix-Verte, 34298 Montpellier cedex 5 (France)

    2011-10-15

    Various subgroups of breast tumours have been identified during the last 10 years according to the risk of local relapse. Prognostic factors for local relapse are age, surgical margins, tumour size, Her2 expression and hormonal receptors status. For tumours with a high risk of local relapse, an increased in boost dose or the addition of new drugs (trastuzumab, anti-angiogenics, PARP inhibitors) could be considered. For low risk tumours, hypo-fractionated, accelerated partial breast and intraoperative radiotherapy are being evaluated. The classical schedule (45-50 Gy to the whole gland followed by a boost dose of 16 Gy) is no longer the universal rule. Treatment individualization, according to clinical and biological characteristics of the tumour and - possibly - to the radiobiological profile of the patient, is likely to be the future of breast cancer radiotherapy. (authors)

  19. Development of three-dimensional radiotherapy techniques in breast cancer

    Science.gov (United States)

    Coles, Charlotte E.

    Radiotherapy following conservation surgery decreases local relapse and death from breast cancer. Currently, the challenge is to minimise the morbidity caused by this treatment without losing efficacy. Despite many advances in radiation techniques in other sites of the body, the majority of breast cancer patients are still planned and treated using 2-dimensional simple radiotherapy techniques. In addition, breast irradiation currently consumes 30% of the UK's radiotherapy workload. Therefore, any change to more complex treatment should be of proven benefit. The primary objective of this research is to develop and evaluate novel radiotherapy techniques to decrease irradiation of normal structures and improve localisation of the tumour bed. I have developed a forward-planned intensity modulated (IMRT) breast radiotherapy technique, which has shown improved dosimetry results compared to standard breast radiotherapy. Subsequently, I have developed and implemented a phase III randomised controlled breast IMRT trial. This National Cancer Research Network adopted trial will answer an important question regarding the clinical benefit of breast IMRT. It will provide DNA samples linked with high quality clinical outcome data, for a national translational radiogenomics study investigating variation in normal tissue toxicity. Thus, patients with significant late normal tissue side effects despite good dose homogeneity will provide the best model for finding differences due to underlying genetics. I evaluated a novel technique using high definition free-hand 3-dimensional (3D) ultrasound in a phantom study, and the results suggested that this is an accurate and reproducible method for tumour bed localisation. I then compared recognised methods of tumour bed localisation with the 3D ultrasound method in a clinical study. The 3D ultrasound technique appeared to accurately represent the shape and spatial position of the tumour cavity. This tumour bed localisation research

  20. Through tissue imaging of a live breast cancer tumour model using handheld surface enhanced spatially offset resonance Raman spectroscopy (SESORRS).

    Science.gov (United States)

    Nicolson, Fay; Jamieson, Lauren E; Mabbott, Samuel; Plakas, Konstantinos; Shand, Neil C; Detty, Michael R; Graham, Duncan; Faulds, Karen

    2018-04-21

    In order to improve patient survival and reduce the amount of unnecessary and traumatic biopsies, non-invasive detection of cancerous tumours is of imperative and urgent need. Multicellular tumour spheroids (MTS) can be used as an ex vivo cancer tumour model, to model in vivo nanoparticle (NP) uptake by the enhanced permeability and retention (EPR) effect. Surface enhanced spatially offset Raman spectroscopy (SESORS) combines both surface enhanced Raman spectroscopy (SERS) and spatially offset Raman spectroscopy (SORS) to yield enhanced Raman signals at much greater sub-surface levels. By utilizing a reporter that has an electronic transition in resonance with the laser frequency, surface enhanced resonance Raman scattering (SERRS) yields even greater enhancement in Raman signal. Using a handheld SORS spectrometer with back scattering optics, we demonstrate the detection of live breast cancer 3D MTS containing SERRS active NPs through 15 mm of porcine tissue. False color 2D heat intensity maps were used to determine tumour model location. In addition, we demonstrate the tracking of SERRS-active NPs through porcine tissue to depths of up to 25 mm. This unprecedented performance is due to the use of red-shifted chalcogenpyrylium-based Raman reporters to demonstrate the novel technique of surface enhanced spatially offset resonance Raman spectroscopy (SESORRS) for the first time. Our results demonstrate a significant step forward in the ability to detect vibrational fingerprints from a tumour model at depth through tissue. Such an approach offers significant promise for the translation of NPs into clinical applications for non-invasive disease diagnostics based on this new chemical principle of measurement.

  1. Clinical multi-colour fluorescence imaging of malignant tumours - initial experience

    International Nuclear Information System (INIS)

    Svanberg, K.; Wang, I.; Montan, S.; Andersson-Engels, S.; Svanberg, S.; Lund Inst. of Technology

    1998-01-01

    The purpose of this study was to present a new technique for non-invasive tumour detection based on tissue fluorescence imaging. A clinically adapted multi-colour fluorescence system was employed in the real-time imaging of malignant tumours of the skin, breast, head and neck region, and urinary bladder. Tumour detection was based on the contrast displayed in fluorescence between normal and malignant tissue, related to the selective uptake of tumour-marking agents and natural chromophore differences between various tissues. In order to demarcate basal cell carcinomas of the skin, ALA was applied topically 4-6 h before the fluorescence investigation. For urinary bladder tumour visualisation, ALA was instilled into the bladder 1-2 h prior to the study. Malignant and premalignant lesions in the head and neck region were imaged after i.v. injection of HPD (Photofrin). The tumour imaging system was coupled to an endoscope. Fluorescence light emission from the tissue surface was induced with 100-ns-long optical pulses at 390 nm, generated from a frequency-doubled alexandrite laser. With the use of special image-splitting optics, the tumour fluorescence, intensified in a micro-channel plate, was imaged in 3 selected wavelength bands. These 3 images were processed together to form a new optimised-contrast image of the tumour. This image, updated at a rate of about 3 frames/s was mixed with a normal colour video image of the tissue. A clear demarcation from normal surrounding tissue was found during in vivo measurements of superficial bladder carcinoma, basal cell carcinoma of the skin, and leukoplakia with dysplasia of the lip, and in vitro investigations of resected breast cancer. (orig./MG)

  2. Neutrophil-induced transmigration of tumour cells treated with tumour-conditioned medium is facilitated by granulocyte-macrophage colony-stimulating factor.

    LENUS (Irish Health Repository)

    Wu, Q D

    2012-02-03

    OBJECTIVE: To investigate the effect of different cytokines that are present in tumour-conditioned medium on human neutrophil (PMN)-induced tumour cell transmigration. DESIGN: Laboratory study. SETTING: University hospital, Ireland. MATERIAL: Isolated human PMN and cultured human breast tumour cell line, MDA-MB-231. Interventions: Human PMN treated with either tumour-conditioned medium or different media neutralised with monoclonal antibodies (MoAb), and MDA-MB-231 cells were plated on macrovascular and microvascular endothelial monolayers in collagen-coated transwells to assess migration of tumour cells. MAIN OUTCOME MEASURES: Cytokines present in tumour-conditioned medium, PMN cytocidal function and receptor expression, and tumour cell transmigration. RESULTS: tumour-conditioned medium contained high concentrations of granulocyte-macrophage colony-stimulating factor (GM-CSF), vascular endothelial growth factor (VEGF), and interleukin 8 (IL-8), but not granulocyte colony-stimulating factor (G-CSF) and interleukin 3 (IL-3). Anti-GM-CSF MoAb significantly reduced PMN-induced transmigration of tumour cells treated with tumour-conditioned medium (p < 0.05), whereas anti-VEGF and anti-IL-8 MoAbs did not affect their migration. In addition, anti-GM-CSF MoAb, but not anti-VEGF or anti-IL-8 MoAb, reduced PMN CD11b and CD18 overexpression induced by tumour-conditioned medium (p < 0.05). CONCLUSION: These results indicate that the GM-CSF that is present in tumour-conditioned medium may be involved, at least in part, in alterations in PMN function mediated by the medium and subsequently PMN-induced transmigration of tumour cells.

  3. Diffusion-weighted imaging is helpful in the accurate non-invasive diagnosis of breast abscess: correlation with necrotic breast cancer.

    Science.gov (United States)

    Wang, Cuiyan; Eghtedari, Mohammad; Yang, Wei Tse; Dogan, Basak Erguvan

    2018-03-22

    Clinical differentiation of atypical breast abscesses from necrotic tumour in premenopausal women is challenging and may delay appropriate therapy. In this case report, we present a 36-year-old woman with signs, symptoms and conventional imaging features of malignancy who underwent breast MRI. On diffusion-weighted imaging (DWI), profoundly low apparent diffusion coefficient values were a distinguishing sign of breast abscess from necrotic breast cancer, and helped manage the patient conservatively. We present a companion case of necrotic breast tumour highlighting significant differences in DWI. © BMJ Publishing Group Ltd (unless otherwise stated in the text of the article) 2018. All rights reserved. No commercial use is permitted unless otherwise expressly granted.

  4. Prognostic relevance at 5 years of the early monitoring of neoadjuvant chemotherapy using 18F-FDG PET in luminal HER2-negative breast cancer

    International Nuclear Information System (INIS)

    Humbert, Olivier; Brunotte, Francois; Berriolo-Riedinger, Alina; Toubeau, Michel; Dygai-Cochet, Inna; Cochet, Alexandre; Gauthier, Melanie; Charon-Barra, Celine; Guiu, Severine; Desmoulins, Isabelle; Fumoleau, Pierre; Coutant, Charles

    2014-01-01

    The objective of this study was to evaluate, in the luminal human epidermal growth factor receptor 2 (HER2)-negative breast cancer subtype, the prognostic value of tumour glucose metabolism at baseline and of its early changes during neoadjuvant chemotherapy (NAC). This prospective study included 61 women with hormone-sensitive HER2-negative breast cancer treated with NAC. 18 F-Fluorodeoxyglucose (FDG) positron emission tomography (PET) was performed at baseline. Hepatic activity was used as a reference to distinguish between low metabolic and hypermetabolic tumours. In hypermetabolic tumours, a PET exam was repeated after the first course of NAC. The relative change in the maximum standardized uptake value of the tumour (∇SUV) was calculated. Nineteen women had low metabolic luminal breast cancers at baseline, correlated with low proliferation indexes. Forty-two women had hypermetabolic tumours, corresponding to more proliferative breast cancers with higher Ki-67 expression (p = 0.017) and higher grade (p = 0.04). The median follow-up period was 64.2 months (range 11.5-93.2). Thirteen women developed recurrent disease, nine of whom died. Worse overall survival was associated with larger tumour size [>5 cm, hazard ratio (HR) = 6.52, p = 0.009] and with hypermetabolic tumours achieving a low metabolic response after one cycle of NAC (ΔSUV < 16 %, HR = 10.63, p = 0.004). Five-year overall survival in these poor responder patients was 49.2 %. Overall survival in women with low metabolic tumours or hypermetabolic/good response tumours was 100 and 96.15 %, respectively. In luminal HER2-negative breast tumours, tumour metabolism at baseline and changes after the first course of NAC are early surrogate markers of patients' survival. A subgroup of women with hypermetabolic/poorly responding tumours, correlated with poor prognosis at 5 years, can be identified early. These results may guide future studies by tailoring the NAC regimen to the metabolic response. (orig.)

  5. Primary Breast Burkitt’s Lymphoma in an HIV-Infected Woman

    Directory of Open Access Journals (Sweden)

    Bangaly Traoré

    2015-01-01

    Full Text Available A 30-year-old HIV positive woman presented with a multifocal mass tumour associated with axillary and lateral-cervical lymphadenopathy in the right breast. Laboratory examination of the biopsy confirmed a case of mammary Burkitt’s lymphoma with a nodular infiltration of the breast. Antiretroviral treatment and chemotherapy were effective to control the tumour. Although Burkitt’s lymphoma rarely involves the breasts, it should be considered during routine breast examination of African woman.

  6. Gamma-ray detector guidance of breast cancer therapy

    Science.gov (United States)

    Ravi, Ananth

    2009-12-01

    Breast cancer is the most common form of cancer in women. Over 75% of breast cancer patients are eligible for breast conserving therapy. Breast conserving therapy involves a lumpectomy to excise the gross tumour, followed by adjuvant radiation therapy to eradicate residual microscopic disease. Recent advances in the understanding of breast cancer biology and recurrence have presented the opportunity to improve breast conserving therapy techniques. This thesis has explored the potential of gamma-ray detecting technology to improve guidance of both surgical and adjuvant radiation therapy aspects of breast conserving therapy. The task of accurately excising the gross tumour during breast conserving surgery (BCS) is challenging, due to the limited guidance currently available to surgeons. Radioimmuno guided surgery (RIGS) has been investigated to determine its potential to delineate the gross tumour intraoperatively. The effects of varying a set of user controllable parameters on the ability of RIGS to detect and delineate model breast tumours was determined. The parameters studied were: Radioisotope, blood activity concentration, collimator height and energy threshold. The most sensitive combination of parameters was determined to be an 111Indium labelled radiopharmaceutical with a gamma-ray detecting probe collimated to a height of 5 mm and an energy threshold at the Compton backscatter peak. Using these parameters it was found that, for the breast tumour model used, the minimum tumour-to-background ratio required to delineate the tumour edge accurately was 5.2+/-0.4 at a blood activity concentration of 5 kBq/ml. Permanent breast seed implantation (PBSI) is a form of accelerated partial breast irradiation that dramatically reduces the treatment burden of adjuvant radiation therapy on patients. Unfortunately, it is currently difficult to localize the implanted brachytherapy seeds, making it difficult to perform a correction in the event that seeds have been misplaced

  7. ATM induction insufficiency in a radiosensitive breast-cancer patient

    International Nuclear Information System (INIS)

    Clarke, R.A.; Fang, Z.H.; Marr, P.J.; Kearsley, J.H.; Papadatos, G.; Lee, C.S.; University of Sydney, Camperdown, NSW

    2002-01-01

    ATM induction insufficiency in a radiosensitive breast-cancer patient The ataxia telangiectasia (A-T) gene (ATM) is a dominant breast cancer gene with tumour suppressor activity. ATM also regulates cellular sensitivity to ionising radiation (IR) presumably through its role as a facilitator of DNA repair. In normal cells and tissues the ATM protein is rapidly induced by IR to threshold/maximum levels. The kinase function of the ATM protein is also rapidly activated in response to IR. The fact that women carriers of ATM mutations can have an increased risk of developing breast cancer and that many sporadic breast tumours have reduced levels of the ATM protein broadens the scope of ATM's tumour suppressor within the breast. This report describes the downregulation of ATM protein levels in a radiosensitive breast cancer patient. Postinduction ATM levels were up to tenfold lower in the patient's fresh tissues compared to normal controls. These results might indicate a much broader role for ATM anomalies in breast cancer aetiology. Copyright (2002) Blackwell Science Pty Ltd

  8. Functional genomics identifies specific vulnerabilities in PTEN-deficient breast cancer.

    Science.gov (United States)

    Tang, Yew Chung; Ho, Szu-Chi; Tan, Elisabeth; Ng, Alvin Wei Tian; McPherson, John R; Goh, Germaine Yen Lin; Teh, Bin Tean; Bard, Frederic; Rozen, Steven G

    2018-03-22

    Phosphatase and tensin homolog (PTEN) is one of the most frequently inactivated tumor suppressors in breast cancer. While PTEN itself is not considered a druggable target, PTEN synthetic-sick or synthetic-lethal (PTEN-SSL) genes are potential drug targets in PTEN-deficient breast cancers. Therefore, with the aim of identifying potential targets for precision breast cancer therapy, we sought to discover PTEN-SSL genes present in a broad spectrum of breast cancers. To discover broad-spectrum PTEN-SSL genes in breast cancer, we used a multi-step approach that started with (1) a genome-wide short interfering RNA (siRNA) screen of ~ 21,000 genes in a pair of isogenic human mammary epithelial cell lines, followed by (2) a short hairpin RNA (shRNA) screen of ~ 1200 genes focused on hits from the first screen in a panel of 11 breast cancer cell lines; we then determined reproducibility of hits by (3) identification of overlaps between our results and reanalyzed data from 3 independent gene-essentiality screens, and finally, for selected candidate PTEN-SSL genes we (4) confirmed PTEN-SSL activity using either drug sensitivity experiments in a panel of 19 cell lines or mutual exclusivity analysis of publicly available pan-cancer somatic mutation data. The screens (steps 1 and 2) and the reproducibility analysis (step 3) identified six candidate broad-spectrum PTEN-SSL genes (PIK3CB, ADAMTS20, AP1M2, HMMR, STK11, and NUAK1). PIK3CB was previously identified as PTEN-SSL, while the other five genes represent novel PTEN-SSL candidates. Confirmation studies (step 4) provided additional evidence that NUAK1 and STK11 have PTEN-SSL patterns of activity. Consistent with PTEN-SSL status, inhibition of the NUAK1 protein kinase by the small molecule drug HTH-01-015 selectively impaired viability in multiple PTEN-deficient breast cancer cell lines, while mutations affecting STK11 and PTEN were largely mutually exclusive across large pan-cancer data sets. Six genes showed PTEN

  9. Prognostic relevance at 5 years of the early monitoring of neoadjuvant chemotherapy using {sup 18}F-FDG PET in luminal HER2-negative breast cancer

    Energy Technology Data Exchange (ETDEWEB)

    Humbert, Olivier; Brunotte, Francois [Centre GF Leclerc, Department of Nuclear Medicine, Dijon (France); CHU Le Bocage, Imaging Department, Dijon (France); Universite de Bourgogne, UMR CNRS 5158, Dijon (France); Berriolo-Riedinger, Alina; Toubeau, Michel; Dygai-Cochet, Inna [Centre GF Leclerc, Department of Nuclear Medicine, Dijon (France); Cochet, Alexandre [Centre GF Leclerc, Department of Nuclear Medicine, Dijon (France); Universite de Bourgogne, UMR CNRS 5158, Dijon (France); Gauthier, Melanie [Centre GF Leclerc, Biostatistics and Quality of Life Unit, EA 4184, Dijon (France); Charon-Barra, Celine [Centre GF Leclerc, Department of Pathology, Dijon (France); Guiu, Severine; Desmoulins, Isabelle; Fumoleau, Pierre [Centre GF Leclerc, Department of Medical Oncology, Dijon (France); Coutant, Charles [Centre GF Leclerc, Department of Surgery, Dijon (France)

    2014-03-15

    The objective of this study was to evaluate, in the luminal human epidermal growth factor receptor 2 (HER2)-negative breast cancer subtype, the prognostic value of tumour glucose metabolism at baseline and of its early changes during neoadjuvant chemotherapy (NAC). This prospective study included 61 women with hormone-sensitive HER2-negative breast cancer treated with NAC. {sup 18}F-Fluorodeoxyglucose (FDG) positron emission tomography (PET) was performed at baseline. Hepatic activity was used as a reference to distinguish between low metabolic and hypermetabolic tumours. In hypermetabolic tumours, a PET exam was repeated after the first course of NAC. The relative change in the maximum standardized uptake value of the tumour (∇SUV) was calculated. Nineteen women had low metabolic luminal breast cancers at baseline, correlated with low proliferation indexes. Forty-two women had hypermetabolic tumours, corresponding to more proliferative breast cancers with higher Ki-67 expression (p = 0.017) and higher grade (p = 0.04). The median follow-up period was 64.2 months (range 11.5-93.2). Thirteen women developed recurrent disease, nine of whom died. Worse overall survival was associated with larger tumour size [>5 cm, hazard ratio (HR) = 6.52, p = 0.009] and with hypermetabolic tumours achieving a low metabolic response after one cycle of NAC (ΔSUV < 16 %, HR = 10.63, p = 0.004). Five-year overall survival in these poor responder patients was 49.2 %. Overall survival in women with low metabolic tumours or hypermetabolic/good response tumours was 100 and 96.15 %, respectively. In luminal HER2-negative breast tumours, tumour metabolism at baseline and changes after the first course of NAC are early surrogate markers of patients' survival. A subgroup of women with hypermetabolic/poorly responding tumours, correlated with poor prognosis at 5 years, can be identified early. These results may guide future studies by tailoring the NAC regimen to the metabolic response

  10. [Partial breast irradiation (PBI): the therapy of the future?].

    Science.gov (United States)

    Koning, Caro C E; Bijker, Nina; van Tienhoven, Geertjan

    2010-01-01

    Breast-conserving therapy with radiation therapy of 50 Gy over 5 weeks to the entire breast plus a tumour bed boost is the standard treatment for patients with early stage breast cancer. Several attempts have been made to lower the treatment burden, such as omitting either all radiotherapy or the tumour bed boost, without success. Phase III trials are now being carried out to evaluate the treatment of the primary tumour area only (PBI). Various methods for selection of patient groups and of delivering the radiation dose have been employed. Vaidya et al. report the same favourable local recurrence rates following PBI with single dose intraoperative radiotherapy as with whole-breast irradiation. As the follow-up period so far has been short, long-time results should be awaited.

  11. The integrative epigenomic-transcriptomic landscape of ER positive breast cancer.

    Science.gov (United States)

    Gao, Yang; Jones, Allison; Fasching, Peter A; Ruebner, Matthias; Beckmann, Matthias W; Widschwendter, Martin; Teschendorff, Andrew E

    2015-01-01

    While recent integrative analyses of copy number and gene expression data in breast cancer have revealed a complex molecular landscape with multiple subtypes and many oncogenic/tumour suppressor driver events, much less is known about the role of DNA methylation in shaping breast cancer taxonomy and defining driver events. Here, we applied a powerful integrative network algorithm to matched DNA methylation and RNA-Seq data for 724 estrogen receptor (ER)-positive (ER+) breast cancers and 111 normal adjacent tissue specimens from The Cancer Genome Atlas (TCGA) project, in order to identify putative epigenetic driver events and to explore the resulting molecular taxonomy. This revealed the existence of nine functionally deregulated epigenetic hotspots encompassing a total of 146 genes, which we were able to validate in independent data sets encompassing over 1000 ER+ breast cancers. Integrative clustering of the matched messenger RNA (mRNA) and DNA methylation data over these genes resulted in only two clusters, which correlated very strongly with the luminal-A and luminal B subtypes. Overall, luminal-A and luminal-B breast cancers shared the same epigenetically deregulated hotspots but with luminal-B cancers exhibiting increased aberrant DNA methylation patterns relative to normal tissue. We show that increased levels of DNA methylation and mRNA expression deviation from the normal state define a marker of poor prognosis. Our data further implicates epigenetic silencing of WNT signalling antagonists and bone morphogenetic proteins (BMP) as key events underlying both luminal subtypes but specially of luminal-B breast cancer. Finally, we show that DNA methylation changes within the identified epigenetic interactome hotspots do not exhibit mutually exclusive patterns within the same cancer sample, instead exhibiting coordinated changes within the sample. Our results indicate that the integrative DNA methylation and transcriptomic landscape of ER+ breast cancer is

  12. Classical pathological variables recorded in the Danish Breast Cancer Cooperative Group's register 1978-2006

    DEFF Research Database (Denmark)

    Kiaer, Henrik W; Laenkholm, Anne-Vibeke; Nielsen, Bernt B

    2008-01-01

    >50mm from 7 to 4%. The distribution of the histological subtypes of malignant breast tumours has been almost unchanged. We found however a significant increase in the number of high grade tumours. A large increase in the number of removed axillary lymph nodes from 1989-2001 is related to improved......The Danish Breast Cancer Cooperative Group's register containing data from about 75 000 patients undergoing surgery for primary invasive breast cancer from 1978-2006 has been examined for classical pathological variables. During that period the diagnostic approach of malignant breast tumours...

  13. Immunity to tumour antigens.

    Science.gov (United States)

    Li, Geng; Ali, Selman A; McArdle, Stephanie E B; Mian, Shahid; Ahmad, Murrium; Miles, Amanda; Rees, Robert C

    2005-01-01

    During the last decade, a large number of human tumour antigens have been identified. These antigens are classified as tumour-specific shared antigens, tissue-specific differentiation antigens, overexpressed antigens, tumour antigens resulting from mutations, viral antigens and fusion proteins. Antigens recognised by effectors of immune system are potential targets for antigen-specific cancer immunotherapy. However, most tumour antigens are self-proteins and are generally of low immunogenicity and the immune response elicited towards these tumour antigens is not always effective. Strategies to induce and enhance the tumour antigen-specific response are needed. This review will summarise the approaches to discovery of tumour antigens, the current status of tumour antigens, and their potential application to cancer treatment.

  14. Characterization of TRPS1 and ERAS as oncogenes implicated in breast cancer

    Energy Technology Data Exchange (ETDEWEB)

    Lopez Gonzalez, L.

    2015-07-01

    New high throughput technologies have made possible to identify putative oncogenes in breast cancer. In this project we aim to relate and characterise two novel putative oncogenes, ERAS and TRPS1, in their role in human breast cancer. TRPS1, an atypical GATA factor, modulates cell proliferation and controls cell cycle progression through repression of GATA-regulated genes, therefore acting as a tumour suppressor gene. Conversely, TRPS1 expression has been shown to be significantly elevated in luminal and in a lesser extent in basal breast cancer cells, presenting roles both as an oncogene and as a tumour suppressor gene in breast cancer development. The aim of this project is therefore to determine the characteristics of TRPS1 either as a putative novel human oncogene or as a tumour suppressor gene in breast cancer cells. To this aim, we have cloned a novel isoform of TRPS1 and introduced it into several breast cancer cell lines. Our results show that overexpression of this isoform of TRPS1 results in variations in motility in non-carcinogenic cell lines, as well as in a series of EMT-like changes such as the down-regulation of the EMT marker E-cadherin, both of which can be associated to an increase in malignancy, suggesting an oncogenic behaviour for TRPS1. Furthermore, our results suggest that constitutively active members of the RAS protein family induce the expression of TRPS1, establishing a relationship between both genes. We can conclude that the effects of TRPS1 overexpression are moderate, inducing some changes but not fully transforming the cells. Therefore we cannot confirm that TRPS1 is a putative oncogene in breast cancer. (Author)

  15. [Resection margins in conservative breast cancer surgery].

    Science.gov (United States)

    Medina Fernández, Francisco Javier; Ayllón Terán, María Dolores; Lombardo Galera, María Sagrario; Rioja Torres, Pilar; Bascuñana Estudillo, Guillermo; Rufián Peña, Sebastián

    2013-01-01

    Conservative breast cancer surgery is facing a new problem: the potential tumour involvement of resection margins. This eventuality has been closely and negatively associated with disease-free survival. Various factors may influence the likelihood of margins being affected, mostly related to the characteristics of the tumour, patient or surgical technique. In the last decade, many studies have attempted to find predictive factors for margin involvement. However, it is currently the new techniques used in the study of margins and tumour localisation that are significantly reducing reoperations in conservative breast cancer surgery. Copyright © 2012 AEC. Published by Elsevier Espana. All rights reserved.

  16. Association analysis identifies 65 new breast cancer risk loci

    Science.gov (United States)

    Lemaçon, Audrey; Soucy, Penny; Glubb, Dylan; Rostamianfar, Asha; Bolla, Manjeet K.; Wang, Qin; Tyrer, Jonathan; Dicks, Ed; Lee, Andrew; Wang, Zhaoming; Allen, Jamie; Keeman, Renske; Eilber, Ursula; French, Juliet D.; Chen, Xiao Qing; Fachal, Laura; McCue, Karen; McCart Reed, Amy E.; Ghoussaini, Maya; Carroll, Jason; Jiang, Xia; Finucane, Hilary; Adams, Marcia; Adank, Muriel A.; Ahsan, Habibul; Aittomäki, Kristiina; Anton-Culver, Hoda; Antonenkova, Natalia N.; Arndt, Volker; Aronson, Kristan J.; Arun, Banu; Auer, Paul L.; Bacot, François; Barrdahl, Myrto; Baynes, Caroline; Beckmann, Matthias W.; Behrens, Sabine; Benitez, Javier; Bermisheva, Marina; Bernstein, Leslie; Blomqvist, Carl; Bogdanova, Natalia V.; Bojesen, Stig E.; Bonanni, Bernardo; Børresen-Dale, Anne-Lise; Brand, Judith S.; Brauch, Hiltrud; Brennan, Paul; Brenner, Hermann; Brinton, Louise; Broberg, Per; Brock, Ian W.; Broeks, Annegien; Brooks-Wilson, Angela; Brucker, Sara Y.; Brüning, Thomas; Burwinkel, Barbara; Butterbach, Katja; Cai, Qiuyin; Cai, Hui; Caldés, Trinidad; Canzian, Federico; Carracedo, Angel; Carter, Brian D.; Castelao, Jose E.; Chan, Tsun L.; Cheng, Ting-Yuan David; Chia, Kee Seng; Choi, Ji-Yeob; Christiansen, Hans; Clarke, Christine L.; Collée, Margriet; Conroy, Don M.; Cordina-Duverger, Emilie; Cornelissen, Sten; Cox, David G; Cox, Angela; Cross, Simon S.; Cunningham, Julie M.; Czene, Kamila; Daly, Mary B.; Devilee, Peter; Doheny, Kimberly F.; Dörk, Thilo; dos-Santos-Silva, Isabel; Dumont, Martine; Durcan, Lorraine; Dwek, Miriam; Eccles, Diana M.; Ekici, Arif B.; Eliassen, A. Heather; Ellberg, Carolina; Elvira, Mingajeva; Engel, Christoph; Eriksson, Mikael; Fasching, Peter A.; Figueroa, Jonine; Flesch-Janys, Dieter; Fletcher, Olivia; Flyger, Henrik; Fritschi, Lin; Gaborieau, Valerie; Gabrielson, Marike; Gago-Dominguez, Manuela; Gao, Yu-Tang; Gapstur, Susan M.; García-Sáenz, José A.; Gaudet, Mia M.; Georgoulias, Vassilios; Giles, Graham G.; Glendon, Gord; Goldberg, Mark S.; Goldgar, David E.; González-Neira, Anna; Grenaker Alnæs, Grethe I.; Grip, Mervi; Gronwald, Jacek; Grundy, Anne; Guénel, Pascal; Haeberle, Lothar; Hahnen, Eric; Haiman, Christopher A.; Håkansson, Niclas; Hamann, Ute; Hamel, Nathalie; Hankinson, Susan; Harrington, Patricia; Hart, Steven N.; Hartikainen, Jaana M.; Hartman, Mikael; Hein, Alexander; Heyworth, Jane; Hicks, Belynda; Hillemanns, Peter; Ho, Dona N.; Hollestelle, Antoinette; Hooning, Maartje J.; Hoover, Robert N.; Hopper, John L.; Hou, Ming-Feng; Hsiung, Chia-Ni; Huang, Guanmengqian; Humphreys, Keith; Ishiguro, Junko; Ito, Hidemi; Iwasaki, Motoki; Iwata, Hiroji; Jakubowska, Anna; Janni, Wolfgang; John, Esther M.; Johnson, Nichola; Jones, Kristine; Jones, Michael; Jukkola-Vuorinen, Arja; Kaaks, Rudolf; Kabisch, Maria; Kaczmarek, Katarzyna; Kang, Daehee; Kasuga, Yoshio; Kerin, Michael J.; Khan, Sofia; Khusnutdinova, Elza; Kiiski, Johanna I.; Kim, Sung-Won; Knight, Julia A.; Kosma, Veli-Matti; Kristensen, Vessela N.; Krüger, Ute; Kwong, Ava; Lambrechts, Diether; Marchand, Loic Le; Lee, Eunjung; Lee, Min Hyuk; Lee, Jong Won; Lee, Chuen Neng; Lejbkowicz, Flavio; Li, Jingmei; Lilyquist, Jenna; Lindblom, Annika; Lissowska, Jolanta; Lo, Wing-Yee; Loibl, Sibylle; Long, Jirong; Lophatananon, Artitaya; Lubinski, Jan; Luccarini, Craig; Lux, Michael P.; Ma, Edmond S.K.; MacInnis, Robert J.; Maishman, Tom; Makalic, Enes; Malone, Kathleen E; Kostovska, Ivana Maleva; Mannermaa, Arto; Manoukian, Siranoush; Manson, JoAnn E.; Margolin, Sara; Mariapun, Shivaani; Martinez, Maria Elena; Matsuo, Keitaro; Mavroudis, Dimitrios; McKay, James; McLean, Catriona; Meijers-Heijboer, Hanne; Meindl, Alfons; Menéndez, Primitiva; Menon, Usha; Meyer, Jeffery; Miao, Hui; Miller, Nicola; Mohd Taib, Nur Aishah; Muir, Kenneth; Mulligan, Anna Marie; Mulot, Claire; Neuhausen, Susan L.; Nevanlinna, Heli; Neven, Patrick; Nielsen, Sune F.; Noh, Dong-Young; Nordestgaard, Børge G.; Norman, Aaron; Olopade, Olufunmilayo I.; Olson, Janet E.; Olsson, Håkan; Olswold, Curtis; Orr, Nick; Pankratz, V. Shane; Park, Sue K.; Park-Simon, Tjoung-Won; Lloyd, Rachel; Perez, Jose I.A.; Peterlongo, Paolo; Peto, Julian; Phillips, Kelly-Anne; Pinchev, Mila; Plaseska-Karanfilska, Dijana; Prentice, Ross; Presneau, Nadege; Prokofieva, Darya; Pugh, Elizabeth; Pylkäs, Katri; Rack, Brigitte; Radice, Paolo; Rahman, Nazneen; Rennert, Gadi; Rennert, Hedy S.; Rhenius, Valerie; Romero, Atocha; Romm, Jane; Ruddy, Kathryn J; Rüdiger, Thomas; Rudolph, Anja; Ruebner, Matthias; Rutgers, Emiel J. Th.; Saloustros, Emmanouil; Sandler, Dale P.; Sangrajrang, Suleeporn; Sawyer, Elinor J.; Schmidt, Daniel F.; Schmutzler, Rita K.; Schneeweiss, Andreas; Schoemaker, Minouk J.; Schumacher, Fredrick; Schürmann, Peter; Scott, Rodney J.; Scott, Christopher; Seal, Sheila; Seynaeve, Caroline; Shah, Mitul; Sharma, Priyanka; Shen, Chen-Yang; Sheng, Grace; Sherman, Mark E.; Shrubsole, Martha J.; Shu, Xiao-Ou; Smeets, Ann; Sohn, Christof; Southey, Melissa C.; Spinelli, John J.; Stegmaier, Christa; Stewart-Brown, Sarah; Stone, Jennifer; Stram, Daniel O.; Surowy, Harald; Swerdlow, Anthony; Tamimi, Rulla; Taylor, Jack A.; Tengström, Maria; Teo, Soo H.; Terry, Mary Beth; Tessier, Daniel C.; Thanasitthichai, Somchai; Thöne, Kathrin; Tollenaar, Rob A.E.M.; Tomlinson, Ian; Tong, Ling; Torres, Diana; Truong, Thérèse; Tseng, Chiu-chen; Tsugane, Shoichiro; Ulmer, Hans-Ulrich; Ursin, Giske; Untch, Michael; Vachon, Celine; van Asperen, Christi J.; Van Den Berg, David; van den Ouweland, Ans M.W.; van der Kolk, Lizet; van der Luijt, Rob B.; Vincent, Daniel; Vollenweider, Jason; Waisfisz, Quinten; Wang-Gohrke, Shan; Weinberg, Clarice R.; Wendt, Camilla; Whittemore, Alice S.; Wildiers, Hans; Willett, Walter; Winqvist, Robert; Wolk, Alicja; Wu, Anna H.; Xia, Lucy; Yamaji, Taiki; Yang, Xiaohong R.; Yip, Cheng Har; Yoo, Keun-Young; Yu, Jyh-Cherng; Zheng, Wei; Zheng, Ying; Zhu, Bin; Ziogas, Argyrios; Ziv, Elad; Lakhani, Sunil R.; Antoniou, Antonis C.; Droit, Arnaud; Andrulis, Irene L.; Amos, Christopher I.; Couch, Fergus J.; Pharoah, Paul D.P.; Chang-Claude, Jenny; Hall, Per; Hunter, David J.; Milne, Roger L.; García-Closas, Montserrat; Schmidt, Marjanka K.; Chanock, Stephen J.; Dunning, Alison M.; Edwards, Stacey L.; Bader, Gary D.; Chenevix-Trench, Georgia; Simard, Jacques; Kraft, Peter; Easton, Douglas F.

    2017-01-01

    Breast cancer risk is influenced by rare coding variants in susceptibility genes such as BRCA1 and many common, mainly non-coding variants. However, much of the genetic contribution to breast cancer risk remains unknown. We report results from a genome-wide association study (GWAS) of breast cancer in 122,977 cases and 105,974 controls of European ancestry and 14,068 cases and 13,104 controls of East Asian ancestry1. We identified 65 new loci associated with overall breast cancer at pcancer due to all SNPs in regulatory features was 2-5-fold enriched relative to the genome-wide average, with strong enrichment for particular transcription factor binding sites. These results provide further insight into genetic susceptibility to breast cancer and will improve the utility of genetic risk scores for individualized screening and prevention. PMID:29059683

  17. Association analysis identifies 65 new breast cancer risk loci

    DEFF Research Database (Denmark)

    Michailidou, Kyriaki; Lindström, Sara; Dennis, Joe

    2017-01-01

    Breast cancer risk is influenced by rare coding variants in susceptibility genes, such as BRCA1, and many common, mostly non-coding variants. However, much of the genetic contribution to breast cancer risk remains unknown. Here we report the results of a genome-wide association study of breast...... cancer in 122,977 cases and 105,974 controls of European ancestry and 14,068 cases and 13,104 controls of East Asian ancestry. We identified 65 new loci that are associated with overall breast cancer risk at P risk single-nucleotide polymorphisms in these loci fall......-nucleotide polymorphisms in regulatory features was 2-5-fold enriched relative to the genome-wide average, with strong enrichment for particular transcription factor binding sites. These results provide further insight into genetic susceptibility to breast cancer and will improve the use of genetic risk scores...

  18. Tumour screening by means of tomography methods

    International Nuclear Information System (INIS)

    Diederich, S.

    2005-01-01

    Tomography methods such as computer tomography (CT), magnetic resonance tomography (MRT), and sonography/ultrasound examinations make it possible to detect small asymptomatic tumours, thus potentially preventing their manifestation at an advanced stage and improving survival prospects for the patients concerned. There are data available on various common tumours which show that modern tomography methods are capable of detecting not only small asymptomatic tumours but also their benign precursors (e.g. polyps of the large intestine). This has been demonstrated for lung cancer, colon cancer and breast cancer. However, it has not been possible to date to show for any tomography method or any type of tumour that the systematic use of such diagnostic procedures does anything to lower the mortality rate for that tumour. For other types of tumour (pancreatic cancer, kidney cancer, ovary cancer) the above named methods are either not sufficiently sensitive or the body of data that has accumulated on their respective use is too small to judge the benefit of tomography screenings. Current technical developments make it appear probable that for many types of cancer the reliability with which small tumours can be detected will improve in future. Studies aimed at clarifying the potential of screenings for reducing mortality rates are already underway for lung cancer and would be worthwhile performing for other tumour types

  19. DACH1: its role as a classifier of long term good prognosis in luminal breast cancer.

    Directory of Open Access Journals (Sweden)

    Desmond G Powe

    Full Text Available BACKGROUND: Oestrogen receptor (ER positive (luminal tumours account for the largest proportion of females with breast cancer. Theirs is a heterogeneous disease presenting clinical challenges in managing their treatment. Three main biological luminal groups have been identified but clinically these can be distilled into two prognostic groups in which Luminal A are accorded good prognosis and Luminal B correlate with poor prognosis. Further biomarkers are needed to attain classification consensus. Machine learning approaches like Artificial Neural Networks (ANNs have been used for classification and identification of biomarkers in breast cancer using high throughput data. In this study, we have used an artificial neural network (ANN approach to identify DACH1 as a candidate luminal marker and its role in predicting clinical outcome in breast cancer is assessed. MATERIALS AND METHODS: A reiterative ANN approach incorporating a network inferencing algorithm was used to identify ER-associated biomarkers in a publically available cDNA microarray dataset. DACH1 was identified in having a strong influence on ER associated markers and a positive association with ER. Its clinical relevance in predicting breast cancer specific survival was investigated by statistically assessing protein expression levels after immunohistochemistry in a series of unselected breast cancers, formatted as a tissue microarray. RESULTS: Strong nuclear DACH1 staining is more prevalent in tubular and lobular breast cancer. Its expression correlated with ER-alpha positive tumours expressing PgR, epithelial cytokeratins (CK18/19 and 'luminal-like' markers of good prognosis including FOXA1 and RERG (p<0.05. DACH1 is increased in patients showing longer cancer specific survival and disease free interval and reduced metastasis formation (p<0.001. Nuclear DACH1 showed a negative association with markers of aggressive growth and poor prognosis. CONCLUSION: Nuclear DACH1 expression

  20. Breast cancer cell lines: friend or foe?

    International Nuclear Information System (INIS)

    Burdall, Sarah E; Hanby, Andrew M; Lansdown, Mark RJ; Speirs, Valerie

    2003-01-01

    The majority of breast cancer research is conducted using established breast cancer cell lines as in vitro models. An alternative is to use cultures established from primary breast tumours. Here, we discuss the pros and cons of using both of these models in translational breast cancer research

  1. Validation of cytoplasmic-to-nuclear ratio of survivin as an indicator of improved prognosis in breast cancer

    International Nuclear Information System (INIS)

    Rexhepaj, Elton; Jirstrom, Karin; O'Connor, Darran P; O'Brien, Sallyann L; Landberg, Goran; Duffy, Michael J; Brennan, Donal J; Gallagher, William M

    2010-01-01

    Conflicting data exist regarding the prognostic and predictive impact of survivin (BIRC5) in breast cancer. We previously reported survivin cytoplasmic-to-nuclear ratio (CNR) as an independent prognostic indicator in breast cancer. Here, we validate survivin CNR in a separate and extended cohort. Furthermore, we present new data suggesting that a low CNR may predict outcome in tamoxifen-treated patients. Survin expression was assessed using immunhistochemistry on a breast cancer tissue microarray (TMA) containing 512 tumours. Whole slide digital images were captured using an Aperio XT scanner. Automated image analysis was used to identify tumour from stroma and then to quantify tumour-specific nuclear and cytoplasmic survivin. A decision tree model selected using a 10-fold cross-validation approach was used to identify prognostic subgroups based on nuclear and cytoplasmic survivin expression. Following optimisation of the staining procedure, it was possible to evaluate survivin protein expression in 70.1% (n = 359) of the 512 tumours represented on the TMA. Decision tree analysis predicted that nuclear, as opposed to cytoplasmic, survivin was the most important determinant of overall survival (OS) and breast cancer-specific survival (BCSS). The decision tree model confirmed CNR of 5 as the optimum threshold for survival analysis. Univariate analysis demonstrated an association between a high CNR (>5) and a prolonged BCSS (HR 0.49, 95% CI 0.29-0.81, p = 0.006). Multivariate analysis revealed a high CNR (>5) was an independent predictor of BCSS (HR 0.47, 95% CI 0.27-0.82, p = 0.008). An increased CNR was associated with ER positive (p = 0.045), low grade (p = 0.007), Ki-67 (p = 0.001) and Her2 (p = 0.026) negative tumours. Finally, a high CNR was an independent predictor of OS in tamoxifen-treated ER-positive patients (HR 0.44, 95% CI 0.23-0.87, p = 0.018). Using the same threshold as our previous study, we have validated survivin CNR as a marker of good prognosis in

  2. Validation of cytoplasmic-to-nuclear ratio of survivin as an indicator of improved prognosis in breast cancer

    LENUS (Irish Health Repository)

    Rexhepaj, Elton

    2010-11-23

    Abstract Background Conflicting data exist regarding the prognostic and predictive impact of survivin (BIRC5) in breast cancer. We previously reported survivin cytoplasmic-to-nuclear ratio (CNR) as an independent prognostic indicator in breast cancer. Here, we validate survivin CNR in a separate and extended cohort. Furthermore, we present new data suggesting that a low CNR may predict outcome in tamoxifen-treated patients. Methods Survin expression was assessed using immunhistochemistry on a breast cancer tissue microarray (TMA) containing 512 tumours. Whole slide digital images were captured using an Aperio XT scanner. Automated image analysis was used to identify tumour from stroma and then to quantify tumour-specific nuclear and cytoplasmic survivin. A decision tree model selected using a 10-fold cross-validation approach was used to identify prognostic subgroups based on nuclear and cytoplasmic survivin expression. Results Following optimisation of the staining procedure, it was possible to evaluate survivin protein expression in 70.1% (n = 359) of the 512 tumours represented on the TMA. Decision tree analysis predicted that nuclear, as opposed to cytoplasmic, survivin was the most important determinant of overall survival (OS) and breast cancer-specific survival (BCSS). The decision tree model confirmed CNR of 5 as the optimum threshold for survival analysis. Univariate analysis demonstrated an association between a high CNR (>5) and a prolonged BCSS (HR 0.49, 95% CI 0.29-0.81, p = 0.006). Multivariate analysis revealed a high CNR (>5) was an independent predictor of BCSS (HR 0.47, 95% CI 0.27-0.82, p = 0.008). An increased CNR was associated with ER positive (p = 0.045), low grade (p = 0.007), Ki-67 (p = 0.001) and Her2 (p = 0.026) negative tumours. Finally, a high CNR was an independent predictor of OS in tamoxifen-treated ER-positive patients (HR 0.44, 95% CI 0.23-0.87, p = 0.018). Conclusion Using the same threshold as our previous study, we have

  3. Digital Microscopy Assessment of Angiogenesis in Different Breast Cancer Compartments

    Directory of Open Access Journals (Sweden)

    Anca Haisan

    2013-01-01

    Full Text Available Background/Aim. Tumour angiogenesis defined by microvessel density (MVD is generally accepted as a prognostic factor in breast cancer. However, due to variability of measurement systems and cutoffs, it is questionable to date whether it contributes to predictive outline. Our study aims to grade vascular heterogeneity by comparing clear-cut compartments: tumour associated stroma (TAS, tumour parenchyma, and tumour invasive front. Material and Methods. Computerized vessel area measurement was performed using a tissue cytometry system (TissueFAXS on slides originated from 50 patients with breast cancer. Vessels were marked using immunohistochemistry with CD34. Regions of interest were manually defined for each tumour compartment. Results. Tumour invasive front vascular endothelia area was 2.15 times higher than that in tumour parenchyma and 4.61 times higher than that in TAS (P<0.002. Worth to mention that the lymph node negative subgroup of patients show a slight but constant increase of vessel index in all examined compartments of breast tumour. Conclusion. Whole slide digital examination and region of interest (ROI analysis are a valuable tool in scoring angiogenesis markers and disclosing their prognostic capacity. Our study reveals compartments’ variability of vessel density inside the tumour and highlights the propensity of invasive front to associate an active process of angiogenesis with potential implications in adjuvant therapy.

  4. Proline-hydroxylated hypoxia-inducible factor 1α (HIF-1α upregulation in human tumours.

    Directory of Open Access Journals (Sweden)

    Cameron E Snell

    Full Text Available The stabilisation of HIF-α is central to the transcriptional response of animals to hypoxia, regulating the expression of hundreds of genes including those involved in angiogenesis, metabolism and metastasis. HIF-α is degraded under normoxic conditions by proline hydroxylation, which allows for recognition and ubiquitination by the von-Hippel-Lindau (VHL E3 ligase complex. The aim of our study was to investigate the posttranslational modification of HIF-1α in tumours, to assess whether there are additional mechanisms besides reduced hydroxylation leading to stability. To this end we optimised antibodies against the proline-hydroxylated forms of HIF-1α for use in formalin fixed paraffin embedded (FFPE immunohistochemistry to assess effects in tumour cells in vivo. We found that HIF-1α proline-hydroxylated at both VHL binding sites (Pro402 and Pro564, was present in hypoxic regions of a wide range of tumours, tumour xenografts and in moderately hypoxic cells in vitro. Staining for hydroxylated HIF-1α can identify a subset of breast cancer patients with poorer prognosis and may be a better marker than total HIF-1α levels. The expression of unhydroxylated HIF-1α positively correlates with VHL in breast cancer suggesting that VHL may be rate-limiting for HIF degradation. Our conclusions are that the degradation of proline-hydroxylated HIF-1α may be rate-limited in tumours and therefore provides new insights into mechanisms of HIF upregulation. Persistence of proline-hydroxylated HIF-1α in perinecrotic areas suggests there is adequate oxygen to support prolyl hydroxylase domain (PHD activity and proline-hydroxylated HIF-1α may be the predominant form associated with the poorer prognosis that higher levels of HIF-1α confer.

  5. Positron emission tomography of tumour [{sup 18}F]fluoroestradiol uptake in patients with acquired hormone-resistant metastatic breast cancer prior to oestradiol therapy

    Energy Technology Data Exchange (ETDEWEB)

    Kruchten, Michel van; Schroeder, Carolien P.; Vries, Elisabeth G.E. de; Hospers, Geke A.P. [University of Groningen, Department of Medical Oncology, University Medical Centre Groningen (Netherlands); Glaudemans, Andor W.J.M.; Vries, Erik F.J. de [University of Groningen, Department of Nuclear Medicine and Molecular Imaging, University Medical Centre Groningen (Netherlands)

    2015-10-15

    Whereas anti-oestrogen therapy is widely applied to treat oestrogen receptor (ER) positive breast cancer, paradoxically, oestrogens can also induce tumour regression. Up-regulation of ER expression is a marker for oestrogen hypersensitivity. We, therefore, performed an exploratory study to evaluate positron emission tomography (PET) with the tracer 16α-[{sup 18}F]fluoro-17β-oestradiol ({sup 18}F-FES) as potential marker to select breast cancer patients for oestradiol therapy. Eligible patients had acquired endocrine-resistant metastatic breast cancer that progressed after ≥2 lines of endocrine therapy. All patients had prior ER-positive histology. Treatment consisted of oestradiol 2 mg, three times daily, orally. Patients underwent {sup 18}F-FES-PET/CT imaging at baseline. Tumour {sup 18}F-FES-uptake was quantified for a maximum of 20 lesions and expressed as maximum standardised uptake value (SUV{sub max}). CT-scan was repeated every 3 months to evaluate treatment response. Clinical benefit was defined as time to radiologic or clinical progression ≥24 weeks. {sup 18}F-FES uptake, quantified for 255 lesions in 19 patients, varied greatly between lesions (median 2.8; range 0.6-24.3) and between patients (median 2.5; range 1.1-15.5). Seven (37 %) patients experienced clinical benefit of oestrogen therapy, eight progressed (PD), and four were non-evaluable due to side effects. The positive and negative predictive value (PPV/NPV) of {sup 18}F-FES-PET for response to treatment were 60 % (95 % CI: 31-83 %) and 80 % (95 % CI: 38-96 %), respectively, using SUV{sub max} >1.5. {sup 18}F-FES-PET may aid identification of patients with acquired antihormone resistant breast cancer that are unlikely to benefit from oestradiol therapy. (orig.)

  6. Mode of detection: an independent prognostic factor for women with breast cancer.

    Science.gov (United States)

    Hofvind, Solveig; Holen, Åsne; Román, Marta; Sebuødegård, Sofie; Puig-Vives, Montse; Akslen, Lars

    2016-06-01

    To investigate breast cancer survival and risk of breast cancer death by detection mode (screen-detected, interval, and detected outside the screening programme), adjusting for prognostic and predictive tumour characteristics. Information about detection mode, prognostic (age, tumour size, histologic grade, lymph node status) and predictive factors (molecular subtypes based on immunohistochemical analyses of hormone receptor status (estrogen and progesterone) and Her2 status) were available for 8344 women in Norway aged 50-69 at diagnosis of breast cancer, 2005-2011. A total of 255 breast cancer deaths were registered by the end of 2011. Kaplan-Meier method was used to estimate six years breast cancer specific survival and Cox proportional hazard model to estimate hazard ratio (HR) for breast cancer death by detection mode, adjusting for prognostic and predictive factors. Women with screen-detected cancer had favourable prognostic and predictive tumour characteristics compared with interval cancers and those detected outside the screening programme. The favourable characteristics were present for screen-detected cancers, also within the subtypes. Adjusted HR of dying from breast cancer was two times higher for women with symptomatic breast cancer (interval or outside the screening), using screen-detected tumours as the reference. Detection mode is an independent prognostic factor for women diagnosed with breast cancer. Information on detection mode might be relevant for patient management to avoid overtreatment. © The Author(s) 2015.

  7. Locoregional control and survival after breast conserving therapy

    International Nuclear Information System (INIS)

    Rajer, M.; Majdic, E.

    2006-01-01

    Background. The purpose of our study was to present a 5-year survival and locoregional control rates in breast cancer patients and to establish eventual impact of the treatment and patient characteristics on locoregional control and survival. Methods. From January 1998 to December 1999 564 stage 1 and 2 breast cancer patients were treated with breast conserving therapy. We evaluated the following characteristics: age, histological diagnosis, grade, size, number of metastatic lymph nodes, hormonal receptor status, extensive intraductal component (EIDC), vascular invasion, pathologic tumour margins, type of surgery and use of adjuvant therapy. Results. The mean age of our patients was 54.2 years. Invasive ductal carcinoma was the most common diagnosis (82.4%), followed by invasive lobular carcinoma (10.6%). Most of the tumours were grade 2. Seventy-two % of patients had T1 tumours, 24% T2 and 3% T is tumours. Metastatic lymph nodes were present in 44% of patients. All patients were treated with breast conserving surgery followed by radiotherapy (RT). Fifty % of patients received adjuvant chemotherapy and/ or hormonal therapy. The 5-year survival rate was 88.5%. Tumour size, number of metastatic lymph nodes, grade, hormonal receptors and vascular invasion proved to be statistically significant prognostic factors for the survival, while age and histological diagnosis were not. Local recurrence developed in 4.3% of our patients, while in 3.4% regional recurrence developed. Conclusions. Breast conserving surgery followed by RT was associated with good rates of locoregional control and survival, comparable to those reported in the literature. (author)

  8. Metastatic tumours to hypophysis: a report of three cases and review of literature

    Directory of Open Access Journals (Sweden)

    Tomaž Šmigoc

    2016-10-01

    Full Text Available Background. Metastatic tumours to pituitary are rare. The most frequent are metastases from breast and lung.Methods. In this paper, three cases of metastatic tumours to the pituitary are presented with panhypopituitarism as a common symptom: I a 60-year-old gentleman with metastasis of diffuse large B cell lymphoma, who presented with diabetes insipidus, II a 54-year-old lady with metastatic renal clear cell carcinoma and consequent disturbances in visual acuity, brain nerve paresis and III a 57-year-old lady with breast cancer metastasis, visual impairment and brain nerve paresis.Results. A transnasal endoscopic resection of the tumours was performed in all cases, followed by oncological treatment. All patients improved after the treatment.Conclusions. Despite the rarity of the disease, a metastatic tumour to the pituitary gland must be included in the differential diagnosis when symptoms such as diabetes insipidus, ophthalmoplegy due to brain nerve palsies, rapid course of the disease and headache are observed. In 20% to 30%, pituitary metastases are the first manifestation of a tumour of unknown origin. Surgical and adjuvant therapy may improve the quality of life. The survival and prognosis are generally poor.

  9. Tumour microembolism presenting as "primary pulmonary hypertension"

    OpenAIRE

    Hibbert, M.; Braude, S.

    1997-01-01

    Pulmonary tumour microembolism is a rare cause of pulmonary hypertension. A case of rapidly progressive pulmonary hypertension in a patient with a past history of breast carcinoma is presented. Despite active consideration and investigation for malignancy as a cause, correct diagnosis was only made at necropsy. 




  10. First clinical experience with a dedicated MRI-guided high-intensity focused ultrasound system for breast cancer ablation

    Energy Technology Data Exchange (ETDEWEB)

    Merckel, Laura G.; Knuttel, Floor M.; Peters, Nicky H.G.M.; Mali, Willem P.T.M.; Bosch, Maurice A.A.J. van den [University Medical Center Utrecht, Department of Radiology, HP E 01.132, Utrecht (Netherlands); Deckers, Roel; Moonen, Chrit T.W.; Bartels, Lambertus W. [University Medical Center Utrecht, Image Sciences Institute, Utrecht (Netherlands); Dalen, Thijs van [Diakonessenhuis Utrecht, Department of Surgery, Utrecht (Netherlands); Schubert, Gerald [Philips Healthcare, Best (Netherlands); Weits, Teun [Diakonessenhuis Utrecht, Department of Radiology, Utrecht (Netherlands); Diest, Paul J. van [University Medical Center Utrecht, Department of Pathology, Utrecht (Netherlands); Vaessen, Paul H.H.B. [University Medical Center Utrecht, Department of Anesthesiology, Utrecht (Netherlands); Gorp, Joost M.H.H. van [Diakonessenhuis Utrecht, Department of Pathology, Utrecht (Netherlands)

    2016-11-15

    To assess the safety and feasibility of MRI-guided high-intensity focused ultrasound (MR-HIFU) ablation in breast cancer patients using a dedicated breast platform. Patients with early-stage invasive breast cancer underwent partial tumour ablation prior to surgical resection. MR-HIFU ablation was performed using proton resonance frequency shift MR thermometry and an MR-HIFU system specifically designed for breast tumour ablation. The presence and extent of tumour necrosis was assessed by histopathological analysis of the surgical specimen. Pearson correlation coefficients were calculated to assess the relationship between sonication parameters, temperature increase and size of tumour necrosis at histopathology. Ten female patients underwent MR-HIFU treatment. No skin redness or burns were observed in any of the patients. No correlation was found between the applied energy and the temperature increase. In six patients, tumour necrosis was observed with a maximum diameter of 3-11 mm. In these patients, the number of targeted locations was equal to the number of areas with tumour necrosis. A good correlation was found between the applied energy and the size of tumour necrosis at histopathology (Pearson = 0.76, p = 0.002). Our results show that MR-HIFU ablation with the dedicated breast system is safe and results in histopathologically proven tumour necrosis. (orig.)

  11. Identification and prognostic value of anterior gradient protein 2 expression in breast cancer based on tissue microarray.

    Science.gov (United States)

    Guo, Jilong; Gong, Guohua; Zhang, Bin

    2017-07-01

    Breast cancer has attracted substantial attention as one of the major cancers causing death in women. It is crucial to find potential biomarkers of prognostic value in breast cancer. In this study, the expression pattern of anterior gradient protein 2 in breast cancer was identified based on the main molecular subgroups. Through analysis of 69 samples from the Gene Expression Omnibus database, we found that anterior gradient protein 2 expression was significantly higher in non-triple-negative breast cancer tissues compared with normal tissues and triple-negative breast cancer tissues (p gradient protein 2 expression pattern. Furthermore, we performed immunohistochemical analysis. The quantification results revealed that anterior gradient protein 2 is highly expressed in non-triple-negative breast cancer (grade 3 excluded) and grade 1 + 2 (triple-negative breast cancer excluded) tumours compared with normal tissues. Anterior gradient protein 2 was significantly highly expressed in non-triple-negative breast cancer (grade 3 excluded) and non-triple-negative breast cancer tissues compared with triple-negative breast cancer tissues (p gradient protein 2 was significantly highly expressed in grade 1 + 2 (triple-negative breast cancer excluded) and grade 1 + 2 tissues compared with grade 3 tissues (p gradient protein 2 expression was significantly associated with histologic type, histological grade, oestrogen status and progesterone status. Univariate analysis of clinicopathological variables showed that anterior gradient protein 2 expression, tumour size and lymph node status were significantly correlated with overall survival in patients with grade 1 and 2 tumours. Cox multivariate analysis revealed anterior gradient protein 2 as a putative independent indicator of unfavourable outcomes (p = 0.031). All these data clearly showed that anterior gradient protein 2 is highly expressed in breast cancer and can be regarded as a putative biomarker for

  12. Checkpoint Kinase 1 Expression Predicts Poor Prognosis in Nigerian Breast Cancer Patients.

    Science.gov (United States)

    Ebili, Henry Okuchukwu; Iyawe, Victoria O; Adeleke, Kikelomo Rachel; Salami, Babatunde Abayomi; Banjo, Adekunbiola Aina; Nolan, Chris; Rakha, Emad; Ellis, Ian; Green, Andrew; Agboola, Ayodeji Olayinka Johnson

    2018-02-01

    Checkpoint kinase 1 (CHEK1), a DNA damage sensor and cell death pathway stimulator, is regarded as an oncogene in tumours, where its activities are considered essential for tumourigenesis and the survival of cancer cells treated with chemotherapy and radiotherapy. In breast cancer, CHEK1 expression has been associated with an aggressive tumour phenotype, the triple-negative breast cancer subtype, an aberrant response to tamoxifen, and poor prognosis. However, the relevance of CHEK1 expression has, hitherto, not been investigated in an indigenous African population. We therefore aimed to investigate the clinicopathological, biological, and prognostic significance of CHEK1 expression in a cohort of Nigerian breast cancer cases. Tissue microarrays of 207 Nigerian breast cancer cases were tested for CHEK1 expression using immunohistochemistry. The clinicopathological, molecular, and prognostic characteristics of CHEK1-positive tumours were determined using the Chi-squared test and Kaplan-Meier and Cox regression analyses in SPSS Version 16. Nuclear expression of CHEK1 was present in 61% of breast tumours and was associated with tumour size, triple-negative cancer, basal-like phenotype, the epithelial-mesenchymal transition, p53 over-expression, DNA homologous repair pathway dysfunction, and poor prognosis. The rate expression of CHEK1 is high in Nigerian breast cancer cases and is associated with an aggressive phenotype and poor prognosis.

  13. Diffusion-weighted imaging of breast tumours at 3 Tesla and 7 Tesla: a comparison

    Energy Technology Data Exchange (ETDEWEB)

    Gruber, S.; Minarikova, L.; Zaric, O.; Chmelik, M.; Strasser, B.; Trattnig, S.; Bogner, W. [Medical University Vienna, MRCE, Department of Biomedical imaging and Image-Guided Therapy, Vienna (Austria); Christian Doppler Laboratory for Clinical Molecular MR Imaging, Vienna (Austria); Pinker, K.; Baltzer, P.; Helbich, T. [Medical University Vienna, Division of Molecular and Gender Imaging, Department of Biomedical imaging and Image-Guided Therapy, Vienna (Austria)

    2016-05-15

    To compare bilateral diffusion-weighted MR imaging (DWI) at 3 T and 7 T in the same breast tumour patients. Twenty-eight patients were included in this IRB-approved study (mean age 56 ± 16 years). Before contrast-enhanced imaging, bilateral DWI with b = 0 and 850 s/mm{sup 2} was performed in 2:56 min (3 T) and 3:48 min (7 T), using readout-segmented echo planar imaging (rs-EPI) with a 1.4 x 1.4 mm{sup 2} (3 T)/0.9 x 0.9 mm{sup 2} (7 T) in-plane resolution. Apparent diffusion coefficients (ADC), signal-to-noise (SNR) and contrast-to-noise ratios (CNR) were assessed. Twenty-eight lesions were detected (18 malignant, 10 benign). CNR and SNR were comparable at both field strengths (p > 0.3). Mean ADC values at 7 T were 4-22 % lower than at 3 T (p ≤ 0.03). An ADC threshold of 1.275 x 10{sup -3} mm{sup 2}/s resulted in a diagnostic specificity of 90 % at both field strengths. The sensitivity was 94 % and 100 % at 3 T and 7 T, respectively. 7-T DWI of the breast can be performed with 2.4-fold higher spatial resolution than 3 T, without significant differences in SNR if compared to 3 T. (orig.)

  14. The evaluation of in vitro effect of daunorubicin and tamoxifen in ehrlich ascites tumour (EAT) cells

    International Nuclear Information System (INIS)

    Topcul, M.; Topcul, F.; Oezalpan, A.

    2001-01-01

    In the most countries, breast cancer is still the most important cancer among women. It is known that Ehrlich Ascites Tumour is experimental breast cancer model in animal. The cells used in the study are hyper diploid line of Ehrlich Ascites Tumour (EAT) cells, initially provided to us from Institute of Pathology, Koln University. In the present study, an hyper diploid line which is estrogen receptor positive was used. An anthracycline-derived antibiotic, Daunorubicin (DNR, Cerubidine) is one of the clinically used anticancer drugs. DNR has been used alone or in combination with other cytotoxic agents against a variety of animal and human tumours. In vitro cell culture studies show that DNR enters the cell nuclei, inhibits nucleic acid synthesis, and arrest cell division. Tamoxifen (TAM, Nolvadex) is a semi-synthetical estrogen antagonist, used in the management of pre and post menopausal breast cancer. This drug bind to intracellular estrogen receptors, and prevents endogenous estrogens from binding to their own receptors. It is known that Ehrlich Ascites Tumour is experimental breast cancer model in animal. The cells used in the study are hyper diploid line of EAT cells initially provided to us from Institute of Pathology, Koln University. In the present study, an hyper diploid line which is Estrogen Receptor (+) was used. Estrogen Receptor levels were studied by the methods of Lippman and Huff and Raynaud et al. with minor modifications. Estrogen Receptor activity as demonstrated by dextran-coated charcoal technique is closely correlated with the clinical ability of Tamoxifen to inhibit tumour growth

  15. Biodistribution and SPECT imaging of {sup 125/131}I-crotoxin on mice bearing Ehrlich solid tumour

    Energy Technology Data Exchange (ETDEWEB)

    Soares, Marcella Araugio; Santos, Raquel Gouvea dos [Centro de Desenvolvimento da Tecnologia Nuclear (CDTN/CNEN-MG), Belo Horizonte, MG (Brazil)], e-mail: marcellaaraugio@yahoo.com.br, e-mail: santosr@cdtn.br; Silveira, Marina B.; Simal, Carlos [Universidade Federal de Minas Gerais (UFMG), Belo Horizonte, MG (Brazil). Faculdade de Medicina; Dias, Consuelo L. Fortes [Fundacao Ezequiel Dias (FUNED), Belo Horizonte, MG (Brazil)

    2009-07-01

    The search of specific radiopharmaceuticals to be used in breast tumour diagnosis is relevant to complement the techniques applied in conventional medicine. Crotalus durissus terrificus venom (CV) and its main polypeptide, Crotoxin (Crtx), are natural source of several bioactive substances with therapeutical potential. The aim of this work was to evaluate the binding of Crtx with tumour targets in vivo, as well as, evaluate its applicability for breast tumours diagnosis. Crtx was labelled with {sup 125/131}I using lactoperoxidase method and radiochemical analysis was performed by chromatography. {sup 125}I-Crtx was used for biodistribution and pharmacokinetics studies on swiss mice bearing Ehrlich solid tumour, while {sup 131}I-Crtx was used for single photon emission computed tomography (SPECT) imaging. Crtx presented specific binding sites on Ehrlich tumour cells and had a rapid blood clearance (T{sub 1/2}= 201.1 min.). Intratumoral administration increased significantly the activity delivered into the tumour site (128-fold higher) and reduced the kidney burden (7.2-fold lower). {sup 131}I-Crxt demonstrated to interact with tumour cells for until 72 hours allowing good quality images of tumour. Our results indicate the biotechnological potential of Crtx as template for radiopharmaceutical design for cancer diagnosis. (author)

  16. Interobserver variability in the delineation of the tumour bed using seroma and surgical clips based on 4DCT scan for external-beam partial breast irradiation

    International Nuclear Information System (INIS)

    Guo, Bing; Li, Jianbin; Wang, Wei; Xu, Min; Shao, Qian; Zhang, Yingjie; Liang, Chaoqian; Guo, Yanluan

    2015-01-01

    To explore the interobserver variability in the delineation of the tumour bed using seroma and surgical clips based on the four-dimensional computed tomography (4DCT) scan for external-beam partial breast irradiation (EB-PBI) during free breathing. Patients with a seroma clarity score (SCS) 3 ~ 5 and ≥5 surgical clips in the lumpectomy cavity after breast-conserving surgery who were recruited for EB-PBI underwent 4DCT simulation. Based on the ten sets of 4DCT images acquired, the tumour bed formed using the clips, the seroma, and both the clips and seroma (defined as TB C , TB S and TB C+S , respectively) were delineated by five radiation oncologists using specific guidelines. The following parameters were calculated to analyse interobserver variability: volume of the tumour bed (TB C , TB S , TB C+S ), coefficient of variation (COV C , COV S , COV C+S ), and matching degree (MD C , MD S , MD C+S ). The interobserver variability for TB C and TB C+S and for COV C and COV C+S were statistically significant (p = 0.021, 0.008, 0.002, 0.015). No significant difference was observed for TB S and COV S (p = 0.867, 0.061). Significant differences in interobserver variability were observed for MD C vs MD S , MD C vs MD C+S , MD S vs MD C+S (p = 0.000, 0.032, 0.008), the interobserver variability of MD S was smaller than that of MD C and MD C+S (MD S > MD C+S > MD C ). When the SCS was 3 ~ 5 points and the number of surgical clips was ≥5, interobserver variability was minimal for the delineation of the tumour bed based on seroma

  17. Does the degree of background enhancement in breast MRI affect the detection and staging of breast cancer?

    International Nuclear Information System (INIS)

    Uematsu, Takayoshi; Kasami, Masako; Watanabe, Junichiro

    2011-01-01

    The purpose of this study was to assess the influence of background enhancement on the detection and staging of breast cancer using MRI as an adjunct to mammography or ultrasound. One hundred forty-six bilateral breast MRI examinations were evaluated to assess the extent of a known primary tumour and to problem solve after mammography or ultrasound without adjusting for the phase in the patients' menstrual cycle. The background enhancement was classified into four categories by visual evaluation: minimal, mild, moderate and marked. In total, 131 histologically confirmed abnormal cases (104 malignant and 27 benign) and 15 normal cases were included in the analysis. There was no tumour size-related bias between the groups (p = 0.522). For the primary index tumour, the sensitivities of MRI with minimal/mild and moderate/marked background enhancement were 100% and 76% (p = 0.001), respectively. Thus, the degree of background enhancement did not affect the specificity. For evaluating tumour extent (n = 104), the accuracy of MRI with moderate/marked background enhancement (52%) was significantly lower than that with minimal/mild background enhancement (84%; p = 0.002). The degree of background enhancement affected the detection and staging of breast cancer using MRI. (orig.)

  18. Effective treatment of chemoresistant breast cancer in vitro and in vivo by a factor VII-targeted photodynamic therapy.

    Science.gov (United States)

    Duanmu, J; Cheng, J; Xu, J; Booth, C J; Hu, Z

    2011-04-26

    The purpose of this study was to test a novel, dual tumour vascular endothelial cell (VEC)- and tumour cell-targeting factor VII-targeted Sn(IV) chlorin e6 photodynamic therapy (fVII-tPDT) by targeting a receptor tissue factor (TF) as an alternative treatment for chemoresistant breast cancer using a multidrug resistant (MDR) breast cancer line MCF-7/MDR. The TF expression by the MCF-7/MDR breast cancer cells and tumour VECs in MCF-7/MDR tumours from mice was determined separately by flow cytometry and immunohistochemistry using anti-human or anti-murine TF antibodies. The efficacy of fVII-tPDT was tested in vitro and in vivo and was compared with non-targeted PDT for treatment of chemoresistant breast cancer. The in vitro efficacy was determined by a non-clonogenic assay using crystal violet staining for monolayers, and apoptosis and necrosis were assayed to elucidate the underlying mechanisms. The in vivo efficacy of fVII-tPDT was determined in a nude mouse model of subcutaneous MCF-7/MDR tumour xenograft by measuring tumour volume. To our knowledge, this is the first presentation showing that TF was expressed on tumour VECs in chemoresistant breast tumours from mice. The in vitro efficacy of fVII-tPDT was 12-fold stronger than that of ntPDT for MCF-7/MDR cancer cells, and the mechanism of action involved induction of apoptosis and necrosis. Moreover, fVII-tPDT was effective and safe for the treatment of chemoresistant breast tumours in the nude mouse model. We conclude that fVII-tPDT is effective and safe for the treatment of chemoresistant breast cancer, presumably by simultaneously targeting both the tumour neovasculature and chemoresistant cancer cells. Thus, this dual-targeting fVII-tPDT could also have therapeutic potential for the treatment of other chemoresistant cancers.

  19. Large-scale genotyping identifies 41 new loci associated with breast cancer risk.

    Science.gov (United States)

    Michailidou, Kyriaki; Hall, Per; Gonzalez-Neira, Anna; Ghoussaini, Maya; Dennis, Joe; Milne, Roger L; Schmidt, Marjanka K; Chang-Claude, Jenny; Bojesen, Stig E; Bolla, Manjeet K; Wang, Qin; Dicks, Ed; Lee, Andrew; Turnbull, Clare; Rahman, Nazneen; Fletcher, Olivia; Peto, Julian; Gibson, Lorna; Dos Santos Silva, Isabel; Nevanlinna, Heli; Muranen, Taru A; Aittomäki, Kristiina; Blomqvist, Carl; Czene, Kamila; Irwanto, Astrid; Liu, Jianjun; Waisfisz, Quinten; Meijers-Heijboer, Hanne; Adank, Muriel; van der Luijt, Rob B; Hein, Rebecca; Dahmen, Norbert; Beckman, Lars; Meindl, Alfons; Schmutzler, Rita K; Müller-Myhsok, Bertram; Lichtner, Peter; Hopper, John L; Southey, Melissa C; Makalic, Enes; Schmidt, Daniel F; Uitterlinden, Andre G; Hofman, Albert; Hunter, David J; Chanock, Stephen J; Vincent, Daniel; Bacot, François; Tessier, Daniel C; Canisius, Sander; Wessels, Lodewyk F A; Haiman, Christopher A; Shah, Mitul; Luben, Robert; Brown, Judith; Luccarini, Craig; Schoof, Nils; Humphreys, Keith; Li, Jingmei; Nordestgaard, Børge G; Nielsen, Sune F; Flyger, Henrik; Couch, Fergus J; Wang, Xianshu; Vachon, Celine; Stevens, Kristen N; Lambrechts, Diether; Moisse, Matthieu; Paridaens, Robert; Christiaens, Marie-Rose; Rudolph, Anja; Nickels, Stefan; Flesch-Janys, Dieter; Johnson, Nichola; Aitken, Zoe; Aaltonen, Kirsimari; Heikkinen, Tuomas; Broeks, Annegien; Veer, Laura J Van't; van der Schoot, C Ellen; Guénel, Pascal; Truong, Thérèse; Laurent-Puig, Pierre; Menegaux, Florence; Marme, Frederik; Schneeweiss, Andreas; Sohn, Christof; Burwinkel, Barbara; Zamora, M Pilar; Perez, Jose Ignacio Arias; Pita, Guillermo; Alonso, M Rosario; Cox, Angela; Brock, Ian W; Cross, Simon S; Reed, Malcolm W R; Sawyer, Elinor J; Tomlinson, Ian; Kerin, Michael J; Miller, Nicola; Henderson, Brian E; Schumacher, Fredrick; Le Marchand, Loic; Andrulis, Irene L; Knight, Julia A; Glendon, Gord; Mulligan, Anna Marie; Lindblom, Annika; Margolin, Sara; Hooning, Maartje J; Hollestelle, Antoinette; van den Ouweland, Ans M W; Jager, Agnes; Bui, Quang M; Stone, Jennifer; Dite, Gillian S; Apicella, Carmel; Tsimiklis, Helen; Giles, Graham G; Severi, Gianluca; Baglietto, Laura; Fasching, Peter A; Haeberle, Lothar; Ekici, Arif B; Beckmann, Matthias W; Brenner, Hermann; Müller, Heiko; Arndt, Volker; Stegmaier, Christa; Swerdlow, Anthony; Ashworth, Alan; Orr, Nick; Jones, Michael; Figueroa, Jonine; Lissowska, Jolanta; Brinton, Louise; Goldberg, Mark S; Labrèche, France; Dumont, Martine; Winqvist, Robert; Pylkäs, Katri; Jukkola-Vuorinen, Arja; Grip, Mervi; Brauch, Hiltrud; Hamann, Ute; Brüning, Thomas; Radice, Paolo; Peterlongo, Paolo; Manoukian, Siranoush; Bonanni, Bernardo; Devilee, Peter; Tollenaar, Rob A E M; Seynaeve, Caroline; van Asperen, Christi J; Jakubowska, Anna; Lubinski, Jan; Jaworska, Katarzyna; Durda, Katarzyna; Mannermaa, Arto; Kataja, Vesa; Kosma, Veli-Matti; Hartikainen, Jaana M; Bogdanova, Natalia V; Antonenkova, Natalia N; Dörk, Thilo; Kristensen, Vessela N; Anton-Culver, Hoda; Slager, Susan; Toland, Amanda E; Edge, Stephen; Fostira, Florentia; Kang, Daehee; Yoo, Keun-Young; Noh, Dong-Young; Matsuo, Keitaro; Ito, Hidemi; Iwata, Hiroji; Sueta, Aiko; Wu, Anna H; Tseng, Chiu-Chen; Van Den Berg, David; Stram, Daniel O; Shu, Xiao-Ou; Lu, Wei; Gao, Yu-Tang; Cai, Hui; Teo, Soo Hwang; Yip, Cheng Har; Phuah, Sze Yee; Cornes, Belinda K; Hartman, Mikael; Miao, Hui; Lim, Wei Yen; Sng, Jen-Hwei; Muir, Kenneth; Lophatananon, Artitaya; Stewart-Brown, Sarah; Siriwanarangsan, Pornthep; Shen, Chen-Yang; Hsiung, Chia-Ni; Wu, Pei-Ei; Ding, Shian-Ling; Sangrajrang, Suleeporn; Gaborieau, Valerie; Brennan, Paul; McKay, James; Blot, William J; Signorello, Lisa B; Cai, Qiuyin; Zheng, Wei; Deming-Halverson, Sandra; Shrubsole, Martha; Long, Jirong; Simard, Jacques; Garcia-Closas, Montse; Pharoah, Paul D P; Chenevix-Trench, Georgia; Dunning, Alison M; Benitez, Javier; Easton, Douglas F

    2013-04-01

    Breast cancer is the most common cancer among women. Common variants at 27 loci have been identified as associated with susceptibility to breast cancer, and these account for ∼9% of the familial risk of the disease. We report here a meta-analysis of 9 genome-wide association studies, including 10,052 breast cancer cases and 12,575 controls of European ancestry, from which we selected 29,807 SNPs for further genotyping. These SNPs were genotyped in 45,290 cases and 41,880 controls of European ancestry from 41 studies in the Breast Cancer Association Consortium (BCAC). The SNPs were genotyped as part of a collaborative genotyping experiment involving four consortia (Collaborative Oncological Gene-environment Study, COGS) and used a custom Illumina iSelect genotyping array, iCOGS, comprising more than 200,000 SNPs. We identified SNPs at 41 new breast cancer susceptibility loci at genome-wide significance (P breast cancer susceptibility.

  20. HumanMethylation450K Array–Identified Biomarkers Predict Tumour Recurrence/Progression at Initial Diagnosis of High-risk Non-muscle Invasive Bladder Cancer

    Directory of Open Access Journals (Sweden)

    Mark O Kitchen

    2018-01-01

    Full Text Available Background: High-risk non-muscle invasive bladder cancer (HR-NMIBC is a clinically unpredictable disease. Despite clinical risk estimation tools, many patients are undertreated with intra-vesical therapies alone, whereas others may be over-treated with early radical surgery. Molecular biomarkers, particularly DNA methylation, have been reported as predictive of tumour/patient outcomes in numerous solid organ and haematologic malignancies; however, there are few reports in HR-NMIBC and none using genome-wide array assessment. We therefore sought to identify novel DNA methylation markers of HR-NMIBC clinical outcomes that might predict tumour behaviour at initial diagnosis and help guide patient management. Patients and methods: A total of 21 primary initial diagnosis HR-NMIBC tumours were analysed by Illumina HumanMethylation450 BeadChip arrays and subsequently bisulphite Pyrosequencing. In all, 7 had not recurred at 1 year after resection and 14 had recurred and/or progressed despite intra-vesical BCG. A further independent cohort of 32 HR-NMIBC tumours (17 no recurrence and 15 recurrence and/or progression despite BCG were also assessed by bisulphite Pyrosequencing. Results: Array analyses identified 206 CpG loci that segregated non-recurrent HR-NMIBC tumours from clinically more aggressive recurrence/progression tumours. Hypermethylation of CpG cg11850659 and hypomethylation of CpG cg01149192 in combination predicted HR-NMIBC recurrence and/or progression within 1 year of diagnosis with 83% sensitivity, 79% specificity, and 83% positive and 79% negative predictive values. Conclusions: This is the first genome-wide DNA methylation analysis of a unique HR-NMIBC tumour cohort encompassing known 1-year clinical outcomes. Our analyses identified potential novel epigenetic markers that could help guide individual patient management in this clinically unpredictable disease.

  1. The pioneer factor PBX1 is a novel driver of metastatic progression in ERα-positive breast cancer

    Science.gov (United States)

    Magnani, Luca; Patten, Darren K.; Nguyen, Van T.M.; Hong, Sung-Pil; Steel, Jennifer H.; Patel, Naina; Lombardo, Ylenia; Faronato, Monica; Gomes, Ana R.; Woodley, Laura; Page, Karen; Guttery, David; Primrose, Lindsay; Garcia, Daniel Fernandez; Shaw, Jacqui; Viola, Patrizia; Green, Andrew; Nolan, Christopher; Ellis, Ian O.; Rakha, Emad A.; Shousha, Sami; Lam, Eric W.-F.; Győrffy, Balázs; Lupien, Mathieu; Coombes, R. Charles

    2015-01-01

    Over 30% of ERα breast cancer patients develop relapses and progress to metastatic disease despite treatment with endocrine therapies. The pioneer factor PBX1 translates epigenetic cues and mediates estrogen induced ERα binding. Here we demonstrate that PBX1 plays a central role in regulating the ERα transcriptional response to epidermal growth factor (EGF) signaling. PBX1 regulates a subset of EGF-ERα genes highly expressed in aggressive breast tumours. Retrospective stratification of luminal patients using PBX1 protein levels in primary cancer further demonstrates that elevated PBX1 protein levels correlate with earlier metastatic progression. In agreement, PBX1 protein levels are significantly upregulated during metastatic progression in ERα-positive breast cancer patients. Finally we reveal that PBX1 upregulation in aggressive tumours is partly mediated by genomic amplification of the PBX1 locus. Correspondingly, ERα-positive breast cancer patients carrying PBX1 amplification are characterized by poor survival. Notably, we demonstrate that PBX1 amplification can be identified in tumor derived-circulating free DNA of ERα-positive metastatic patients. Metastatic patients with PBX1 amplification are also characterized by shorter relapse-free survival. Our data identifies PBX1 amplification as a functional hallmark of aggressive ERα-positive breast cancers. Mechanistically, PBX1 amplification impinges on several critical pathways associated with aggressive ERα-positive breast cancer. PMID:26215677

  2. Alterations of monocarboxylate transporter densities during hypoxia in brain and breast tumour cells

    DEFF Research Database (Denmark)

    Cheng, Chang; Edin, Nina F Jeppesen; Lauritzen, Knut H

    2012-01-01

    Tumour cells are characterized by aerobic glycolysis, which provides biomass for tumour proliferation and leads to extracellular acidification through efflux of lactate via monocarboxylate transporters (MCTs). Deficient and spasm-prone tumour vasculature causes variable hypoxia, which favours...

  3. Heat shock protein expression in canine malignant mammary tumours

    International Nuclear Information System (INIS)

    Romanucci, Mariarita; Marinelli, Alessia; Sarli, Giuseppe; Salda, Leonardo Della

    2006-01-01

    Abnormal levels of Heat Shock Proteins (HSPs) have been observed in many human neoplasms including breast cancer and it has been demonstrated that they have both prognostic and therapeutic implications. In this study, we evaluated immunohistochemical expression of HSPs in normal and neoplastic canine mammary glands and confronted these results with overall survival (OS), in order to understand the role of HSPs in carcinogenesis and to establish their potential prognostic and/or therapeutic value. Immunohistochemical expression of Hsp27, Hsp72, Hsp73 and Hsp90 was evaluated in 3 normal canine mammary glands and 30 malignant mammary tumours (10 in situ carcinomas, 10 invasive carcinomas limited to local structures without identifiable invasion of blood or lymphatic vessels, 10 carcinomas with invasion of blood or lymphatic vessels and/or metastases to regional lymph nodes). A semi-quantitative method was used for the analysis of the results. Widespread constitutive expression of Hsp73 and Hsp90 was detected in normal tissue, Hsp72 appeared to be focally distributed and Hsp27 showed a negative to rare weak immunostaining. In mammary tumours, a significant increase in Hsp27 (P < 0.01), Hsp72 (P < 0.05) and Hsp90 (P < 0.01) expression was observed as well as a significant reduction in Hsp73 (P < 0.01) immunoreactivity compared to normal mammary gland tissue. Hsp27 demonstrated a strong positivity in infiltrating tumour cells and metaplastic squamous elements of invasive groups. High Hsp27 expression also appeared to be significantly correlated to a shorter OS (P = 0.00087). Intense immunolabelling of Hsp72 and Hsp73 was frequently detected in infiltrative or inflammatory tumour areas. Hsp90 expression was high in all tumours and, like Hsp73, it also showed an intense positivity in lymphatic emboli. These results suggest that Hsp27, Hsp72 and Hsp90 are involved in canine mammary gland carcinogenesis. In addition, Hsp27 appears to be implicated in tumour invasiveness and

  4. Radionuclide Tc-99m MDP imaging for diagnosis of bone tumour at ...

    African Journals Online (AJOL)

    F Hasford, J.H Amuasi, E.K Sosu, K Nani, T.A Sackey, M Boadu, I.K Wilson, E.C.K Addison ... breast, cervix and prostate. Breast, prostate and cervical cancers contribut-ed respectively to 34 %, 19 % and 18 % of the bone tumour cases, but only 3 % were diagnosed with osteoporo-sis (a relatively rare type of bone disease).

  5. Acetyltransferases and tumour suppression

    International Nuclear Information System (INIS)

    Phillips, A C; Vousden, Karen H

    2000-01-01

    The acetyltransferase p300 was first identified associated with the adenoviral transforming protein E1A, suggesting a potential role for p300 in the regulation of cell proliferation. Direct evidence demonstrating a role for p300 in human tumours was lacking until the recentl publication by Gayther et al, which strongly supports a role for p300 as a tumour suppressor. The authors identify truncating mutations associated with the loss or mutation of the second allele in both tumour samples and cell lines, suggesting that loss of p300 may play a role in the development of a subset of human cancers

  6. A genetic screen identifies BRCA2 and PALB2 as key regulators of G2 checkpoint maintenance

    DEFF Research Database (Denmark)

    Menzel, Tobias; Nähse-Kumpf, Viola; Kousholt, Arne Nedergaard

    2011-01-01

    To identify key connections between DNA-damage repair and checkpoint pathways, we performed RNA interference screens for regulators of the ionizing radiation-induced G2 checkpoint, and we identified the breast cancer gene BRCA2. The checkpoint was also abrogated following depletion of PALB2......, an interaction partner of BRCA2. BRCA2 and PALB2 depletion led to premature checkpoint abrogation and earlier activation of the AURORA A-PLK1 checkpoint-recovery pathway. These results indicate that the breast cancer tumour suppressors and homologous recombination repair proteins BRCA2 and PALB2 are main...

  7. DIAGNOSTIC METHODS IN BREAST CANCER DETECTION

    Directory of Open Access Journals (Sweden)

    Kristijana Hertl

    2018-02-01

    Full Text Available Background. In the world as well as in Slovenia, breast cancer is the most frequent female cancer. Due to its high incidence, it appears to be a serious health and economic problem. Content. Among other, tumour size at diagnosis, is an important prognostic factors of the course of the disease. The probability of axillary lymph node involvement as well as distant metastases is greater in larger tumours. This is the reason that encouraged the development of various diagnostic methods for early detection of small, clinically non-palpable breast tumours. Mammography, however, remains the »golden standard« of early breast cancer detection. It is the basic diagnostic method applied in all symptomatic women over 35 years of age and in asymptomatic women over 40 years of age. Ultrasonography (US, additional projections, magnetic resonance imaging (MRI and ductography are regarded as complementary diagnostic breast imaging techniques in addition to mammography. The detected changes in the breast can be further confirmed by US-, MR-guided or stereotactic biopsy. If necessary, surgical biopsy and the excision of a tissue sample, after wire or isotope localisation of the nonpalpable lesion, can be performed. Conclusions. Any of the above mentioned diagnostic methods has advantages as well as drawbacks and only detailed knowledge and understanding of each of them may assure the best option.

  8. Genome-wide association analysis identifies three new breast cancer susceptibility loci

    DEFF Research Database (Denmark)

    Ghoussaini, Maya; Fletcher, Olivia; Michailidou, Kyriaki

    2012-01-01

    Breast cancer is the most common cancer among women. To date, 22 common breast cancer susceptibility loci have been identified accounting for ∼8% of the heritability of the disease. We attempted to replicate 72 promising associations from two independent genome-wide association studies (GWAS...

  9. Does the degree of background enhancement in breast MRI affect the detection and staging of breast cancer?

    Energy Technology Data Exchange (ETDEWEB)

    Uematsu, Takayoshi [Shizuoka Cancer Center Hospital, Breast Imaging and Breast Intervention Section, Shizuoka (Japan); Kasami, Masako [Shizuoka Cancer Center Hospital, Department of Pathology, Naga-izumi, Shizuoka (Japan); Watanabe, Junichiro [Shizuoka Cancer Center Hospital, Division of Medical Oncology, Naga-izumi, Shizuoka (Japan)

    2011-11-15

    The purpose of this study was to assess the influence of background enhancement on the detection and staging of breast cancer using MRI as an adjunct to mammography or ultrasound. One hundred forty-six bilateral breast MRI examinations were evaluated to assess the extent of a known primary tumour and to problem solve after mammography or ultrasound without adjusting for the phase in the patients' menstrual cycle. The background enhancement was classified into four categories by visual evaluation: minimal, mild, moderate and marked. In total, 131 histologically confirmed abnormal cases (104 malignant and 27 benign) and 15 normal cases were included in the analysis. There was no tumour size-related bias between the groups (p = 0.522). For the primary index tumour, the sensitivities of MRI with minimal/mild and moderate/marked background enhancement were 100% and 76% (p = 0.001), respectively. Thus, the degree of background enhancement did not affect the specificity. For evaluating tumour extent (n = 104), the accuracy of MRI with moderate/marked background enhancement (52%) was significantly lower than that with minimal/mild background enhancement (84%; p = 0.002). The degree of background enhancement affected the detection and staging of breast cancer using MRI. (orig.)

  10. Gallic acid indanone and mangiferin xanthone are strong determinants of immunosuppressive anti-tumour effects of Mangifera indica L. bark in MDA-MB231 breast cancer cells.

    Science.gov (United States)

    García-Rivera, Dagmar; Delgado, René; Bougarne, Nadia; Haegeman, Guy; Berghe, Wim Vanden

    2011-06-01

    Vimang is a standardized extract derived from Mango bark (Mangifera Indica L.), commonly used as anti-inflammatory phytomedicine, which has recently been used to complement cancer therapies in cancer patients. We have further investigated potential anti-tumour effects of glucosylxanthone mangiferin and indanone gallic acid, which are both present in Vimang extract. We observed significant anti-tumour effects of both Vimang constituents in the highly aggressive and metastatic breast cancer cell type MDA-MB231. At the molecular level, mangiferin and gallic acid both inhibit classical NFκB activation by IKKα/β kinases, which results in impaired IκB degradation, NFκB translocation and NFκB/DNA binding. In contrast to the xanthone mangiferin, gallic acid further inhibits additional NFκB pathways involved in cancer cell survival and therapy resistance, such as MEK1, JNK1/2, MSK1, and p90RSK. This results in combinatorial inhibition of NFκB activity by gallic acid, which results in potent inhibition of NFκB target genes involved in inflammation, metastasis, anti-apoptosis and angiogenesis, such as IL-6, IL-8, COX2, CXCR4, XIAP, bcl2, VEGF. The cumulative NFκB inhibition by gallic acid, but not mangiferin, is also reflected at the level of cell survival, which reveals significant tumour cytotoxic effects in MDA-MB231 cells. Altogether, we identify gallic acid, besides mangiferin, as an essential anti-cancer component in Vimang extract, which demonstrates multifocal inhibition of NFκB activity in the cancer-inflammation network. Copyright © 2011 Elsevier Ireland Ltd. All rights reserved.

  11. Aggressive solitary intracranial metastatic malignant melanoma from a primary mediastinal tumour.

    Science.gov (United States)

    Sivaraju, Laxminadh; Aryan, Saritha; Hegde, Vinay S; Ghosal, Nandita; Hegde, Alangar S

    2016-08-01

    Malignant melanoma is the third most common tumour to cause cerebral metastases, following breast and lung cancer. Central nervous system metastases occur in 10-40% of patients with melanoma. Intracranial metastasis from a primary malignant melanoma of the anterior mediastinum is uncommon. We report a case of solitary intracranial metastatic melanoma arising from a primary mediastinal tumour. We then discuss the clinico-radiological features and treatment options. © The Author(s) 2016.

  12. Indications and technical aspects of brachytherapy in breast conserving treatment of breast cancer

    International Nuclear Information System (INIS)

    Erik Van, Limbergen

    2003-01-01

    Improved local control rates have been demonstrated in retrospective studies as well as in randomized trials on brachytherapy with increasing doses to the tumour bed. The higher local control obtained by interstitial breast implants, as compared to external photon or electron beam boosts, have been mainly attributed to the higher doses actually delivered to the tumour bed by these implants for the same nominal dose as compared to external beam radiotherapy (RT). On the other hand, poor cosmesis has also been correlated with radiation dose to the breast skin (radiation telangiectases), and breast tissue (retraction due to fibrosis), the latter depending not only on RT dose but also on the treated boost volume. For this reason, a possible benefit of interstitial implants will only be realized when the gain in local control goes together with minimal cosmetic damage. Therefore, the ballistic advantages of interstitial implants have to be maximally exploited: i.e. the treated volume should be maximally adapted to the target volume, and additional irradiation of the breast skin by the boost technique should be avoided. This paper deals in detail with the technical aspects of breast brachytherapy that seem to be relevant for high quality outcome. (author)

  13. [Accelerated partial breast irradiation with multicatheters during breast conserving surgery for cancer].

    Science.gov (United States)

    Rodríguez-Spiteri Sagredo, Natalia; Martínez Regueira, Fernando; Olartecoechea Linaje, Begoña; Arredondo Chaves, Jorge; Cambeiro Vázquez, Mauricio; Pina Insausti, Luis Javier; Elizalde Pérez, Arlette; y García-Lallana, Amaya; Sola Gallego, Jose Javier

    2013-10-01

    Accelerated partial breast irradiation (APBI) with multicatheters after lumpectomy for breast cancer (BC) may be an alternative to whole breast irradiation in selected patients. The aim is to show our 5 year experience. Between June 2007 and June 2012, 87 BC patients have been evaluated for APBI. Inclusion criteria were: age over 40 years, unifocal tumour, infiltrating ductal or intraductal carcinoma, tumour size smaller than 3 cm and no lymph node involvement. Complications, cosmetic results and local and distant recurrences were evaluated. Treatment was completed in 48 patients and contraindicated in 39. The average age of treated patients was 59 years. Operating time was 123 min with 9 implanted catheters in each patient. No complications were observed during surgery or radiotherapy. Patients were discharged from hospital after 4 days. Tumour size was 11 mm. Of these, 35 were infiltrating ductal and 13 intraductal carcinomas. A total of 44 patients received adjuvant treatment. Mean follow-up was 22 months with no evidence of local or distant recurrence. The cosmetic outcome was good or excellent in 66% of cases. APBI with multicatheter placed after lumpectomy for BC is feasible and safe but requires a strict selection of patients. Copyright © 2012 AEC. Published by Elsevier Espana. All rights reserved.

  14. Evaluating hepatocellular carcinoma cell lines for tumour samples using within-sample relative expression orderings of genes.

    Science.gov (United States)

    Ao, Lu; Guo, You; Song, Xuekun; Guan, Qingzhou; Zheng, Weicheng; Zhang, Jiahui; Huang, Haiyan; Zou, Yi; Guo, Zheng; Wang, Xianlong

    2017-11-01

    Concerns are raised about the representativeness of cell lines for tumours due to the culture environment and misidentification. Liver is a major metastatic destination of many cancers, which might further confuse the origin of hepatocellular carcinoma cell lines. Therefore, it is of crucial importance to understand how well they can represent hepatocellular carcinoma. The HCC-specific gene pairs with highly stable relative expression orderings in more than 99% of hepatocellular carcinoma but with reversed relative expression orderings in at least 99% of one of the six types of cancer, colorectal carcinoma, breast carcinoma, non-small-cell lung cancer, gastric carcinoma, pancreatic carcinoma and ovarian carcinoma, were identified. With the simple majority rule, the HCC-specific relative expression orderings from comparisons with colorectal carcinoma and breast carcinoma could exactly discriminate primary hepatocellular carcinoma samples from both primary colorectal carcinoma and breast carcinoma samples. Especially, they correctly classified more than 90% of liver metastatic samples from colorectal carcinoma and breast carcinoma to their original tumours. Finally, using these HCC-specific relative expression orderings from comparisons with six cancer types, we identified eight of 24 hepatocellular carcinoma cell lines in the Cancer Cell Line Encyclopedia (Huh-7, Huh-1, HepG2, Hep3B, JHH-5, JHH-7, C3A and Alexander cells) that are highly representative of hepatocellular carcinoma. Evaluated with a REOs-based prognostic signature for hepatocellular carcinoma, all these eight cell lines showed the same metastatic properties of the high-risk metastatic hepatocellular carcinoma tissues. Caution should be taken for using hepatocellular carcinoma cell lines. Our results should be helpful to select proper hepatocellular carcinoma cell lines for biological experiments. © 2017 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.

  15. Genome-wide association study identifies novel breast cancer susceptibility loci

    Science.gov (United States)

    Easton, Douglas F.; Pooley, Karen A.; Dunning, Alison M.; Pharoah, Paul D. P.; Thompson, Deborah; Ballinger, Dennis G.; Struewing, Jeffery P.; Morrison, Jonathan; Field, Helen; Luben, Robert; Wareham, Nicholas; Ahmed, Shahana; Healey, Catherine S.; Bowman, Richard; Meyer, Kerstin B.; Haiman, Christopher A.; Kolonel, Laurence K.; Henderson, Brian E.; Marchand, Loic Le; Brennan, Paul; Sangrajrang, Suleeporn; Gaborieau, Valerie; Odefrey, Fabrice; Shen, Chen-Yang; Wu, Pei-Ei; Wang, Hui-Chun; Eccles, Diana; Evans, D. Gareth; Peto, Julian; Fletcher, Olivia; Johnson, Nichola; Seal, Sheila; Stratton, Michael R.; Rahman, Nazneen; Chenevix-Trench, Georgia; Bojesen, Stig E.; Nordestgaard, Børge G.; Axelsson, Christen K.; Garcia-Closas, Montserrat; Brinton, Louise; Chanock, Stephen; Lissowska, Jolanta; Peplonska, Beata; Nevanlinna, Heli; Fagerholm, Rainer; Eerola, Hannaleena; Kang, Daehee; Yoo, Keun-Young; Noh, Dong-Young; Ahn, Sei-Hyun; Hunter, David J.; Hankinson, Susan E.; Cox, David G.; Hall, Per; Wedren, Sara; Liu, Jianjun; Low, Yen-Ling; Bogdanova, Natalia; Schürmann, Peter; Dörk, Thilo; Tollenaar, Rob A. E. M.; Jacobi, Catharina E.; Devilee, Peter; Klijn, Jan G. M.; Sigurdson, Alice J.; Doody, Michele M.; Alexander, Bruce H.; Zhang, Jinghui; Cox, Angela; Brock, Ian W.; MacPherson, Gordon; Reed, Malcolm W. R.; Couch, Fergus J.; Goode, Ellen L.; Olson, Janet E.; Meijers-Heijboer, Hanne; van den Ouweland, Ans; Uitterlinden, André; Rivadeneira, Fernando; Milne, Roger L.; Ribas, Gloria; Gonzalez-Neira, Anna; Benitez, Javier; Hopper, John L.; McCredie, Margaret; Southey, Melissa; Giles, Graham G.; Schroen, Chris; Justenhoven, Christina; Brauch, Hiltrud; Hamann, Ute; Ko, Yon-Dschun; Spurdle, Amanda B.; Beesley, Jonathan; Chen, Xiaoqing; Mannermaa, Arto; Kosma, Veli-Matti; Kataja, Vesa; Hartikainen, Jaana; Day, Nicholas E.; Cox, David R.; Ponder, Bruce A. J.; Luccarini, Craig; Conroy, Don; Shah, Mitul; Munday, Hannah; Jordan, Clare; Perkins, Barbara; West, Judy; Redman, Karen; Driver, Kristy; Aghmesheh, Morteza; Amor, David; Andrews, Lesley; Antill, Yoland; Armes, Jane; Armitage, Shane; Arnold, Leanne; Balleine, Rosemary; Begley, Glenn; Beilby, John; Bennett, Ian; Bennett, Barbara; Berry, Geoffrey; Blackburn, Anneke; Brennan, Meagan; Brown, Melissa; Buckley, Michael; Burke, Jo; Butow, Phyllis; Byron, Keith; Callen, David; Campbell, Ian; Chenevix-Trench, Georgia; Clarke, Christine; Colley, Alison; Cotton, Dick; Cui, Jisheng; Culling, Bronwyn; Cummings, Margaret; Dawson, Sarah-Jane; Dixon, Joanne; Dobrovic, Alexander; Dudding, Tracy; Edkins, Ted; Eisenbruch, Maurice; Farshid, Gelareh; Fawcett, Susan; Field, Michael; Firgaira, Frank; Fleming, Jean; Forbes, John; Friedlander, Michael; Gaff, Clara; Gardner, Mac; Gattas, Mike; George, Peter; Giles, Graham; Gill, Grantley; Goldblatt, Jack; Greening, Sian; Grist, Scott; Haan, Eric; Harris, Marion; Hart, Stewart; Hayward, Nick; Hopper, John; Humphrey, Evelyn; Jenkins, Mark; Jones, Alison; Kefford, Rick; Kirk, Judy; Kollias, James; Kovalenko, Sergey; Lakhani, Sunil; Leary, Jennifer; Lim, Jacqueline; Lindeman, Geoff; Lipton, Lara; Lobb, Liz; Maclurcan, Mariette; Mann, Graham; Marsh, Deborah; McCredie, Margaret; McKay, Michael; McLachlan, Sue Anne; Meiser, Bettina; Milne, Roger; Mitchell, Gillian; Newman, Beth; O'Loughlin, Imelda; Osborne, Richard; Peters, Lester; Phillips, Kelly; Price, Melanie; Reeve, Jeanne; Reeve, Tony; Richards, Robert; Rinehart, Gina; Robinson, Bridget; Rudzki, Barney; Salisbury, Elizabeth; Sambrook, Joe; Saunders, Christobel; Scott, Clare; Scott, Elizabeth; Scott, Rodney; Seshadri, Ram; Shelling, Andrew; Southey, Melissa; Spurdle, Amanda; Suthers, Graeme; Taylor, Donna; Tennant, Christopher; Thorne, Heather; Townshend, Sharron; Tucker, Kathy; Tyler, Janet; Venter, Deon; Visvader, Jane; Walpole, Ian; Ward, Robin; Waring, Paul; Warner, Bev; Warren, Graham; Watson, Elizabeth; Williams, Rachael; Wilson, Judy; Winship, Ingrid; Young, Mary Ann; Bowtell, David; Green, Adele; deFazio, Anna; Chenevix-Trench, Georgia; Gertig, Dorota; Webb, Penny

    2009-01-01

    Breast cancer exhibits familial aggregation, consistent with variation in genetic susceptibility to the disease. Known susceptibility genes account for less than 25% of the familial risk of breast cancer, and the residual genetic variance is likely to be due to variants conferring more moderate risks. To identify further susceptibility alleles, we conducted a two-stage genome-wide association study in 4,398 breast cancer cases and 4,316 controls, followed by a third stage in which 30 single nucleotide polymorphisms (SNPs) were tested for confirmation in 21,860 cases and 22,578 controls from 22 studies. We used 227,876 SNPs that were estimated to correlate with 77% of known common SNPs in Europeans at r2>0.5. SNPs in five novel independent loci exhibited strong and consistent evidence of association with breast cancer (P<10−7). Four of these contain plausible causative genes (FGFR2, TNRC9, MAP3K1 and LSP1). At the second stage, 1,792 SNPs were significant at the P<0.05 level compared with an estimated 1,343 that would be expected by chance, indicating that many additional common susceptibility alleles may be identifiable by this approach. PMID:17529967

  16. SPECTRUM OF NEUROENDOCRINE TUMOURS- A TERTIARY CARE CENTRE EXPERIENCE

    Directory of Open Access Journals (Sweden)

    Pasupuleti Prathima

    2016-11-01

    Full Text Available BACKGROUND Neuroendocrine tumours occur at various sites in the human body. They are considered as one of the close differentials for many tumours. Various benign and malignant tumours undergo neuroendocrine differentiation. Its incidence is slightly increasing due to advanced imaging modalities. Although rare, they can be seen in breast, gallbladder and skin. The aim of the study is to study the spectrum of neuroendocrine tumours from various sites, their clinical presentation, histomorphological features with immunohistochemistry and review of literature. MATERIALS AND METHODS This is a retrospective study for a period of 3 years (June 2013-June 2016. Surgical resection specimens were included in the study. Out of the total specimens received, 24 cases were of neuroendocrine tumours. Differential diagnosis of small round cell tumours also was considered and a panel of immunohistochemical markers were included to rule out them. Biopsy specimens were excluded from the study. RESULTS Out of the 24 cases, 18 cases were benign lesions. 6 cases were malignant lesions. Female preponderance was noted. Peak incidence was seen in 20-30 years of age group. CONCLUSION Neuroendocrine tumours can occur anywhere in the body and it should be considered in one of the differential diagnosis. Diagnosis must be accurately made.

  17. Hereditary breast cancer: from molecular pathology to tailored therapies.

    Science.gov (United States)

    Tan, D S P; Marchiò, C; Reis-Filho, J S

    2008-10-01

    Hereditary breast cancer accounts for up to 5-10% of all breast carcinomas. Recent studies have demonstrated that mutations in two high-penetrance genes, namely BRCA1 and BRCA2, are responsible for about 16% of the familial risk of breast cancer. Even though subsequent studies have failed to find another high-penetrance breast cancer susceptibility gene, several genes that confer a moderate to low risk of breast cancer development have been identified; moreover, hereditary breast cancer can be part of multiple cancer syndromes. In this review we will focus on the hereditary breast carcinomas caused by mutations in BRCA1, BRCA2, Fanconi anaemia (FANC) genes, CHK2 and ATM tumour suppressor genes. We describe the hallmark histological features of these carcinomas compared with non-hereditary breast cancers and show how an accurate histopathological diagnosis may help improve the identification of patients to be screened for mutations. Finally, novel therapeutic approaches to treat patients with BRCA1 and BRCA2 germ line mutations, including cross-linking agents and PARP inhibitors, are discussed.

  18. Technetium-99m sestamibi: an indicator of breast cancer invasiveness

    Energy Technology Data Exchange (ETDEWEB)

    Scopinaro, F. (Section of Nuclear Medicine, Dept. of Experimental Medicine, Univ. ' La Sapienza' , Rome (Italy)); Schillaci, O. (Section of Nuclear Medicine, Dept. of Experimental Medicine, Univ. ' La Sapienza' , Rome (Italy)); Scarpini, M. (1st Inst. of Surgery, Univ. ' La Sapienza' , Rome (Italy)); Mingazzini, P.L. (1st Inst. of Surgery, Univ. ' La Sapienza' , Rome (Italy)); Di Macio, L. (Section of Nuclear Medicine, Dept. of Experimental Medicine, Univ. ' La Sapienza' , Rome (Italy)); Banci, M. (Section of Nuclear Medicine, Dept. of Experimental Medicine, Univ. ' La Sapienza' , Rome (Italy)); Danieli, R. (Section of Nuclear Medicine, Dept. of Experimental Medicine, Univ. ' La Sapienza' , Rome (Italy)); Zerilli, M. (1st Inst. of Surgery, Univ. ' La Sapienza' , Rome (Italy)); Limiti, M.R. (1st Inst. of Surgery, Univ. ' La Sapienza' , Rome (Italy)); Centi Colella, A. (Section of Nuclear Medicine, Dept. of Experimental Medicine, Univ. ' La Sapienza' , Rome (Italy))

    1994-09-01

    As recently shown, angiogenesis is the most reliable marker of breast cancer invasiveness. Unfortunately it must be assessed by immunohistochemistry on tissue specimens. We have used technetium-99m sestamibi, a marker of regional blood flow in other organs that often but not always images breast cancer, to assess the invasiveness of this tumour. Nineteen patients, ten with nodal metastases and nine without any metastases, were studied with [sup 99m]Tc-sestamibi scintigraphy before operation. Angiogenesis was quantitatively assessed by immunohistochemical staining of endothelia for factor VIII. All the node-positive (N+) patients at surgical revesion showed a positive [sup 99m]Tc-sestamibi scan of the primary tumour and all the N-patients were negative. Nine out of ten N+ and sestamibi-positive tumours showed more than 135 microvessels/mm[sup 2] and one showed 99 microvessels/mm[sup 2]; by contrast there were 71.6[+-]12.1 microvessels/mm[sup 2] in the nine N- and sestamibi-negative tumours. Our study suggests that [sup 99m]Tc-sestamibi is a marker of breast cancer invasiveness: its uptake is related to angiogenesis and, possibly, to oxidative metabolism of the tumour. (orig.)

  19. The choice of radiopharmaceutical to image breast cancer

    International Nuclear Information System (INIS)

    Capriotti, G.; Scopinaro, F.; Signore, A.; Wiele, C. van de

    2004-01-01

    Breast function and development are regulated by a network of local and systemic signals which can exert either stimulatory or inhibitory effects. Many of these signals are mediated by topically produced hormones and cytokines, which are both believed to be part of complex feedback loops. These local feedback loops also play an integral part in the vascularization and invasion of malignant breast tumours. More specifically, it has been demonstrated that the disruption of physiological negative feedback loops in breast tissue may result in the loss of cell cycle control and eventually leading to local breakdown of the adjacent stroma implying interactions between breast tumour cells and their stromal environment. Novel anticancer strategies selectively interacting with breast tumour vascularization and metastasis, include blocking monoclonal antibodies, peptide hormone antagonists, peptide/toxin fusion proteins and inhibitors of signal transduction. As most of these novel drugs are cytostatic, objective response as measured by morphological imaging modalities, e.g., Computed Tomography (CT) or Magnetic Resonance Imaging (MRI) cannot be utilized as a surrogate marker for drug development, nor for clinical decision- making. Accordingly, in order to maximize the benefit from these new treatment paradigms, novel objective markers of therapeutic success are mandatory. This editorial focuses on recently developed radioligands for SPECT imaging as potential markers for the in vivo assessment of ongoing angiogenesis and metastasis in patients suffering from breast carcinoma

  20. Juvenile fibroadenoma of the breast: Treatment and literature review

    Science.gov (United States)

    Ng, Wendy K; Mrad, M Amir; Brown, Mitchell H

    2011-01-01

    It is uncommon to find palpable breast masses in young patients. Generally, such masses are benign. Juvenile fibroadenoma is the most frequent benign tumour of the breast. The present report describes a case involving a 17-year-old girl with unilateral right breast hypertrophy, for whom resection and breast reduction was effectively achieved. Resection was combined with an aesthetically pleasing outcome through breast reduction, via a wise pattern of reduction with a superior pedicle. While young patients rarely present with breast masses, the consideration of fibroadenoma in these cases is always warranted. The disconcerting appearance of the breasts for adolescents afflicted by such benign masses underscores the importance of achieving aesthetically optimal outcomes and attaining adequate tumour resection for diagnostic purposes through pathological specimens. In the present case, the young patient underwent a procedure that fulfilled both of these valuable goals through careful pre-operative planning, pedicle selection and skin resection patterns. PMID:22942662

  1. A novel duplication polymorphism in the FANCA promoter and its association with breast and ovarian cancer

    International Nuclear Information System (INIS)

    Thompson, Ella; Dragovic, Rebecca L; Stephenson, Sally-Anne; Eccles, Diana M; Campbell, Ian G; Dobrovic, Alexander

    2005-01-01

    The FANCA gene is one of the genes in which mutations lead to Fanconi anaemia, a rare autosomal recessive disorder characterised by congenital abnormalities, bone marrow failure, and predisposition to malignancy. FANCA is also a potential breast and ovarian cancer susceptibility gene. A novel allele was identified which has a tandem duplication of a 13 base pair sequence in the promoter region. We screened germline DNA from 352 breast cancer patients, 390 ovarian cancer patients and 256 normal controls to determine if the presence of either of these two alleles was associated with an increased risk of breast or ovarian cancer. The duplication allele had a frequency of 0.34 in the normal controls. There was a non-significant decrease in the frequency of the duplication allele in breast cancer patients. The frequency of the duplication allele was significantly decreased in ovarian cancer patients. However, when malignant and benign tumours were considered separately, the decrease was only significant in benign tumours. The allele with the tandem duplication does not appear to modify breast cancer risk but may act as a low penetrance protective allele for ovarian cancer

  2. A novel duplication polymorphism in the FANCA promoter and its association with breast and ovarian cancer.

    Science.gov (United States)

    Thompson, Ella; Dragovic, Rebecca L; Stephenson, Sally-Anne; Eccles, Diana M; Campbell, Ian G; Dobrovic, Alexander

    2005-04-29

    The FANCA gene is one of the genes in which mutations lead to Fanconi anaemia, a rare autosomal recessive disorder characterised by congenital abnormalities, bone marrow failure, and predisposition to malignancy. FANCA is also a potential breast and ovarian cancer susceptibility gene. A novel allele was identified which has a tandem duplication of a 13 base pair sequence in the promoter region. We screened germline DNA from 352 breast cancer patients, 390 ovarian cancer patients and 256 normal controls to determine if the presence of either of these two alleles was associated with an increased risk of breast or ovarian cancer. The duplication allele had a frequency of 0.34 in the normal controls. There was a non-significant decrease in the frequency of the duplication allele in breast cancer patients. The frequency of the duplication allele was significantly decreased in ovarian cancer patients. However, when malignant and benign tumours were considered separately, the decrease was only significant in benign tumours. The allele with the tandem duplication does not appear to modify breast cancer risk but may act as a low penetrance protective allele for ovarian cancer.

  3. A novel duplication polymorphism in the FANCA promoter and its association with breast and ovarian cancer

    Directory of Open Access Journals (Sweden)

    Campbell Ian G

    2005-04-01

    Full Text Available Abstract The FANCA gene is one of the genes in which mutations lead to Fanconi anaemia, a rare autosomal recessive disorder characterised by congenital abnormalities, bone marrow failure, and predisposition to malignancy. FANCA is also a potential breast and ovarian cancer susceptibility gene. A novel allele was identified which has a tandem duplication of a 13 base pair sequence in the promoter region. Methods We screened germline DNA from 352 breast cancer patients, 390 ovarian cancer patients and 256 normal controls to determine if the presence of either of these two alleles was associated with an increased risk of breast or ovarian cancer. Results The duplication allele had a frequency of 0.34 in the normal controls. There was a non-significant decrease in the frequency of the duplication allele in breast cancer patients. The frequency of the duplication allele was significantly decreased in ovarian cancer patients. However, when malignant and benign tumours were considered separately, the decrease was only significant in benign tumours. Conclusion The allele with the tandem duplication does not appear to modify breast cancer risk but may act as a low penetrance protective allele for ovarian cancer.

  4. The hidden sentinel node in breast cancer

    International Nuclear Information System (INIS)

    Tanis, P.J.; Sandick, J.W. van; Nieweg, O.E.; Rutgers, E.J.T.; Kroon, B.B.R.; Valdes Olmos, R.A.; Hoefnagel, C.A.

    2002-01-01

    The purpose of this study was to analyse the occurrence of non-visualisation during preoperative lymphoscintigraphy for sentinel node identification in breast cancer. Preoperative lymphoscintigraphy was performed in 495 clinically node-negative breast cancer patients (501 sentinel node procedures) after injection of technetium-99m nanocolloid. Anterior and prone lateral (hanging breast) planar images were obtained a few minutes and 4 h after injection. The sentinel node was intraoperatively identified with the aid of patent blue dye and a gamma-ray detection probe. A sentinel node was visualised on the 4-h images in 449 of 501 procedures (90%). This visualisation rate improved from 76% to 94% during the study period. Delayed imaging (5-23 h) in 19 patients whose sentinel nodes failed to show, resulted in visualisation in four of them. A repeat injection of radiocolloid in 11 patients revealed a sentinel node in six. In the end, the visualisation rate was 92%. The sentinel node was surgically retrieved in 24 of the remaining 42 patients with non-visualisation (57%). Sentinel nodes that were visualised were tumour-positive in 38% and non-visualised sentinel nodes were involved in 50% (χ 2 , P=0.17). In a multivariate regression analysis, scintigraphic non-visualisation was independently associated with increased patient age (P<0.001), decreased tracer dose (P<0.001) and increased number of tumour-positive lymph nodes (P=0.013). The use of a sufficient amount of radioactivity (at least 100 MBq) is recommended for lymphatic mapping in breast cancer, especially in elderly women. Delayed imaging and re-injection of the radioactive tracer increase the visualisation rate. The non-visualised sentinel node can be identified intraoperatively in more than half of the patients. (orig.)

  5. The hidden sentinel node in breast cancer

    Energy Technology Data Exchange (ETDEWEB)

    Tanis, P.J.; Sandick, J.W. van; Nieweg, O.E.; Rutgers, E.J.T.; Kroon, B.B.R. [Department of Surgery, Netherlands Cancer Institute, Amsterdam (Netherlands); Valdes Olmos, R.A.; Hoefnagel, C.A. [Department of Nuclear Medicine, Netherlands Cancer Institute, Amsterdam (Netherlands)

    2002-03-01

    The purpose of this study was to analyse the occurrence of non-visualisation during preoperative lymphoscintigraphy for sentinel node identification in breast cancer. Preoperative lymphoscintigraphy was performed in 495 clinically node-negative breast cancer patients (501 sentinel node procedures) after injection of technetium-99m nanocolloid. Anterior and prone lateral (hanging breast) planar images were obtained a few minutes and 4 h after injection. The sentinel node was intraoperatively identified with the aid of patent blue dye and a gamma-ray detection probe. A sentinel node was visualised on the 4-h images in 449 of 501 procedures (90%). This visualisation rate improved from 76% to 94% during the study period. Delayed imaging (5-23 h) in 19 patients whose sentinel nodes failed to show, resulted in visualisation in four of them. A repeat injection of radiocolloid in 11 patients revealed a sentinel node in six. In the end, the visualisation rate was 92%. The sentinel node was surgically retrieved in 24 of the remaining 42 patients with non-visualisation (57%). Sentinel nodes that were visualised were tumour-positive in 38% and non-visualised sentinel nodes were involved in 50% ({chi}{sup 2}, P=0.17). In a multivariate regression analysis, scintigraphic non-visualisation was independently associated with increased patient age (P<0.001), decreased tracer dose (P<0.001) and increased number of tumour-positive lymph nodes (P=0.013). The use of a sufficient amount of radioactivity (at least 100 MBq) is recommended for lymphatic mapping in breast cancer, especially in elderly women. Delayed imaging and re-injection of the radioactive tracer increase the visualisation rate. The non-visualised sentinel node can be identified intraoperatively in more than half of the patients. (orig.)

  6. Primary and secondary prevention of breast cancer.

    Science.gov (United States)

    Kolak, Agnieszka; Kamińska, Marzena; Sygit, Katarzyna; Budny, Agnieszka; Surdyka, Dariusz; Kukiełka-Budny, Bożena; Burdan, Franciszek

    2017-12-23

    Breast cancer is the most common cancer among women and is the second cancer frequently occurring worldwide of newly-diagnosed cancers. There is much evidence showing the influence of life style and environmental factors on the development of mammary gland cancer (high-fat diet, alcohol consumption, lack of physical exercise), the elimination of which (primary prevention) may contribute to a decrease in morbidity and mortality. Secondary prevention, comprising diagnostic tests (e.g. mammography, ultrasonography, magnetic resonance imaging, breast self-examination, as well as modern and more precise imaging methods) help the early detection of tumours or lesions predisposing to tumours. The aim of this study paper is to review current knowledge and reports regarding primary and secondary prevention of breast cancer. It is estimated that nearly 70% of malign tumours are caused by environmental factors, whereas in breast cancer this percentage reaches 90-95%. There are national programmes established in many countries to fight cancer, where both types of prevention are stressed as serving to decrease morbidity and mortality due to cancers. Cancer prevention is currently playing a key role in the fight against the disease. Behaviour modification, as well as greater awareness among women regarding breast cancer, may significantly contribute towards reducing the incidence of this cancer. Another important aspect is the number of women undergoing diagnostic tests, which still remains at an unsatisfactory level.

  7. Prognostic Impact of VEGFA Germline Polymorphisms in Patients with HER2-positive Primary Breast Cancer

    DEFF Research Database (Denmark)

    Maae, Else; Andersen, Rikke Fredslund; Dahl Steffensen, Karina

    2012-01-01

    Background: Vascular endothelial growth factor A (VEGFA) is essential in tumour angiogenesis, and polymorphisms in the VEGFA gene have been associated with breast cancer prognosis. The human epidermal growth factor receptor 2 (HER2) is overexpressed in breast tumours and is also associated with a...

  8. FDG-PET/CT detection of very early breast cancer in women with breast microcalcification lesions found in mammography screening

    International Nuclear Information System (INIS)

    Peng, Nang-Jing; Chou, Chen-Pin; Pan, Huay-Ben; Chang, Tsung-Hsien; Hu, Chin; Chiu, Yu-Li; Fu, Ting-Ying; Chang, Hong-Tai

    2015-01-01

    To assess the efficacy of positron emission tomography/computed tomography with the glucose analogue 2-[ 18 F]fluoro-2-deoxy-D-glucose (FDG-PET/CT) in Taiwanese women with early breast cancer detected by mammography screening. Dual-time-point imaging of whole-body supine and breast prone scans using FDG-PET/CT were performed sequentially in the pre-operative stage. A total of 11,849 patients underwent screening mammography, of whom 1,209 (10.2%) displayed positive results. After further investigation, 54 patients underwent FDG-PET/CT. Post-operative pathology examinations revealed malignancies in 26 lesions, including invasive breast cancer in 11 cases and non-invasive breast cancer in 15 cases, as well as benign disease in 30 lesions. The FDG-PET/CT findings from the whole-body scans were positive for 9 of 11 invasive breast cancers (81.8%) and 3 of 15 non-invasive cancers (20%), and they were negative for all benign lesions. The sensitivity, specificity, positive predictive value (PPV) and negative predictive value (NPV) of FDG-PET/CT with whole-body supine imaging were 46.2%, 100%, 100% and 68.2%, respectively. Breast prone imaging revealed another patient with ductal carcinoma in situ, increasing the sensitivity to 50%. Importantly, positive PET findings were significantly correlated with tumour histology (P = 0.006), tumour size (P = 0.039) and Ki-67 expression (P = 0.011). FDG-PET/CT with whole-body scanning demonstrated high sensitivity to invasive breast cancer, limited sensitivity to non-invasive breast cancer, and high specificity for breast cancer. FDG-PET/CT might be useful for differentiating tumour invasiveness. However, the good PPV but poor NPV do not allow the physician to discard the biopsy.

  9. Endostatin gene variation and protein levels in breast cancer susceptibility and severity

    International Nuclear Information System (INIS)

    Balasubramanian, Sabapathy P; Cross, Simon S; Globe, Jenny; Cox, Angela; Brown, Nicola J; Reed, Malcolm W

    2007-01-01

    Endostatin is a potent endogenous anti-angiogenic agent which inhibits tumour growth. A non-synonymous coding polymorphism in the Endostatin gene is thought to affect Endostatin activity. We aimed to determine the role of this Endostatin polymorphism in breast cancer pathogenesis and any influence on serum Endostatin levels in healthy volunteers. Endostatin protein expression on a breast cancer micro array was also studied to determine any relationship to genotype and to breast cancer prognosis. The 4349G > A (coding non-synonymous) polymorphism in exon 42 of the Endostatin gene was genotyped in approximately 846 breast cancer cases and 707 appropriate controls. In a separate healthy cohort of 57 individuals, in addition to genotyping, serum Endostatin levels were measured using enzyme linked immunosorbant assay (ELISA). A semi-quantitative assessment of Endostatin protein expression on immunostained tissue micro arrays (TMA) constructed from breast cancer samples of patients with genotype data was performed. The rare allele (A) was significantly associated with invasive breast cancers compared to non-invasive tumours (p = 0.03), but there was no association with tumour grade, nodal status, vascular invasion or overall survival. There was no association with breast cancer susceptibility. Serum Endostatin levels and Endostatin protein expression on the tissue micro array were not associated with genotype. The Endostatin 4349A allele is associated with invasive breast cancer. The Endostatin 4349G > A polymorphism however does not appear to be associated with breast cancer susceptibility or severity in invasive disease. By studying circulating levels and tumour Endostatin protein expression, we have shown that any influence of this polymorphism is unlikely to be through an effect on the levels of protein produced

  10. Comparison of 6q25 breast cancer hits from Asian and European Genome Wide Association Studies in the Breast Cancer Association Consortium (BCAC.

    Directory of Open Access Journals (Sweden)

    Rebecca Hein

    Full Text Available The 6q25.1 locus was first identified via a genome-wide association study (GWAS in Chinese women and marked by single nucleotide polymorphism (SNP rs2046210, approximately 180 Kb upstream of ESR1. There have been conflicting reports about the association of this locus with breast cancer in Europeans, and a GWAS in Europeans identified a different SNP, tagged here by rs12662670. We examined the associations of both SNPs in up to 61,689 cases and 58,822 controls from forty-four studies collaborating in the Breast Cancer Association Consortium, of which four studies were of Asian and 39 of European descent. Logistic regression was used to estimate odds ratios (OR and 95% confidence intervals (CI. Case-only analyses were used to compare SNP effects in Estrogen Receptor positive (ER+ versus negative (ER- tumours. Models including both SNPs were fitted to investigate whether the SNP effects were independent. Both SNPs are significantly associated with breast cancer risk in both ethnic groups. Per-allele ORs are higher in Asian than in European studies [rs2046210: OR (A/G = 1.36 (95% CI 1.26-1.48, p = 7.6 × 10(-14 in Asians and 1.09 (95% CI 1.07-1.11, p = 6.8 × 10(-18 in Europeans. rs12662670: OR (G/T = 1.29 (95% CI 1.19-1.41, p = 1.2 × 10(-9 in Asians and 1.12 (95% CI 1.08-1.17, p = 3.8 × 10(-9 in Europeans]. SNP rs2046210 is associated with a significantly greater risk of ER- than ER+ tumours in Europeans [OR (ER- = 1.20 (95% CI 1.15-1.25, p = 1.8 × 10(-17 versus OR (ER+ = 1.07 (95% CI 1.04-1.1, p = 1.3 × 10(-7, p(heterogeneity = 5.1 × 10(-6]. In these Asian studies, by contrast, there is no clear evidence of a differential association by tumour receptor status. Each SNP is associated with risk after adjustment for the other SNP. These results suggest the presence of two variants at 6q25.1 each independently associated with breast cancer risk in Asians and in Europeans. Of these two, the one tagged by rs2046210 is associated with a greater

  11. Radiographer-led breast boost localisation – A service evaluation study

    International Nuclear Information System (INIS)

    Smith, S.; Comins, C.

    2015-01-01

    A radiation boost to the tumour bed as part of breast conserving therapy reduces the rate of local recurrence. Radiographer-led planning for tangential field radiotherapy has been the practice at our centre since 2007. The transition from conventional simulation to computed tomography (CT) and virtual simulation enhanced the radiographer's role in the breast planning process. Electron boost mark ups continued to be marked up freehand by doctors using available imaging to determine tumour bed. The paper reports on a service evaluation undertaken to establish a change in practice for electron breast boosts to be simulated using the virtual simulator by suitably trained radiographers. The retrospective simulation of ten patients confirmed the consistency of radiographer tumour bed localisation, followed by the prospective simulation of ten patients' boost fields. The introduction of a radiographer-led planning breast boost service has given greater autonomy and job satisfaction to individuals as well as resulting in a cost effective use of available resources. - Highlights: • A service evaluation study was undertaken to train a radiographer to perform breast boost planning. • Retrospective breast boost planning established proposed technique was workable. • Prospective planning by radiographer proved their competence. • Introduction of new technique provided job satisfaction and service improvement

  12. Identifying Two Common Types of Breast Benign Diseases Based on Multiphoton Microscopy

    Directory of Open Access Journals (Sweden)

    Yan Wu

    2018-01-01

    Full Text Available Multiphoton microscopy has attracted increasing attention and investigations in the field of breast cancer, based on two-photon excited fluorescence (TPEF and second-harmonic generation (SHG. However, the incidence of breast benign diseases is about 5 to 10 times higher than breast cancer; up to 30% of women suffer from breast benign diseases and require treatment at some time in their lives. Thus, in this study, MPM was applied to image fibroadenoma and fibrocystic lesion, which are two of the most common breast benign diseases. The results show that MPM has the capability to identify the microstructure of lobule and stroma in normal breast tissue, the interaction of compressed ducts with surrounding collagen fiber in fibroadenoma, and the architecture of cysts filled with cystic fluid in fibrocystic disease. These findings indicate that, with integration of MPM into currently accepted clinical imaging system, it has the potential to make a real-time diagnosis of breast benign diseases in vivo, as well as breast cancer.

  13. Gene Expression Signature TOPFOX Reflecting Chromosomal Instability Refines Prediction of Prognosis in Grade 2 Breast Cancer

    DEFF Research Database (Denmark)

    Szasz, A.; Li, Qiyuan; Sztupinszki, Z.

    2011-01-01

    Purpose: To assess the ability of genes selected from those reflecting chromosomal instability to identify good and poor prognostic subsets of Grade 2 breast carcinomas. Methods: We selected genes for splitting grade 2 tumours into low and high grade type groups by using public databases. Patient...

  14. Axillary fine needle aspiration cytology for pre-operative staging of patients with screen-detected invasive breast carcinoma.

    LENUS (Irish Health Repository)

    Hayes, Brian D

    2012-02-01

    INTRODUCTION: Fine needle aspiration cytology (FNAC) of radiologically abnormal axillary lymph nodes in patients with breast cancer can identify patients suitable for primary axillary clearance (AC) rather than sentinel node biopsy, enabling surgical axillary staging by a single operation. This study assessed the accuracy of FNAC in predicting positive axillary lymph nodes. METHODS: 161 patients with screen-detected invasive carcinoma and who had pre-operative FNAC of a radiologically abnormal axillary lymph node were identified from two screening units, The axillary FNAC reports were correlated with sentinel node biopsy and AC reports, and sensitivity, specificity, positive (PPV) and negative (NPV) predictive values were calculated. RESULTS: FNAC had a moderate sensitivity (66.3%) and NPV (71.8%), and a high specificity (98.7%) and PPV (98.3%). Most patients (86%) had a single axillary operation. The sensitivity was highest in grade 3 (81.8%) and ductal type (77.8%) tumours. The sensitivity was lower in tumours of special type (34.8%), grade 1 tumours (50%) and those without lymphovascular invasion (LVI) (55.9%). The NPV was highest in pT1 (86.7%) and in grade 1 (84.5%) tumours, and lowest (44%) in tumours with LVI. The PPV was 100% in grade 1 and 3 tumours, stage pT2 and pT3 tumours and those without LVI, and was high (>96%) in all other groups. In lymph-node-positive patients, the mean number of lymph nodes involved was higher in the case of a positive (6.4) than negative FNAC (4.4). CONCLUSIONS: FNAC of ultrasonically abnormal axillary lymph nodes achieved surgical staging by a single operation in most patients with screen-detected invasive breast carcinoma, with moderate sensitivity and high specificity.

  15. Development of an MRI/x-ray/ultrasound compatible marker for pre-operative breast tumour localization

    International Nuclear Information System (INIS)

    Li Yangmei; Wang, Jianxiong; Holloway, Claire; Plewes, Donald B

    2005-01-01

    This paper describes an in vitro investigation into the composition, structure and development of an magnetic resonance imaging (MRI), ultrasound (US) and x-ray imaging compatible marker for breast tumour localization. The marker is composed of 0.4-0.6 mm glass and iron-containing aluminium microspheres suspended in a gelatin matrix. The final form of the marker is a cylindrical shape 7 mm long with 2.05 mm diameter to facilitate delivery through a 12 gauge biopsy needle. To get optimal reflectivity for the US contrast, the glass microsphere concentration was found to be 40% by weight. US contrast is independent of marker orientation and the cylindrical shape made its US signal appearance distinctive thus ensuring confident identification. To control the MRI contrast, iron content was varied to generate a clear and local susceptibility signal void to reflect the marker position. Optimal iron content was found to be 52 μg iron which produced a clear signal void in spoiled gradient recalled MR images. The appearance of the susceptibility artefact is determined by the marker's shape, orientation and echo time. The final marker produces a dark artefact in MRI while appears as a clear hyperintense structure with acoustic shadowing in US images. The x-ray image showed the marker as a radio-opaque structure. This in vitro study demonstrates that the marker forms an alternative to traditional wire localization currently used for breast surgical procedures and creates new opportunities for US guided surgical procedures

  16. Does breast screening offer a survival benefit? A retrospective comparative study of oncological outcomes of screen-detected and symptomatic early stage breast cancer cases.

    Science.gov (United States)

    Újhelyi, M; Pukancsik, D; Kelemen, P; Kovács, E; Kenessey, I; Udvarhelyi, N; Bak, M; Kovács, T; Mátrai, Z

    2016-12-01

    Mammography screening reduces breast cancer mortality by up to 32%. However, some recent studies have questioned the impact of non-palpable breast cancer detection on mortality reduction. The aim of this study was to analyse the clinicopathological and long-term follow-up data of early stage screened and symptomatic breast cancer patients. The institutional prospectively led database was systematically analysed for breast cancer cases diagnosed via the mammography screening program from 2002 to 2009. As a control group, symptomatic early stage breast cancer patients were collected randomly from the same database and matched for age and follow-up period. All medical records were reviewed retrospectively. Data from 298 breast cancer patients were collected from 47,718 mammography screenings. In addition, 331 symptomatic breast cancer patients were randomly selected. The screened group presented a significantly lower median tumour size (P screened group (P screened group did not exhibit better overall (P = 0.717) or disease-free survival (P = 0.081) compared to the symptomatic group. Our results do not suggest that mammography screening does not reduce breast cancer mortality but the mammography screening did not bring any significant improvement in patient overall or disease-free survival for the early stage breast cancer patients compared to the symptomatic group. The drawback of symptomatic early stage tumours compared to non-palpable tumours could be equalized by modern multimodality oncology treatments. Copyright © 2016 Elsevier Ltd, BASO ~ the Association for Cancer Surgery, and the European Society of Surgical Oncology. All rights reserved.

  17. Reproductive hormones in breast cancer bone metastasis: The role of inhibins

    Directory of Open Access Journals (Sweden)

    Caroline Wilson

    2016-09-01

    Full Text Available The spread of breast cancer cells to bone and survival in this new metastatic environment is influenced not only by the genetic signature of the cells, but also multiple host cells and soluble factors produced locally (paracrine or from distant sites (endocrine. Disrupting this metastatic process has been evaluated in clinical trials of the bone targeted agents bisphosphonates and denosumab and have shown that these agents reduce the recurrence of breast cancer in postmenopausal women only, suggesting the efficacy of the drugs are influenced by levels of reproductive endocrine hormones. The molecular mechanism driving this differential effect has not been definitively identified, however, there is evidence that both reproductive hormones and bisphosphonates can affect similar paracrine factors and cellular components of the bone metastatic niche. This review focuses on how the ovarian endocrine hormone, inhibin, interacts with the paracrine factors activin and follistatin, abundant in the primary tumour and bone microenvironment, with subsequent effects on tumour cell survival. Inhibin also affects the cellular components of the bone microenvironment primarily the osteoblastic niche. Recent evidence has shown that bisphosphonates also alter this niche, which may represent a common mechanism by which inhibin and bisphosphonates interact to influence disease outcomes in early breast cancer. Further research is needed to fully elucidate these molecular mechanisms to enable understanding and future development of alternative bone targeted treatments with anti-tumour efficacy in premenopausal women.

  18. Frequent epigenetic inactivation of Wnt antagonist genes in breast cancer

    Science.gov (United States)

    Suzuki, H; Toyota, M; Caraway, H; Gabrielson, E; Ohmura, T; Fujikane, T; Nishikawa, N; Sogabe, Y; Nojima, M; Sonoda, T; Mori, M; Hirata, K; Imai, K; Shinomura, Y; Baylin, S B; Tokino, T

    2008-01-01

    Although mutation of APC or CTNNB1 (β-catenin) is rare in breast cancer, activation of Wnt signalling is nonetheless thought to play an important role in breast tumorigenesis, and epigenetic silencing of Wnt antagonist genes, including the secreted frizzled-related protein (SFRP) and Dickkopf (DKK) families, has been observed in various tumours. In breast cancer, frequent methylation and silencing of SFRP1 was recently documented; however, altered expression of other Wnt antagonist genes is largely unknown. In the present study, we found frequent methylation of SFRP family genes in breast cancer cell lines (SFRP1, 7 out of 11, 64%; SFRP2, 11 out of 11, 100%; SFRP5, 10 out of 11, 91%) and primary breast tumours (SFRP1, 31 out of 78, 40%; SFRP2, 60 out of 78, 77%; SFRP5, 55 out of 78, 71%). We also observed methylation of DKK1, although less frequently, in cell lines (3 out of 11, 27%) and primary tumours (15 out of 78, 19%). Breast cancer cell lines express various Wnt ligands, and overexpression of SFRPs inhibited cancer cell growth. In addition, overexpression of a β-catenin mutant and depletion of SFRP1 using small interfering RNA synergistically upregulated transcriptional activity of T-cell factor/lymphocyte enhancer factor. Our results confirm the frequent methylation and silencing of Wnt antagonist genes in breast cancer, and suggest that their loss of function contributes to activation of Wnt signalling in breast carcinogenesis. PMID:18283316

  19. Ultrasound guided pO2 measurement of breast cancer reoxygenation after neoadjuvant chemotherapy and hyperthermia treatment.

    Science.gov (United States)

    Vujaskovic, Z; Rosen, E L; Blackwell, K L; Jones, E L; Brizel, D M; Prosnitz, L R; Samulski, T V; Dewhirst, M W

    2003-01-01

    The objective of this study was to determine whether neoadjuvant chemotherapy in combination with hyperthermia (HT) would improve oxygenation in locally advanced breast tumours. The study describes a new optimized ultrasound guided technique of pO2 measurement using Eppendorf polarographic oxygen probes in 18 stage IIB-III breast cancer patients. Prior to treatment, tumour hypoxia (median pO2pO2=3.2 mmHg). Seven patients had well oxygenated tumours (median pO2 of 48.3 mmHg). Eight patients with hypoxic tumours prior to treatment had a significant improvement (p=0.0008) in tumour pO2 after treatment (pO2 increased to 19.2 mmHg). In three patients, tumours remained hypoxic (average median pO2=4.5 mmHg). The advantages of the ultrasound guided pO2 probe are in the accuracy of the Eppendorf electrode placement in tumour tissue, the ability to monitor electrode movement through the tumour tissue during the measurement and the ability to avoid electrode placement near or in large blood vessels by using colour Doppler imaging. The results of this preliminary study suggest that the combination of neoadjuvant chemotherapy and hyperthermia improves oxygenation in locally advanced breast tumours that are initially hypoxic.

  20. Factors associated with the non detection of the sentinel node in breast cancer

    Energy Technology Data Exchange (ETDEWEB)

    Guirao, Sara; Benitez Segura, Ana; Bajen, Maria Tereza; Brulles, Ynonet Ricart; Mora Salvado, Jaume; Vilardell, Ana Domenech; Rodriguez Gassen, Alba; Roca Engronyat, Manel; Puchal Ane, Rafael; Martin-Comin, Josep [Hospital Universitario de Bellvitge-IDIBELL (Spain). S. Medicina Nuclear; Hospitalet de Llobregat (Spain)]. E-mail: jmartincomin@csub.scs.es

    2005-10-15

    The aim of the work was to analyse the potential influence of different factors on the surgical detection of sentinel lymph node in breast cancer. The procedure has been performed in 704 patients. In 43 out of the 704 cases, the SN was not detected, 24 were palpable and 19 had no palpable tumors. Lymphoscintigraphy was done in 2 h p.i. of 37-55 MBq of 99m Tc-nanocolloid. The day before surgery in palpable tumours and 4 h previous to surgery in non-palpable tumours, surgical detection was performed using a gamma probe. The following factors were analysed: patient age, tumour size, breast quadrant tumour localization, scintigraphic visualization,n and the palpation of the tumour. Results: Patient age was significantly (p<0.001) higher in the patients in whom SN was not detected. Scintigraphic visualization was significantly (p<0.05) lower in the patients in whom SN was not detected. There were no significant differences concerning the other parameters analysed. Conclusion: patient age and scintigraphic visualization are parameters that directly influence the detection of sentinel node in breast cancer.(author)

  1. Using Breast Cancer Risk Associated Polymorphisms to Identify Women for Breast Cancer Chemoprevention.

    Directory of Open Access Journals (Sweden)

    Elad Ziv

    Full Text Available Breast cancer can be prevented with selective estrogen receptor modifiers (SERMs and aromatase inhibitors (AIs. The US Preventive Services Task Force recommends that women with a 5-year breast cancer risk ≥3% consider chemoprevention for breast cancer. More than 70 single nucleotide polymorphisms (SNPs have been associated with breast cancer. We sought to determine how to best integrate risk information from SNPs with other risk factors to risk stratify women for chemoprevention.We used the risk distribution among women ages 35-69 estimated by the Breast Cancer Surveillance Consortium (BCSC risk model. We modeled the effect of adding 70 SNPs to the BCSC model and examined how this would affect how many women are reclassified above and below the threshold for chemoprevention.We found that most of the benefit of SNP testing a population is achieved by testing a modest fraction of the population. For example, if women with a 5-year BCSC risk of >2.0% are tested (~21% of all women, ~75% of the benefit of testing all women (shifting women above or below 3% 5-year risk would be derived. If women with a 5-year risk of >1.5% are tested (~36% of all women, ~90% of the benefit of testing all women would be derived.SNP testing is effective for reclassification of women for chemoprevention, but is unlikely to reclassify women with <1.5% 5-year risk. These results can be used to implement an efficient two-step testing approach to identify high risk women who may benefit from chemoprevention.

  2. Tumour and tumour-like lesions of the patella - a multicentre experience

    International Nuclear Information System (INIS)

    Singh, J.; James, S.L.; Davies, A.M.; Kroon, H.M.; Woertler, K.; Anderson, S.E.

    2009-01-01

    Fifty-nine cases of lesions presenting in the patella were identified after review of the databases of four European bone tumour registries. Of the 59 cases, 46% were non neoplastic, 39% were benign and 15% were malignant. The commonest benign neoplasm was giant cell tumour (GCT) (11 cases). Younger patients were more likely to have a benign neoplasm. Lesions in patients less than 40 years of age included giant cell tumour, chondroblastoma, aneurysmal bone cyst (ABC), osteomyelitis, osteoid osteoma and solitary bone cyst. In patients older than 40 years, the following were common lesions: intra-osseous gout, metastasis and intra-osseous ganglion. Expansion of the patella with thinning of cortex was seen more commonly in GCT and brown tumour in hyperparathyroidism. There was associated soft tissue extension in gout and malignant lesions. (orig.)

  3. Tumour and tumour-like lesions of the patella - a multicentre experience

    Energy Technology Data Exchange (ETDEWEB)

    Singh, J.; James, S.L.; Davies, A.M. [The Royal Orthopaedic Hospital, Department of Radiology, Birmingham (United Kingdom); Kroon, H.M. [Leiden University Medical Centre, Department of Radiology, C-2-S, P. O Box 9600, Leiden (Netherlands); Woertler, K. [Technische Universitaet Muenchen, Department of Radiology, Munich (Germany); Anderson, S.E. [Knochentumor- Referenzzentrum der Schweizerischen Gesellschaft fuer Pathologie, Basel (Switzerland)

    2009-03-15

    Fifty-nine cases of lesions presenting in the patella were identified after review of the databases of four European bone tumour registries. Of the 59 cases, 46% were non neoplastic, 39% were benign and 15% were malignant. The commonest benign neoplasm was giant cell tumour (GCT) (11 cases). Younger patients were more likely to have a benign neoplasm. Lesions in patients less than 40 years of age included giant cell tumour, chondroblastoma, aneurysmal bone cyst (ABC), osteomyelitis, osteoid osteoma and solitary bone cyst. In patients older than 40 years, the following were common lesions: intra-osseous gout, metastasis and intra-osseous ganglion. Expansion of the patella with thinning of cortex was seen more commonly in GCT and brown tumour in hyperparathyroidism. There was associated soft tissue extension in gout and malignant lesions. (orig.)

  4. [Occurrence of associated tumours in chronic lymphocytic leukemia].

    Science.gov (United States)

    Szerafin, László; Jakó, János; Varju, Lóránt

    2016-10-01

    Chronic lymphocytic leukemia is one of the most common hematologic malignancy. The aim of the authors was to investigate the characteristics of malignancies associated with chronic lymphocytic leukemia in patients diagnozed between 2000 and 2015. Data of patients with chronic lymphocytic leukemia who had other associated tumours were analysed using the Leukemia/Lymphoma Registry of the Szabolcs-Szatmár-Bereg County, Hungary and patient records. Between January 1, 2000 and December 31, 2015, 526 patients with chronic lymphocytic leukemia were diagnosed. 95 patients of the 526 patients (18.06%) were diagnosed as having associated other tumours. In 48/95 patients (50.5%) the first diagnosed tumour was chronic lymphocytic leukemia, in 23/95 patients (24.2%) the first recognized malignancy was the associated tumour, whereas in 24/95 patients (25.3%) synchron tumours were diagnosed. The number of patients with more than one associated tumour was 10/95 (10.5%). The total number of tumours was 107. The incidence of chronic lymphoid leukemia increased in the period between 2000 and 2015 as compared to the period between 1983 and 1999 (3.19 vs 5.65/100 000 person/year). The occurrence of associated malignancies increased as well (8.06% vs 18.06%). In addition to the most common tumours (colorectal, breast, lung, prostate), skin squamous cell carcinoma (17/95 patients; 17.9%) and melanoma (6/95 patients; 6.3%) also frequently occurred. The second malignancies were most frequently discovered after the diagnosis of chronic lymphocytic leukemia and synchron tumours accounting for 78.5% (84/107) of all associated tumours. The incidence of second malignancies decreased 10 years after the diagnosis of chronic lymphocytic leukemia. The possible reasons for the high frequency of other tumours associated with chronic lymphocytic leukemia are elderly age of patients, immunsuppressed state and, presumably, chemotherapy of patients with chronic lymphocytic leukemia. During the follow up

  5. Gene expression variation to predict 10-year survival in lymph-node-negative breast cancer

    International Nuclear Information System (INIS)

    Karlsson, Elin; Delle, Ulla; Danielsson, Anna; Olsson, Björn; Abel, Frida; Karlsson, Per; Helou, Khalil

    2008-01-01

    It is of great significance to find better markers to correctly distinguish between high-risk and low-risk breast cancer patients since the majority of breast cancer cases are at present being overtreated. 46 tumours from node-negative breast cancer patients were studied with gene expression microarrays. A t-test was carried out in order to find a set of genes where the expression might predict clinical outcome. Two classifiers were used for evaluation of the gene lists, a correlation-based classifier and a Voting Features Interval (VFI) classifier. We then evaluated the predictive accuracy of this expression signature on tumour sets from two similar studies on lymph-node negative patients. They had both developed gene expression signatures superior to current methods in classifying node-negative breast tumours. These two signatures were also tested on our material. A list of 51 genes whose expression profiles could predict clinical outcome with high accuracy in our material (96% or 89% accuracy in cross-validation, depending on type of classifier) was developed. When tested on two independent data sets, the expression signature based on the 51 identified genes had good predictive qualities in one of the data sets (74% accuracy), whereas their predictive value on the other data set were poor, presumably due to the fact that only 23 of the 51 genes were found in that material. We also found that previously developed expression signatures could predict clinical outcome well to moderately well in our material (72% and 61%, respectively). The list of 51 genes derived in this study might have potential for clinical utility as a prognostic gene set, and may include candidate genes of potential relevance for clinical outcome in breast cancer. According to the predictions by this expression signature, 30 of the 46 patients may have benefited from different adjuvant treatment than they recieved. The research on these tumours was approved by the Medical Faculty Research

  6. Patient selection for accelerated partial-breast irradiation (APBI) after breast-conserving surgery: Recommendations of the Groupe Europeen de Curietherapie-European Society for Therapeutic Radiology and Oncology (GEC-ESTRO) breast cancer working group based on clinical evidence (2009)

    International Nuclear Information System (INIS)

    Polgar, Csaba; Limbergen, Erik Van; Poetter, Richard; Kovacs, Gyoergy; Polo, Alfredo; Lyczek, Jaroslaw; Hildebrandt, Guido; Niehoff, Peter; Guinot, Jose Luis; Guedea, Ferran; Johansson, Bengt; Ott, Oliver J.; Major, Tibor; Strnad, Vratislav

    2010-01-01

    Purpose: To give recommendations on patient selection criteria for the use of accelerated partial-breast irradiation (APBI) based on available clinical evidence complemented by expert opinion. Methods and materials: Overall, 340 articles were identified by a systematic search of the PubMed database using the keywords 'partial-breast irradiation' and 'APBI'. This search was complemented by searches of reference lists of articles and handsearching of relevant conference abstracts and book chapters. Of these, 3 randomized and 19 prospective non-randomized studies with a minimum median follow-up time of 4 years were identified. The authors reviewed the published clinical evidence on APBI, complemented by relevant clinical and pathological studies of standard breast-conserving therapy and, through a series of personal communications, formulated the recommendations presented in this article. Results: The GEC-ESTRO Breast Cancer Working Group recommends three categories guiding patient selection for APBI: (1) a low-risk group for whom APBI outside the context of a clinical trial is an acceptable treatment option; including patients ageing at least 50 years with unicentric, unifocal, pT1-2 (≤30 mm) pN0, non-lobular invasive breast cancer without the presence of an extensive intraductal component (EIC) and lympho-vascular invasion (LVI) and with negative surgical margins of at least 2 mm, (2) a high-risk group, for whom APBI is considered contraindicated; including patients ageing ≤40 years; having positive margins, and/or multicentric or large (>30 mm) tumours, and/or EIC positive or LVI positive tumours, and/or 4 or more positive lymph nodes or unknown axillary status (pNx), and (3) an intermediate-risk group, for whom APBI is considered acceptable only in the context of prospective clinical trials. Conclusions: These recommendations will provide a clinical guidance regarding the use of APBI outside the context of a clinical trial before large-scale randomized

  7. Irradiation specifically sensitises solid tumour cell lines to TRAIL mediated apoptosis

    International Nuclear Information System (INIS)

    Marini, Patrizia; Schmid, Angelika; Jendrossek, Verena; Faltin, Heidrun; Daniel, Peter T; Budach, Wilfried; Belka, Claus

    2005-01-01

    TRAIL (tumor necrosis factor related apoptosis inducing ligand) is an apoptosis inducing ligand with high specificity for malignant cell systems. Combined treatment modalities using TRAIL and cytotoxic drugs revealed highly additive effects in different tumour cell lines. Little is known about the efficacy and underlying mechanistic effects of a combined therapy using TRAIL and ionising radiation in solid tumour cell systems. Additionally, little is known about the effect of TRAIL combined with radiation on normal tissues. Tumour cell systems derived from breast- (MDA MB231), lung- (NCI H460) colorectal- (Colo 205, HCT-15) and head and neck cancer (FaDu, SCC-4) were treated with a combination of TRAIL and irradiation using two different time schedules. Normal tissue cultures from breast, prostate, renal and bronchial epithelia, small muscle cells, endothelial cells, hepatocytes and fibroblasts were tested accordingly. Apoptosis was determined by fluorescence microscopy and western blot determination of PARP processing. Upregulation of death receptors was quantified by flow cytometry. The combined treatment of TRAIL with irradiation strongly increased apoptosis induction in all treated tumour cell lines compared to treatment with TRAIL or irradiation alone. The synergistic effect was most prominent after sequential application of TRAIL after irradiation. Upregulation of TRAIL receptor DR5 after irradiation was observed in four of six tumour cell lines but did not correlate to tumour cell sensitisation to TRAIL. TRAIL did not show toxicity in normal tissue cell systems. In addition, pre-irradiation did not sensitise all nine tested human normal tissue cell cultures to TRAIL. Based on the in vitro data, TRAIL represents a very promising candidate for combination with radiotherapy. Sequential application of ionising radiation followed by TRAIL is associated with an synergistic induction of cell death in a large panel of solid tumour cell lines. However, TRAIL receptor

  8. Feasibility of magnetic marker localisation for non-palpable breast cancer

    NARCIS (Netherlands)

    Schermers, B.; van der Hage, Jos A.; Loo, C.E.; Vrancken Peeters, M.T.F.D.; Winter-Warnars, H. A.O.; Duijnhoven, F.H.; ten Haken, B.; Muller, S.H.; Ruers, T. J.M.

    2017-01-01

    Objectives Accurate tumour localisation is essential for breast-conserving surgery of non-palpable tumours. Current localisation technologies are associated with disadvantages such as logistical challenges and migration issues (wire guided localisation) or legislative complexities and high

  9. A priori Prediction of Neoadjuvant Chemotherapy Response and Survival in Breast Cancer Patients using Quantitative Ultrasound.

    Science.gov (United States)

    Tadayyon, Hadi; Sannachi, Lakshmanan; Gangeh, Mehrdad J; Kim, Christina; Ghandi, Sonal; Trudeau, Maureen; Pritchard, Kathleen; Tran, William T; Slodkowska, Elzbieta; Sadeghi-Naini, Ali; Czarnota, Gregory J

    2017-04-12

    Quantitative ultrasound (QUS) can probe tissue structure and analyze tumour characteristics. Using a 6-MHz ultrasound system, radiofrequency data were acquired from 56 locally advanced breast cancer patients prior to their neoadjuvant chemotherapy (NAC) and QUS texture features were computed from regions of interest in tumour cores and their margins as potential predictive and prognostic indicators. Breast tumour molecular features were also collected and used for analysis. A multiparametric QUS model was constructed, which demonstrated a response prediction accuracy of 88% and ability to predict patient 5-year survival rates (p = 0.01). QUS features demonstrated superior performance in comparison to molecular markers and the combination of QUS and molecular markers did not improve response prediction. This study demonstrates, for the first time, that non-invasive QUS features in the core and margin of breast tumours can indicate breast cancer response to neoadjuvant chemotherapy (NAC) and predict five-year recurrence-free survival.

  10. Prevalence of mucosal and cutaneous human papillomavirus in Moroccan breast cancer

    Directory of Open Access Journals (Sweden)

    Amal ElAmrani

    2018-06-01

    Full Text Available Background: Due to recent technical improvements and some encouraging new results, there has been a resurgence of interest in the possibility that a substantial proportion of breast cancers (BCs may be caused by viral infections, including Human papillomavirus (HPV. The aim of this study was to determine the prevalence of mucosal and cutaneous HPV in tumours from Moroccan BC patients. Materials and methods: Frozen tumours from 76 BC cases and 12 controls were evaluated for the presence of 62 HPV-types using highly sensitive assays that combine multiplex polymerase chain reaction and bead-based Luminex technology. Results: HPV DNA was found in 25.0% of BC tumours and only 8.3% of controls. Beta and gamma HPV types were found in 10.5% and 6.6% of BC tumours, respectively. High-risk mucosal types HPV16 and 18 were not detected in the subjects, but other probable/possible high-risk or high-risk -HPV types (HPV51, 52, 58, 59, and 66 were found in 5.3% of BC tumours. Statistical analysis showed no significant difference between, controls, BC cases and the inflammatory status (p > 0.05. Conclusion: HPV DNA was found 3 times as frequently in the BC tumours as in the controls. However, this difference requires confirmation in a larger sample. Keywords: Breast cancer, Human papillomavirus, Inflammatory breast cancer, Type-specific multiplex genotyping, Morocco

  11. 18F-FDG uptake in breast cancer correlates with immunohistochemically defined subtypes

    International Nuclear Information System (INIS)

    Koo, Hye Ryoung; Park, Jeong Seon; Kang, Keon Wook; Cho, Nariya; Chang, Jung Min; Bae, Min Sun; Kim, Won Hwa; Lee, Su Hyun; Seo, Mirinae; Moon, Woo Kyung; Kim, Mi Young; Kim, Jin You

    2014-01-01

    To determine whether a correlation exists between maximum standardized uptake value (SUV max ) on 18 F-fluorodeoxyglucose positron emission tomography (FDG-PET) and the subtypes of breast cancer. This retrospective study involved 548 patients (mean age 51.6 years, range 21-81 years) with 552 index breast cancers (mean size 2.57 cm, range 1.0-14.5 cm). The correlation between 18 F-FDG uptake in PET/CT, expressed as SUV max , and immunohistochemically defined subtypes (luminal A, luminal B, human epidermal growth factor receptor 2 (HER2) positive and triple negative) was analyzed. The mean SUV max value of the 552 tumours was 6.07 ± 4.63 (range 0.9-32.8). The subtypes of the 552 tumours were 334 (60 %) luminal A, 66 (12 %) luminal B, 60 (11 %) HER2 positive and 92 (17 %) triple negative, for which the mean SUV max values were 4.69 ± 3.45, 6.51 ± 4.18, 7.44 ± 4.73 and 9.83 ± 6.03, respectively. In a multivariate regression analysis, triple-negative and HER2-positive tumours had 1.67-fold (P max values, respectively, than luminal A tumours after adjustment for invasive tumour size, lymph node involvement status and histologic grade. FDG uptake was independently associated with subtypes of invasive breast cancer. Triple-negative and HER2-positive breast cancers showed higher SUV max values than luminal A tumours. circle 18 F-FDG PET demonstrates increased tissue glucose metabolism, a hallmark of cancers. (orig.)

  12. Sentinel Lymph Node Biopsy in Breast Cancer: Predictors of Axillary and Non-Sentinel Lymph Node Involvement

    Directory of Open Access Journals (Sweden)

    Hakan Postacı

    2013-12-01

    Full Text Available Background: Sentinel lymph node biopsy is a standard method for the evaluation of axillary status in patients with T1-2N0M0 breast cancers. Aims: To determine the prognostic significance of primary tumour-related clinico-histopathological factors on axillary and non-sentinel lymph node involvement of patients who underwent sentinel lymph node biopsy. Study design: Retrospective clinical study. Methods: In the present study, 157 sentinel lymph node biopsies were performed in 151 consecutive patients with early stage breast cancer between June 2008 and December 2011. Results: Successful lymphatic mapping was obtained in 157 of 158 procedures (99.4%. The incidence of larger tumour size (2.543±1.21 vs. 1.974±1.04, lymphatic vessel invasion (70.6% vs. 29.4%, blood vessel invasion (84.2% vs. 15.8%, and invasive lobular carcinoma subtype (72.7% vs. 27.3% were statistically significantly higher in patients with positive SLNs. Logistic stepwise regression analysis disclosed tumour size (odds ratio: 1.51, p=0.0021 and lymphatic vessel invasion (odds ratio: 4.68, p=0.001 as significant primary tumour-related prognostic determinants of SLN metastasis. Conclusion: A close relationship was identified between tumour size and lymphatic vessel invasion of the primary tumour and axillary lymph node involvement. However, the positive predictive value of these two independent variables is low and there is no compelling evidence to recommend their use in routine clinical practice.

  13. Immunological Characterization of Whole Tumour Lysate-Loaded Dendritic Cells for Cancer Immunotherapy

    Science.gov (United States)

    Ottobrini, Luisa; Biasin, Mara; Borelli, Manuela; Lucignani, Giovanni; Trabattoni, Daria; Clerici, Mario

    2016-01-01

    Introduction Dendritic cells play a key role as initiators of T-cell responses, and even if tumour antigen-loaded dendritic cells can induce anti-tumour responses, their efficacy has been questioned, suggesting a need to enhance immunization strategies. Matherials & Methods We focused on the characterization of bone marrow-derived dendritic cells pulsed with whole tumour lysate (TAA-DC), as a source of known and unknown antigens, in a mouse model of breast cancer (MMTV-Ras). Dendritic cells were evaluated for antigen uptake and for the expression of MHC class I/II and costimulatory molecules and markers associated with maturation. Results Results showed that antigen-loaded dendritic cells are characterized by a phenotypically semi-mature/mature profile and by the upregulation of genes involved in antigen presentation and T-cell priming. Activated dendritic cells stimulated T-cell proliferation and induced the production of high concentrations of IL-12p70 and IFN-γ but only low levels of IL-10, indicating their ability to elicit a TH1-immune response. Furthermore, administration of Antigen loaded-Dendritic Cells in MMTV-Ras mice evoked a strong anti-tumour response in vivo as demonstrated by a general activation of immunocompetent cells and the release of TH1 cytokines. Conclusion Data herein could be useful in the design of antitumoral DC-based therapies, showing a specific activation of immune system against breast cancer. PMID:26795765

  14. Prognostic value of metabolic tumour volume and total lesion glycolysis in 18F-FDG PET/CT scans in locally advanced breast cancer staging.

    Science.gov (United States)

    Jiménez-Ballvé, A; García García-Esquinas, M; Salsidua-Arroyo, O; Serrano-Palacio, A; García-Sáenz, J A; Ortega Candil, A; Fuentes Ferrer, M E; Rodríguez Rey, C; Román-Santamaría, J M; Moreno, F; Carreras-Delgado, J L

    To determine whether metabolic tumour volume (MTV) and total lesion glycolysis (TLG) are able to predict recurrence risk in locally advanced breast cancer (LABC) patients. Retrospective study of LABC patients who undertook neoadjuvant, local and adjuvant treatment and follow up. A 18 F-FDG PET/CT study for initial staging was performed analysing in this study different metabolic parameters (MTV, TLG, SUVmax and SUVmed) both in the primary tumour (T) as well as in axillary nodes (N) and whole-body (WB). Forty females were included between January 2010-2011; follow up until January 2015 was completed. The average follow-up was 46 months. Twenty percent presented recurrence: local disease (n=2) and distant metastasis (n=6); 3 patients died (38% of the patients which recurred and 7.5% from the total). SUVmax, MTV and TLG, in T, N and WB, were higher in those patients with recurrence. The MTV and TLG parameters in the tumour (T) were related to the recurrence rate (P=.020 and P=.028, respectively); whereas SUVmax in the lymph nodes (N) was significantly related (P=.008) to the recurrence rate. The best cut-off points to predict recurrence where: MTV T ≥19.3cm 3 , TLG T≥74.4g and SUVmax N≥13.8, being 10-12 times more likely to recidivate when these thresholds where exceeded. Tumour grade was the only clinical-pathological variable which was related to recurrence probability (p=.035). In this study of LABC patients the metabolic parameters which have a better relationship with recurrence rate are: MTV and TLG in the primary tumour, SUVmax in the regional lymph node disease and whole-body PET data. Copyright © 2016 Elsevier España, S.L.U. y SEMNIM. All rights reserved.

  15. Metastatic Breast Cancer and Hormonal Receptor Status among a ...

    African Journals Online (AJOL)

    The ANNALS of AFRICAN SURGERY | www.sskenya.org. The ANNALS of ... metastatic lesions and survival among breast cancer patients. ... year survival rate (2). Breast ... Three core ... ER negative and 35 (49.3%) had PR positive tumours.

  16. Molecular pathology of bone tumours: diagnostic implications.

    Science.gov (United States)

    Puls, Florian; Niblett, Angela J; Mangham, D Chas

    2014-03-01

    Alongside histomorphology and immunohistochemistry, molecular pathology is now established as one of the cornerstones in the tissue diagnosis of bone tumours. We describe the principal molecular pathological techniques employed, and each of the bone tumour entities where their identified characteristic molecular pathological changes can be detected to support and confirm the suspected histological diagnosis. Tumours discussed include fibrous dysplasia, classical and subtype osteosarcomas, central and surface cartilaginous tumours, Ewing's sarcoma, vascular tumours, aneurysmal bone cyst, chordoma, myoepithelioma, and angiomatoid fibrous histiocytoma. This is a rapidly evolving field with discoveries occurring every few months, and some of the newer entities (the Ewing's-like sarcomas), which are principally identified by their molecular pathology characteristics, are discussed. © 2013 John Wiley & Sons Ltd.

  17. Cancer of the accessory breast - a case report

    International Nuclear Information System (INIS)

    Madej, B.; Balak, B.; Winkler, I.; Burdan, F.

    2009-01-01

    Breast neoplasm may develop in ectopically located glandular tissue. This paper presents an interesting and rare case of a 50-year-old female who despite regular mammography screening examination developed an invasive accessory breast cancer. Clinical examination revealed a 2 cm - tumour localized 4 cm below the left infra mammary fold. The lesion was immobile, the skin and the atrophic nipple were retracted, the tumour infiltrated the thoracic wall. Oligo biopsy and additional examinations showed an invasive stage IIIB ductal breast cancer (Bloom II, G-2). The receptor status was: ER(+), PGR(+), HER2(-). The increased level of cancer antigen 15.3 was found. The patient was submitted to pre-operative chemotherapy. She also underwent surgery and subsequently post-operative chemotherapy and radiotherapy. On the basis of the presented case, it could be concluded that the accessory mammary glands are out of the image of screening breast examinations. Accessory breast cancer is usually diagnosed by clinical examination and ultrasonography. Preventive resection of accessory breast in women at high risk of developing breast cancer can be considered as the treatment of choice in most patients. (authors)

  18. Accelerated partial breast irradiation using intensity-modulated radiotherapy versus whole breast irradiation: 5-year survival analysis of a phase 3 randomised controlled trial.

    Science.gov (United States)

    Livi, Lorenzo; Meattini, Icro; Marrazzo, Livia; Simontacchi, Gabriele; Pallotta, Stefania; Saieva, Calogero; Paiar, Fabiola; Scotti, Vieri; De Luca Cardillo, Carla; Bastiani, Paolo; Orzalesi, Lorenzo; Casella, Donato; Sanchez, Luis; Nori, Jacopo; Fambrini, Massimiliano; Bianchi, Simonetta

    2015-03-01

    Accelerated partial breast irradiation (APBI) has been introduced as an alternative treatment method for selected patients with early stage breast cancer (BC). Intensity-modulated radiotherapy (IMRT) has the theoretical advantage of a further increase in dose conformity compared with three-dimensional techniques, with more normal tissue sparing. The aim of this randomised trial is to compare the local recurrence and survival of APBI using the IMRT technique after breast-conserving surgery to conventional whole-breast irradiation (WBI) in early stage BC. This study was performed at the University of Florence (Florence, Italy). Women aged more than 40years affected by early BC, with a maximum pathological tumour size of 25mm, were randomly assigned in a 1:1 ratio to receive either WBI or APBI using IMRT. Patients in the APBI arm received a total dose of 30 Gy to the tumour bed in five daily fractions. The WBI arm received 50Gy in 25 fractions, followed by a boost on the tumour bed of 10Gy in five fractions. The primary end-point was occurrence of ipsilateral breast tumour recurrences (IBTRs); the main analysis was by intention-to-treat. This trial is registered with ClinicalTrials.gov, number NCT02104895. A total of 520 patients were randomised (260 to external WBI and 260 to APBI with IMRT) between March 2005 and June 2013. At a median follow-up of 5.0 years (Interquartile Range (IQR) 3.4-7.0), the IBTR rate was 1.5% (three cases) in the APBI group (95% confidence interval (CI) 0.1-3.0) and in the WBI group (three cases; 95% CI 0.0-2.8). No significant difference emerged between the two groups (log rank test p=0.86). We identified seven deaths in the WBI group and only one in the APBI group (p=0.057). The 5-year overall survival was 96.6% for the WBI group and 99.4% for the APBI group. The APBI group presented significantly better results considering acute (p=0.0001), late (p=0.004), and cosmetic outcome (p=0.045). To our knowledge, this is the first randomised

  19. Skeletal muscle metastases: primary tumours, prevalence, and radiological features

    International Nuclear Information System (INIS)

    Surov, Alexey; Spielmann, Rolf Peter; Behrmann, Curd; Hainz, Michael; Holzhausen, Hans-Juergen; Arnold, Dirk; Katzer, Michaela; Schmidt, Joerg

    2010-01-01

    Although skeletal muscles comprise nearly 50% of the total human body mass and are well vascularised, metastases in the musculature are rare. The reported prevalence of skeletal muscle metastases from post-mortem studies of patients with cancer is inconstant and ranges from 0.03 to 17.5%. Of 5,170 patients with metastasised cancer examined and treated at our institution during the period from January 2000 to December 2007, 61 patients with muscle metastases (80 lesions) were identified on computed tomography (CT). Genital tumours (24.6%) were the most frequent malignancies metastasising into the skeletal musculature, followed by gastrointestinal tumours (21.3%), urological tumours (16.4%), and malignant melanoma (13.1%). Other primary malignancies were rarer, including bronchial carcinoma (8.2%), thyroid gland carcinoma (4.9%), and breast carcinoma (3.3%). In 8.2%, carcinoma of unknown primary was diagnosed. Skeletal muscle metastases (SMM) were located in the iliopsoas muscle (27.5%), paravertebral muscles (25%), gluteal muscles (16.3%), lower extremity muscles (12.5%), abdominal wall muscles (10%), thoracic wall muscles (5%), and upper extremity muscles (3.8%). Most (76.3%) of the 80 SMM were diagnosed incidentally during routine staging CT examinations, while 23.7% were symptomatic. Radiologically, SMM presented with five different types of lesions: focal intramuscular masses (type I, 52.5% of SMM), abscess-like intramuscular lesions (type II, 32.5%), diffuse metastatic muscle infiltration (type III, 8.8%), multifocal intramuscular calcification (type IV, 3.7%) and intramuscular bleeding (type V, 2.5%). (orig.)

  20. Skeletal muscle metastases: primary tumours, prevalence, and radiological features

    Energy Technology Data Exchange (ETDEWEB)

    Surov, Alexey; Spielmann, Rolf Peter; Behrmann, Curd [Martin-Luther-University Halle-Wittenberg, Department of Radiology, Halle (Germany); Hainz, Michael; Holzhausen, Hans-Juergen [Martin-Luther-University Halle-Wittenberg, Department of Pathology, Halle (Germany); Arnold, Dirk [Martin-Luther-University Halle-Wittenberg, Department of Haematology/Oncology, Halle (Germany); Katzer, Michaela [Martin-Luther-University Halle-Wittenberg, Department of Urology, Halle (Germany); Schmidt, Joerg [Martin-Luther-University Halle-Wittenberg, Department of Medical Statistics and Controlling, Halle (Germany)

    2010-03-15

    Although skeletal muscles comprise nearly 50% of the total human body mass and are well vascularised, metastases in the musculature are rare. The reported prevalence of skeletal muscle metastases from post-mortem studies of patients with cancer is inconstant and ranges from 0.03 to 17.5%. Of 5,170 patients with metastasised cancer examined and treated at our institution during the period from January 2000 to December 2007, 61 patients with muscle metastases (80 lesions) were identified on computed tomography (CT). Genital tumours (24.6%) were the most frequent malignancies metastasising into the skeletal musculature, followed by gastrointestinal tumours (21.3%), urological tumours (16.4%), and malignant melanoma (13.1%). Other primary malignancies were rarer, including bronchial carcinoma (8.2%), thyroid gland carcinoma (4.9%), and breast carcinoma (3.3%). In 8.2%, carcinoma of unknown primary was diagnosed. Skeletal muscle metastases (SMM) were located in the iliopsoas muscle (27.5%), paravertebral muscles (25%), gluteal muscles (16.3%), lower extremity muscles (12.5%), abdominal wall muscles (10%), thoracic wall muscles (5%), and upper extremity muscles (3.8%). Most (76.3%) of the 80 SMM were diagnosed incidentally during routine staging CT examinations, while 23.7% were symptomatic. Radiologically, SMM presented with five different types of lesions: focal intramuscular masses (type I, 52.5% of SMM), abscess-like intramuscular lesions (type II, 32.5%), diffuse metastatic muscle infiltration (type III, 8.8%), multifocal intramuscular calcification (type IV, 3.7%) and intramuscular bleeding (type V, 2.5%). (orig.)

  1. Large-scale genotyping identifies 41 new loci associated with breast cancer risk

    DEFF Research Database (Denmark)

    Michailidou, Kyriaki; Hall, Per; Gonzalez-Neira, Anna

    2013-01-01

    Breast cancer is the most common cancer among women. Common variants at 27 loci have been identified as associated with susceptibility to breast cancer, and these account for ∼9% of the familial risk of the disease. We report here a meta-analysis of 9 genome-wide association studies, including 10...

  2. Large-scale genotyping identifies 41 new loci associated with breast cancer risk

    NARCIS (Netherlands)

    Michailidou, Kyriaki; Hall, Per; Gonzalez-Neira, Anna; Ghoussaini, Maya; Dennis, Joe; Milne, Roger L.; Schmidt, Marjanka K.; Chang-Claude, Jenny; Bojesen, Stig E.; Bolla, Manjeet K.; Wang, Qin; Dicks, Ed; Lee, Andrew; Turnbull, Clare; Rahman, Nazneen; Fletcher, Olivia; Peto, Julian; Gibson, Lorna; dos Santos Silva, Isabel; Nevanlinna, Heli; Muranen, Taru A.; Aittomäki, Kristiina; Blomqvist, Carl; Czene, Kamila; Irwanto, Astrid; Liu, Jianjun; Waisfisz, Quinten; Meijers-Heijboer, Hanne; Adank, Muriel; van der Luijt, Rob B.; Hein, Rebecca; Dahmen, Norbert; Beckman, Lars; Meindl, Alfons; Schmutzler, Rita K.; Müller-Myhsok, Bertram; Lichtner, Peter; Hopper, John L.; Southey, Melissa C.; Makalic, Enes; Schmidt, Daniel F.; Uitterlinden, Andre G.; Hofman, Albert; Hunter, David J.; Chanock, Stephen J.; Vincent, Daniel; Bacot, François; Tessier, Daniel C.; Canisius, Sander; Wessels, Lodewyk F. A.; Haiman, Christopher A.; Shah, Mitul; Luben, Robert; Brown, Judith; Luccarini, Craig; Schoof, Nils; Humphreys, Keith; Li, Jingmei; Nordestgaard, Børge G.; Nielsen, Sune F.; Flyger, Henrik; Couch, Fergus J.; Wang, Xianshu; Vachon, Celine; Stevens, Kristen N.; Lambrechts, Diether; Moisse, Matthieu; Paridaens, Robert; Christiaens, Marie-Rose; Rudolph, Anja; Nickels, Stefan; Flesch-Janys, Dieter; Johnson, Nichola; Aitken, Zoe; Aaltonen, Kirsimari; Heikkinen, Tuomas; Broeks, Annegien; van 't Veer, Laura J.; van der Schoot, C. Ellen; Guénel, Pascal; Truong, Thérèse; Laurent-Puig, Pierre; Menegaux, Florence; Marme, Frederik; Schneeweiss, Andreas; Sohn, Christof; Burwinkel, Barbara; Zamora, M. Pilar; Perez, Jose Ignacio Arias; Pita, Guillermo; Alonso, M. Rosario; Cox, Angela; Brock, Ian W.; Cross, Simon S.; Reed, Malcolm W. R.; Sawyer, Elinor J.; Tomlinson, Ian; Kerin, Michael J.; Miller, Nicola; Henderson, Brian E.; Schumacher, Fredrick; Le Marchand, Loic; Andrulis, Irene L.; Knight, Julia A.; Glendon, Gord; Mulligan, Anna Marie; Lindblom, Annika; Margolin, Sara; Hooning, Maartje J.; Hollestelle, Antoinette; van den Ouweland, Ans M. W.; Jager, Agnes; Bui, Quang M.; Stone, Jennifer; Dite, Gillian S.; Apicella, Carmel; Tsimiklis, Helen; Giles, Graham G.; Severi, Gianluca; Baglietto, Laura; Fasching, Peter A.; Haeberle, Lothar; Ekici, Arif B.; Beckmann, Matthias W.; Brenner, Hermann; Müller, Heiko; Arndt, Volker; Stegmaier, Christa; Swerdlow, Anthony; Ashworth, Alan; Orr, Nick; Jones, Michael; Figueroa, Jonine; Lissowska, Jolanta; Brinton, Louise; Goldberg, Mark S.; Labrèche, France; Dumont, Martine; Winqvist, Robert; Pylkäs, Katri; Jukkola-Vuorinen, Arja; Grip, Mervi; Brauch, Hiltrud; Hamann, Ute; Brüning, Thomas; Radice, Paolo; Peterlongo, Paolo; Manoukian, Siranoush; Bonanni, Bernardo; Devilee, Peter; Tollenaar, Rob A. E. M.; Seynaeve, Caroline; van Asperen, Christi J.; Jakubowska, Anna; Lubinski, Jan; Jaworska, Katarzyna; Durda, Katarzyna; Mannermaa, Arto; Kataja, Vesa; Kosma, Veli-Matti; Hartikainen, Jaana M.; Bogdanova, Natalia V.; Antonenkova, Natalia N.; Dörk, Thilo; Kristensen, Vessela N.; Anton-Culver, Hoda; Slager, Susan; Toland, Amanda E.; Edge, Stephen; Fostira, Florentia; Kang, Daehee; Yoo, Keun-Young; Noh, Dong-Young; Matsuo, Keitaro; Ito, Hidemi; Iwata, Hiroji; Sueta, Aiko; Wu, Anna H.; Tseng, Chiu-Chen; van den Berg, David; Stram, Daniel O.; Shu, Xiao-Ou; Lu, Wei; Gao, Yu-Tang; Cai, Hui; teo, Soo Hwang; Yip, Cheng Har; Phuah, Sze Yee; Cornes, Belinda K.; Hartman, Mikael; Miao, Hui; Lim, Wei Yen; Sng, Jen-Hwei; Muir, Kenneth; Lophatananon, Artitaya; Stewart-Brown, Sarah; Siriwanarangsan, Pornthep; Shen, Chen-Yang; Hsiung, Chia-Ni; Wu, Pei-Ei; Ding, Shian-Ling; Sangrajrang, Suleeporn; Gaborieau, Valerie; Brennan, Paul; McKay, James; Blot, William J.; Signorello, Lisa B.; Cai, Qiuyin; Zheng, Wei; Deming-Halverson, Sandra; Shrubsole, Martha; Long, Jirong; Simard, Jacques; Garcia-Closas, Montse; Pharoah, Paul D. P.; Chenevix-Trench, Georgia; Dunning, Alison M.; Benitez, Javier; Easton, Douglas F.

    2013-01-01

    Breast cancer is the most common cancer among women. Common variants at 27 loci have been identified as associated with susceptibility to breast cancer, and these account for ∼9% of the familial risk of the disease. We report here a meta-analysis of 9 genome-wide association studies, including

  3. [Primary pigmented breast adenocarcinoma in a male patient].

    Science.gov (United States)

    Dauendorffer, J-N; Pages, C; Abd Alsamad, I; Bagot, M; Fraitag, S

    2013-01-01

    Pigmented mammary tumours are rare. Herein, we report the third case of primary pigmented breast adenocarcinoma in a male patient with clinical mimicking of nodular melanoma of the nipple. A male patient presented with a pigmented nodule of the right nipple. Histological examination of the lesion showed dermal and subcutaneous adenocarcinomatous proliferation. The perilesional stroma contained melanin both inside and outside macrophages, leading us to conclude on primary pigmented breast adenocarcinoma clinically mimicking nodular melanoma of the nipple. Local production of melanin by neoplastic cells in the mammary carcinoma was postulated as the cause of hyperpigmentation of the tumour. Other possible causes are transfer of melanin from overlying melanocytes of the pigmented areolar epidermis to the underlying neoplastic cells, or melanin synthesis by intratumoral melanocytes migrating from the epidermis (which strikes us as the most convincing interpretation for the reported case). Breast adenocarcinoma is a rare tumour in men and may present clinically as a pigmented lesion of the nipple, resulting in the problem of differential diagnosis with primary or metastasised nodular melanoma. Copyright © 2012 Elsevier Masson SAS. All rights reserved.

  4. ADAM33 gene silencing by promoter hypermethylation as a molecular marker in breast invasive lobular carcinoma

    Directory of Open Access Journals (Sweden)

    de Souza Emanuel M

    2009-03-01

    Full Text Available Abstract Background ADAM33 protein is a member of the family of transmembrane glycoproteins composed of multidomains. ADAM family members have different activities, such as proteolysis and adhesion, making them good candidates to mediate the extracellular matrix remodelling and changes in cellular adhesion that characterise certain pathologies and cancer development. It was reported that one family member, ADAM23, is down-regulated by promoter hypermethylation. This seems to correlate with tumour progression and metastasis in breast cancer. In this study, we explored the involvement of ADAM33, another ADAM family member, in breast cancer. Methods First, we analysed ADAM33 expression in breast tumour cell lines by RT-PCR and western blotting. We also used 5-aza-2'-deoxycytidine (5azadCR treatment and DNA bisulphite sequencing to study the promoter methylation of ADAM33 in breast tumour cell lines. We evaluated ADAM33 methylation in primary tumour samples by methylation specific PCR (MSP. Finally, ADAM33 promoter hypermethylation was correlated with clinicopathological data using the chi-square test and Fisher's exact test. Results The expression analysis of ADAM33 in breast tumour cell lines by RT-PCR revealed gene silencing in 65% of tumour cell lines. The corresponding lack of ADAM33 protein was confirmed by western blotting. We also used 5-aza-2'-deoxycytidine (5-aza-dCR demethylation and bisulphite sequencing methodologies to confirm that gene silencing is due to ADAM33 promoter hypermethylation. Using MSP, we detected ADAM33 promoter hypermethylation in 40% of primary breast tumour samples. The correlation between methylation pattern and patient's clinicopathological data was not significantly associated with histological grade; tumour stage (TNM; tumour size; ER, PR or ERBB2 status; lymph node status; metastasis or recurrence. Methylation frequency in invasive lobular carcinoma (ILC was 76.2% compared with 25.5% in invasive ductal carcinoma

  5. ADAM33 gene silencing by promoter hypermethylation as a molecular marker in breast invasive lobular carcinoma

    International Nuclear Information System (INIS)

    Seniski, Gerusa G; Zanata, Silvio M; Costa, Fabrício F; Klassen, Giseli; Camargo, Anamaria A; Ierardi, Daniela F; Ramos, Edneia AS; Grochoski, Mariana; Ribeiro, Enilze SF; Cavalli, Iglenir J; Pedrosa, Fabio O; Souza, Emanuel M de

    2009-01-01

    ADAM33 protein is a member of the family of transmembrane glycoproteins composed of multidomains. ADAM family members have different activities, such as proteolysis and adhesion, making them good candidates to mediate the extracellular matrix remodelling and changes in cellular adhesion that characterise certain pathologies and cancer development. It was reported that one family member, ADAM23, is down-regulated by promoter hypermethylation. This seems to correlate with tumour progression and metastasis in breast cancer. In this study, we explored the involvement of ADAM33, another ADAM family member, in breast cancer. First, we analysed ADAM33 expression in breast tumour cell lines by RT-PCR and western blotting. We also used 5-aza-2'-deoxycytidine (5azadCR) treatment and DNA bisulphite sequencing to study the promoter methylation of ADAM33 in breast tumour cell lines. We evaluated ADAM33 methylation in primary tumour samples by methylation specific PCR (MSP). Finally, ADAM33 promoter hypermethylation was correlated with clinicopathological data using the chi-square test and Fisher's exact test. The expression analysis of ADAM33 in breast tumour cell lines by RT-PCR revealed gene silencing in 65% of tumour cell lines. The corresponding lack of ADAM33 protein was confirmed by western blotting. We also used 5-aza-2'-deoxycytidine (5-aza-dCR) demethylation and bisulphite sequencing methodologies to confirm that gene silencing is due to ADAM33 promoter hypermethylation. Using MSP, we detected ADAM33 promoter hypermethylation in 40% of primary breast tumour samples. The correlation between methylation pattern and patient's clinicopathological data was not significantly associated with histological grade; tumour stage (TNM); tumour size; ER, PR or ERBB2 status; lymph node status; metastasis or recurrence. Methylation frequency in invasive lobular carcinoma (ILC) was 76.2% compared with 25.5% in invasive ductal carcinoma (IDC), and this difference was

  6. Phyto-oestrogens and breast cancer chemoprevention

    International Nuclear Information System (INIS)

    Limer, Jane L; Speirs, Valerie

    2004-01-01

    Phytoestrogens are polyphenol compounds of plant origin that exhibit a structural similarity to the mammalian steroid hormone 17β-oestradiol. In Asian nations the staple consumption of phyto-oestrogen-rich foodstuffs correlates with a reduced incidence of breast cancer. Human dietary intervention trials have noted a direct relationship between phyto-oestrogen ingestion and a favourable hormonal profile associated with decreased breast cancer risk. However, these studies failed to ascertain the precise effect of dietary phyto-oestrogens on the proliferation of mammary tissue. Epidemiological and rodent studies crucially suggest that breast cancer chemoprevention by dietary phyto-oestrogen compounds is dependent on ingestion before puberty, when the mammary gland is relatively immature. Phyto-oestrogen supplements are commercially marketed for use by postmenopausal women as natural and safe alternatives to hormone replacement therapy. Of current concern is the effect of phyto-oestrogen compounds on the growth of pre-existing breast tumours. Data are contradictory, with cell culture studies reporting both the oestrogenic stimulation of oestrogen receptor-positive breast cancer cell lines and the antagonism of tamoxifen activity at physiological phyto-oestrogen concentrations. Conversely, phyto-oestrogen ingestion by rodents is associated with the development of less aggressive breast tumours with reduced metastatic potential. Despite the present ambiguity, current data do suggest a potential benefit from use of phyto-oestrogens in breast cancer chemoprevention and therapy. These aspects are discussed

  7. Tumour nuclear oestrogen receptor beta 1 correlates inversely with parathyroid tumour weight.

    Science.gov (United States)

    Haglund, Felix; Rosin, Gustaf; Nilsson, Inga-Lena; Juhlin, C Christofer; Pernow, Ylva; Norenstedt, Sophie; Dinets, Andrii; Larsson, Catharina; Hartman, Johan; Höög, Anders

    2015-03-01

    Primary hyperparathyroidism (PHPT) is a common endocrinopathy, frequently caused by a parathyroid adenoma, rarely by a parathyroid carcinoma that lacks effective oncological treatment. As the majority of cases are present in postmenopausal women, oestrogen signalling has been implicated in the tumourigenesis. Oestrogen receptor beta 1 (ERB1) and ERB2 have been recently identified in parathyroid adenomas, the former inducing genes coupled to tumour apoptosis. We applied immunohistochemistry and slide digitalisation to quantify nuclear ERB1 and ERB2 in 172 parathyroid adenomas, atypical adenomas and carcinomas, and ten normal parathyroid glands. All the normal parathyroid glands expressed ERB1 and ERB2. The majority of tumours expressed ERB1 (70.6%) at varying intensities, and ERB2 (96.5%) at strong intensities. Parathyroid carcinomas expressed ERB1 in three out of six cases and ERB2 in five out of six cases. The intensity of tumour nuclear ERB1 staining significantly correlated inversely with tumour weight (P=0.011), and patients whose tumours were classified as ERB1-negative had significantly greater tumour weight as well as higher serum calcium (P=0.002) and parathyroid hormone levels (P=0.003). Additionally, tumour nuclear ERB1 was not expressed differentially with respect to sex or age of the patient. Levels of tumour nuclear ERB2 did not correlate with clinical characteristics. In conclusion, decreased ERB1 immunoreactivity is associated with increased tumour weight in parathyroid adenomas. Given the previously reported correlation with tumour-suppressive signalling, selective oestrogen receptor modulation (SERMs) may play a role in the treatment of parathyroid carcinomas. Future studies of SERMs and oestrogen treatment in PHPT should consider tumour weight as a potential factor in pharmacological responsiveness. © 2015 The authors.

  8. Biomarker assessment and molecular testing for prognostication in breast cancer.

    Science.gov (United States)

    Kos, Zuzana; Dabbs, David J

    2016-01-01

    Current treatment of breast cancer incorporates clinical, pathological and molecular data. Oestrogen receptor (ER), progesterone receptor (PR) and human epidermal growth factor receptor 2 (HER2) define prognosis and identify tumours for targeted therapy, and remain the sole established single-molecule biomarkers defining the minimum breast cancer pathology data set. Ki67 remains one of the most promising yet controversial biomarkers in breast cancer, implemented routinely in some, but not all, pathology departments. Beyond the single-molecule biomarkers, a host of multigene expression tests have been developed to interrogate the driver pathways and biology of individual breast cancers to predict clinical outcome more accurately. A minority of these assays have entered into clinical practice. This review focuses on the established biomarkers of ER, PR and HER2, the controversial but clinically implemented biomarker Ki67 and the currently marketed gene expression signatures. © 2015 John Wiley & Sons Ltd.

  9. A volume indicator for breast tumors

    International Nuclear Information System (INIS)

    Cardno, P.A.; Nicoll, J.J.

    1996-01-01

    The development of a technique that could measure quickly and accurately the change in breast cancer dimensions would be of particular benefit for elderly women where the first line of treatment in non surgical. Non surgical treatments have varying responses on the individual patient and it is important to establish as early as possible whether or not a tratment is effective. This paper looks at developing a technique that uses a series of parallel ultrasound images (1mm separation), of the breast cancer (in-vivo). These images, obtained using a 7.5 MHz linear array probe are processed to give tumour dimensions using three different methods which rely on thresholding individual images and linking the tumour peices. (author)

  10. Generation of a new bioluminescent model for visualisation of mammary tumour development in transgenic mice

    Directory of Open Access Journals (Sweden)

    Zagozdzon Agnieszka M

    2012-05-01

    Full Text Available Abstract Background Numerous transgenic models have been generated to study breast cancer. However, despite many advantages, traditional transgenic models for breast cancer are also burdened with difficulties in early detection and longitudinal observation of transgene-induced tumours, which in most cases are randomly located and occur at various time points. Methods such as palpation followed by mechanical measurement of the tumours are of limited value in transgenic models. There is a crucial need for making these previously generated models suitable for modern methods of tumour visualisation and monitoring, e.g. by bioluminescence-based techniques. This approach was successfully used in the current study. Results A new mouse strain (MMTV-Luc2 mice expressing Luc2 luciferase primarily in mammary tissue in females, with low-level background expression in internal organs, was generated and bred to homozygosity. After these mice were intercrossed with MMTV-PyVT mice, all double transgenic females developed mammary tumours by the age of 10 weeks, the localisation and progression of which could be effectively monitored using the luminescence-based in vivo imaging. Luminescence-based readout allowed for early visualisation of the locally overgrown mammary tissue and for longitudinal evaluation of local progression of the tumours. When sampled ex vivo at the age of 10 weeks, all tumours derived from MMTV-Luc2PyVT females displayed robust bioluminescent signal. Conclusions We have created a novel transgenic strain for visualisation and longitudinal monitoring of mammary tumour development in transgenic mice as an addition and/or a new and more advanced alternative to manual methods. Generation of this mouse strain is vital for making many of the existing mammary tumour transgenic models applicable for in vivo imaging techniques.

  11. Generation of a new bioluminescent model for visualisation of mammary tumour development in transgenic mice

    LENUS (Irish Health Repository)

    Zagozdzon, Agnieszka M

    2012-05-30

    AbstractBackgroundNumerous transgenic models have been generated to study breast cancer. However, despite many advantages, traditional transgenic models for breast cancer are also burdened with difficulties in early detection and longitudinal observation of transgene-induced tumours, which in most cases are randomly located and occur at various time points. Methods such as palpation followed by mechanical measurement of the tumours are of limited value in transgenic models. There is a crucial need for making these previously generated models suitable for modern methods of tumour visualisation and monitoring, e.g. by bioluminescence-based techniques. This approach was successfully used in the current study.ResultsA new mouse strain (MMTV-Luc2 mice) expressing Luc2 luciferase primarily in mammary tissue in females, with low-level background expression in internal organs, was generated and bred to homozygosity. After these mice were intercrossed with MMTV-PyVT mice, all double transgenic females developed mammary tumours by the age of 10 weeks, the localisation and progression of which could be effectively monitored using the luminescence-based in vivo imaging. Luminescence-based readout allowed for early visualisation of the locally overgrown mammary tissue and for longitudinal evaluation of local progression of the tumours. When sampled ex vivo at the age of 10 weeks, all tumours derived from MMTV-Luc2PyVT females displayed robust bioluminescent signal.ConclusionsWe have created a novel transgenic strain for visualisation and longitudinal monitoring of mammary tumour development in transgenic mice as an addition and\\/or a new and more advanced alternative to manual methods. Generation of this mouse strain is vital for making many of the existing mammary tumour transgenic models applicable for in vivo imaging techniques.

  12. Experience with ultrasonographically guided vacuum-assisted resection of benign breast tumors

    Energy Technology Data Exchange (ETDEWEB)

    Tagaya, N. [Second Department of Surgery, Dokkyo Medical University Mibu, Tochigi (Japan)], E-mail: tagaya@dokkyomed.ac.jp; Nakagawa, A. [Second Department of Surgery, Dokkyo Medical University Mibu, Tochigi (Japan); Ishikawa, Y. [Department of Breast and Endocrinological Surgery, Gunma University School of Medicine, Maebashi-shi, Gunma (Japan); Department of Pathology, Dokkyo Medical University Mibu, Tochigi (Japan); Oyama, T. [Department of Pathology, Dokkyo Medical University Mibu, Tochigi (Japan); Kubota, K. [Second Department of Surgery, Dokkyo Medical University Mibu, Tochigi (Japan)

    2008-04-15

    Aim: To evaluate the feasibility and safety of vacuum-assisted resection of benign breast tumours using an 8 G handheld device. Materials and Methods: Over a 2-year period, 22 patients with 26 breast tumours diagnosed as benign using aspiration biopsy cytology were enrolled. The mean patient age was 38 years, and the mean maximal diameter of the tumour was 13 mm. A handheld Aloka SSD 6500 ultrasonography device with a linear-type 7.5 MHz transducer was inserted into the posterior aspect of the tumour with the patient under local anaesthesia, and the tumour was resected under ultrasonographic guidance. Results: This method was employed successfully in all patients, and the mean operation time was 33 min. Post-procedure complications included subcutaneous bleeding in 12 cases and haematoma in one. The pathological diagnoses were fibroadenoma in 16 cases, mastopathy in six, and tubular adenoma and pseudoangiomatous stromal hyperplasia in two cases each, respectively. Follow-up ultrasonography revealed residual tumours in four cases (15.4%). Conclusions: Although this method is feasible and safe without severe complications, it is necessary to select appropriate patients, and to obtain informed consent regarding the possibility of recurrence or residual tumour.

  13. Correlation between conductivity and prognostic factors in invasive breast cancer using magnetic resonance electric properties tomography (MREPT)

    International Nuclear Information System (INIS)

    Kim, Soo-Yeon; Kim, Min Jung; Kim, Eun-Kyung; Moon, Hee Jung; Yoon, Jung Hyun; Shin, Jaewook; Kim, Dong-Hyun

    2016-01-01

    To investigate the correlation between conductivity and prognostic factors of invasive breast cancer using magnetic resonance electric properties tomography (MREPT). This retrospective study was approved by the Institutional Review Board, and verbal informed consent was obtained prior to breast MRI. This study included 65 women with surgically confirmed invasive breast cancers measuring 1 cm or larger on T2-weighted fast spin echo (FSE). Phase-based MREPT and the coil combination technique were used to reconstruct conductivity. Simple and multiple linear regression analysis were used to find an independent factor associated with conductivity. In total tumours, tumours with HER-2 overexpression showed lower conductivity than those without, and HER-2 overexpression was independently associated with conductivity. In 37 tumours 2 cm or larger, tumours with high mitosis or PR positivity showed higher conductivity than those without, and high mitosis and PR positivity were independently associated with conductivity. In 28 tumours 1-2 cm in size, there were no differences in conductivity according to the prognostic factors. Conductivity values measured using MREPT are associated with the HER-2 overexpression status, and may provide information about mitosis and the PR status of invasive breast cancers 2 cm or larger. (orig.)

  14. Human murine mammary tumour virus-like agents are genetically distinct from endogenous retroviruses and are not detectable in breast cancer cell lines or biopsies

    International Nuclear Information System (INIS)

    Mant, Christine; Gillett, Cheryl; D'Arrigo, Corrado; Cason, John

    2004-01-01

    It has been reported that a human murine mammary tumour virus (MMTV)-like virus (HMLV), which may be an endogenous human retrovirus (HERV), occurs in the human breast cancer cell lines T47D and MCF-7 and, in 38% of human breast cancer biopsies. As the aetiology of most breast cancers remains unknown, it is important to verify these observations in differing breast cancer populations worldwide. Thus, we sought to determine the genetic relationships between HMLVs, MMTVs, and HERVs, and to investigate the association between HMLVs and breast cancer biopsies from South London, UK. Phylogenetic analyses of the env/pol region indicated that HMLVs are indistinct from MMTVs, and that MMTVS/HMLVs exhibit only low sequence homologies with HERVs. A search of the human genome confirmed that HMLVs are not endogenous. Using MMTV polymerase chain reaction (PCR) primers described previously, we amplified DNA from all cell lines except MCF-7 and from 7 of 44 (16%) breast cancer biopsies. A restriction fragment length polymorphism assay was designed to distinguish between HMLVs and MMTVs, and upon analyses, PCR amplicons appeared to be HMLVs. To confirm these findings, amplicons from the T47D cell line and from four randomly selected breast cancer patients were sequenced. Of 106 DNA sequences obtained, 103 were homologous with a short arm of human chromosome (Chr) 3 (3p13), two with Chr 4, and one with Chr 8. None of the sequences exhibited significant nucleotide homology with MMTVs, HMLVs, or with HERVs (all <50%). Thus, we conclude that (i) HMLVs are integral members of the MMTV family; (ii) MMTVs/HMLVs are genetically distinct from HERVs; (iii) MMTV/HMLV DNA is not present in human breast cancer cell lines or clinical biopsies in our locality

  15. Cytosolic phospholipase A2-alpha expression in breast cancer is associated with EGFR expression and correlates with an adverse prognosis in luminal tumours.

    LENUS (Irish Health Repository)

    Caiazza, F

    2012-02-01

    BACKGROUND: The eicosanoid signalling pathway promotes the progression of malignancies through the production of proliferative prostaglandins (PGs). Cytosolic phospholipase A(2)alpha (cPLA(2)alpha) activity provides the substrate for cyclooxygenase-dependent PG release, and we have previously found that cPLA(2)alpha expression correlated with EGFR\\/HER2 over-expression in a small number of breast cancer cell lines. METHODS: The importance of differential cPLA(2)alpha activity in clinical breast cancer was established by relating the expression of cPLA(2)alpha in tissue samples from breast cancer patients, and two microarray-based gene expression datasets to different clinicopathological and therapeutic parameters. RESULTS: High cPLA(2)alpha mRNA expression correlated with clinical parameters of poor prognosis, which are characteristic of highly invasive tumours of the HER2-positive and basal-like subtype, including low oestrogen receptor expression and high EGFR expression. High cPLA(2)alpha expression decreased overall survival in patients with luminal cancers, and correlated with a reduced effect of tamoxifen treatment. The cPLA(2)alpha expression was an independent predictive parameter of poor response to endocrine therapy in the first 5 years of follow-up. CONCLUSION: This study shows a role of cPLA(2)alpha in luminal breast cancer progression, in which the enzyme could represent a novel therapeutic target and a predictive marker.

  16. Nonsteroidal anti-inflammatory drug use and breast cancer risk: a Danish cohort study

    DEFF Research Database (Denmark)

    Friis, Søren; Thomassen, Lars; Sørensen, Henrik T

    2008-01-01

    Epidemiologic studies investigating the effects of nonsteroidal anti-inflammatory drugs (NSAIDs) on breast cancer have yielded conflicting results. We examined the association between use of aspirin and nonaspirin NSAIDs and breast cancer risk among 28 695 women in the Danish Diet, Cancer...... and Health cohort. Information on NSAID and paracetamol use was obtained from a self-administered questionnaire completed at baseline (1993-1997) and updated through 2003 using a nationwide prescription database. Detailed information on breast cancer incidence and tumour characteristics was obtained from...... nationwide health registers. Cox proportional hazards regression was used to compute incidence rate ratios (RRs) and 95% confidence intervals (CIs). We identified 847 breast cancer cases over an average follow-up period of 7.5 years. Any NSAID use at baseline was associated with an increased incidence...

  17. The West Midlands breast cancer screening status algorithm - methodology and use as an audit tool.

    Science.gov (United States)

    Lawrence, Gill; Kearins, Olive; O'Sullivan, Emma; Tappenden, Nancy; Wallis, Matthew; Walton, Jackie

    2005-01-01

    To illustrate the ability of the West Midlands breast screening status algorithm to assign a screening status to women with malignant breast cancer, and its uses as a quality assurance and audit tool. Breast cancers diagnosed between the introduction of the National Health Service [NHS] Breast Screening Programme and 31 March 2001 were obtained from the West Midlands Cancer Intelligence Unit (WMCIU). Screen-detected tumours were identified via breast screening units, and the remaining cancers were assigned to one of eight screening status categories. Multiple primaries and recurrences were excluded. A screening status was assigned to 14,680 women (96% of the cohort examined), 110 cancers were not registered at the WMCIU and the cohort included 120 screen-detected recurrences. The West Midlands breast screening status algorithm is a robust simple tool which can be used to derive data to evaluate the efficacy and impact of the NHS Breast Screening Programme.

  18. Small regions of overlapping deletions on 6q26 in human astrocytic tumours identified using chromosome 6 tile path array CGH

    Science.gov (United States)

    Ichimura, Koichi; Mungall, Andrew J; Fiegler, Heike; Pearson, Danita M.; Dunham, Ian; Carter, Nigel P; Collins, V. Peter

    2009-01-01

    Deletions of chromosome 6 are a common abnormality in diverse human malignancies including astrocytic tumours, suggesting the presence of tumour suppressor genes (TSG). In order to help identify candidate TSGs, we have constructed a chromosome 6 tile path microarray. The array contains 1780 clones (778 PACs and 1002 BACs) that cover 98.3% of the published chromosome 6 sequences. A total of 104 adult astrocytic tumours (10 diffuse astrocytomas, 30 anaplastic astrocytomas (AA), 64 glioblastomas (GB)) were analysed using this array. Single copy number change was successfully detected and the result was in general concordant with a microsatellite analysis. The pattern of copy number change was complex with multiple interstitial deletions/gains. However, a predominance of telomeric 6q deletions was seen. Two small common and overlapping regions of deletion at 6q26 were identified. One was 1002 kb in size and contained PACRG and QKI, while the second was 199 kb and harbours a single gene, ARID1B. The data show that the chromosome 6 tile path array is useful in mapping copy number changes with high resolution and accuracy. We confirmed the high frequency of chromosome 6 deletions in AA and GB, and identified two novel commonly deleted regions that may harbour TSGs. PMID:16205629

  19. Common alleles at 6q25.1 and 1p11.2 are associated with breast cancer risk for BRCA1 and BRCA2 mutation carriers

    DEFF Research Database (Denmark)

    Antoniou, Antonis C; Kartsonaki, Christiana; Sinilnikova, Olga M

    2011-01-01

    Two single nucleotide polymorphisms (SNPs) at 6q25.1, near the ESR1 gene, have been implicated in the susceptibility to breast cancer for Asian (rs2046210) and European women (rs9397435). A genome-wide association study in Europeans identified two further breast cancer susceptibility variants: rs...... to a better understanding of the biology of tumour development in these women....

  20. Radiolabelled peptides for tumour therapy: current status and future directions. Plenary lecture at the EANM 2002

    International Nuclear Information System (INIS)

    Jong, Marion de; Kwekkeboom, Dik; Valkema, Roelf; Krenning, Eric P.

    2003-01-01

    On their plasma membranes, cells express receptor proteins with high affinity for regulatory peptides, such as somatostatin. Changes in the density of these receptors during disease, e.g. overexpression in many tumours, provide the basis for new imaging methods. The first peptide analogues successfully applied for visualisation of receptor-positive tumours were radiolabelled somatostatin analogues. The next step was to label these analogues with therapeutic radionuclides for peptide receptor radionuclide therapy (PRRT). Results from preclinical and clinical multicentre studies have already shown an effective therapeutic response when using radiolabelled somatostatin analogues to treat receptor-positive tumours. Infusion of positively charged amino acids reduces kidney uptake, enlarging the therapeutic window. For PRRT of CCK-B receptor-positive tumours, such as medullary thyroid carcinoma, radiolabelled minigastrin analogues are currently being successfully applied. The combination of different therapy modalities holds interest as a means of improving the clinical therapeutic effects of radiolabelled peptides. The combination of different radionuclides, such as 177 Lu- and 90 Y-labelled somatostatin analogues, to reach a wider tumour region of high curability, has been described. A variety of other peptide-based radioligands, such as bombesin and NPY(Y 1 ) analogues, receptors for which are expressed on common cancers such as prostate and breast cancer, are currently under development and in different phases of (pre)clinical investigation. Multi-receptor tumour targeting using the combination of bombesin and NPY(Y 1 ) analogues is promising for scintigraphy and PRRT of breast carcinomas and their lymph node metastases. (orig.)

  1. Critical research gaps and translational priorities for the successful prevention and treatment of breast cancer

    Science.gov (United States)

    2013-01-01

    Introduction Breast cancer remains a significant scientific, clinical and societal challenge. This gap analysis has reviewed and critically assessed enduring issues and new challenges emerging from recent research, and proposes strategies for translating solutions into practice. Methods More than 100 internationally recognised specialist breast cancer scientists, clinicians and healthcare professionals collaborated to address nine thematic areas: genetics, epigenetics and epidemiology; molecular pathology and cell biology; hormonal influences and endocrine therapy; imaging, detection and screening; current/novel therapies and biomarkers; drug resistance; metastasis, angiogenesis, circulating tumour cells, cancer ‘stem’ cells; risk and prevention; living with and managing breast cancer and its treatment. The groups developed summary papers through an iterative process which, following further appraisal from experts and patients, were melded into this summary account. Results The 10 major gaps identified were: (1) understanding the functions and contextual interactions of genetic and epigenetic changes in normal breast development and during malignant transformation; (2) how to implement sustainable lifestyle changes (diet, exercise and weight) and chemopreventive strategies; (3) the need for tailored screening approaches including clinically actionable tests; (4) enhancing knowledge of molecular drivers behind breast cancer subtypes, progression and metastasis; (5) understanding the molecular mechanisms of tumour heterogeneity, dormancy, de novo or acquired resistance and how to target key nodes in these dynamic processes; (6) developing validated markers for chemosensitivity and radiosensitivity; (7) understanding the optimal duration, sequencing and rational combinations of treatment for improved personalised therapy; (8) validating multimodality imaging biomarkers for minimally invasive diagnosis and monitoring of responses in primary and metastatic disease

  2. The role of polyamine catabolism in anti-tumour drug response.

    Science.gov (United States)

    Casero, R A; Wang, Y; Stewart, T M; Devereux, W; Hacker, A; Wang, Y; Smith, R; Woster, P M

    2003-04-01

    Interest in polyamine catabolism has increased since it has been directly associated with the cytotoxic response of multiple tumour types to exposure to specific anti-tumour polyamine analogues. Human polyamine catabolism was considered to be a two-step pathway regulated by the rate-limiting enzyme spermidine/spermine N(1)-acetyltransferase (SSAT) that provides substrate for an acetylpolyamine oxidase (APAO). Further, the super-induction of SSAT by several anti-tumour polyamine analogues has been implicated in the cytotoxic response of specific solid-tumour phenotypes to these agents. This high induction of SSAT has been correlated with cellular response to the anti-tumour polyamine analogues in several systems and considerable progress has been made in understanding the molecular mechanisms that regulate the analogue-induced expression of SSAT. A polyamine response element has been identified and the transacting transcription factors that bind and stimulate transcription of SSAT have been cloned and characterized. The link between SSAT activity and cellular toxicity is thought to be based on the production of H(2)O(2) by the activity of the constitutive APAO that uses the SSAT-produced acetylated polyamines. The high induction of SSAT and the subsequent activity of APAO are linked to the cytotoxic response of some tumour cell types to specific polyamine analogues. However, we have recently cloned a variably spliced human polyamine oxidase (PAOh1) that is inducible by specific polyamine analogues, efficiently uses unacetylated spermine as a substrate, and also produces toxic H(2)O(2) as a product. The results of studies with PAOh1 suggest that it is an additional enzyme in polyamine catabolism that has the potential to significantly contribute to polyamine homoeostasis and drug response. Most importantly, PAOh1 is induced by specific polyamine analogues in a tumour-phenotype-specific manner in cell lines representative of the major forms of solid tumours, including

  3. Breast Cancer in Young Nigerian Women | Ohanaka | Nigerian ...

    African Journals Online (AJOL)

    6 cases involved the right breast, 4 the left and 3 were bilateral. All the patients presented with advanced breast cancer (stage 4 disease). Ten had invasive ductal Ca while one each had lobular carcinoma, lymphoma and malignant phyllodes tumour respectively. Management was multimodal: neovadjuvant chemotherapy, ...

  4. Viscum album L. extracts in breast and gynaecological cancers: a systematic review of clinical and preclinical research

    Directory of Open Access Journals (Sweden)

    Kienle Gunver S

    2009-06-01

    Full Text Available Abstract Background Viscum album L. extracts (VAE, European mistletoe are a widely used medicinal plant extract in gynaecological and breast-cancer treatment. Methods Systematic review to evaluate clinical studies and preclinical research on the therapeutic effectiveness and biological effects of VAE on gynaecological and breast cancer. Search of databases, reference lists and expert consultations. Criteria-based assessment of methodological study quality. Results 19 randomized (RCT, 16 non-randomized (non-RCT controlled studies, and 11 single-arm cohort studies were identified that investigated VAE treatment of breast or gynaecological cancer. They included 2420, 6399 and 1130 patients respectively. 8 RCTs and 8 non-RCTs were embedded in the same large epidemiological cohort study. 9 RCTs and 13 non-RCTs assessed survival; 12 reported a statistically significant benefit, the others either a trend or no difference. 3 RCTs and 6 non-RCTs assessed tumour behaviour (remission or time to relapse; 3 reported statistically significant benefit, the others either a trend, no difference or mixed results. Quality of life (QoL and tolerability of chemotherapy, radiotherapy or surgery was assessed in 15 RCTs and 9 non-RCTs. 21 reported a statistically significant positive result, the others either a trend, no difference, or mixed results. Methodological quality of the studies differed substantially; some had major limitations, especially RCTs on survival and tumour behaviour had very small sample sizes. Some recent studies, however, especially on QoL were reasonably well conducted. Single-arm cohort studies investigated tumour behaviour, QoL, pharmacokinetics and safety of VAE. Tumour remission was observed after high dosage and local application. VAE application was well tolerated. 34 animal experiments investigated VAE and isolated or recombinant compounds in various breast and gynaecological cancer models in mice and rats. VAE showed increase of survival

  5. Elevated mammaglobin (h-MAM) expression in breast cancer is associated with clinical and biological features defining a less aggressive tumour phenotype

    International Nuclear Information System (INIS)

    Núñez-Villar, MJ; Martínez-Arribas, F; Pollán, M; Lucas, AR; Sánchez, J; Tejerina, A; Schneider, J

    2003-01-01

    Mammaglobin (h-MAM) is expressed mainly by breast epithelial cells, and this feature has been used to detect circulating breast cancer cells and occult metastases in sentinel axillary lymph nodes of breast cancer patients. However, the biological role of mammaglobin is completely unknown. We studied 128 fresh-frozen breast cancer specimens by means of reverse transcriptase–polymerase chain reaction and quantified their h-MAM mRNA expression. This was then correlated with histological and nuclear grade, oestrogen and progesterone receptor expression, c-erb-B2 and mutant p53 expression, as well as with cellular proliferation measured by means of the Ki67 labelling index, DNA ploidy and S-phase, and finally with the presence or not of invaded axillary nodes in the mastectomy specimen. In the univariate analysis, high h-MAM expression (above the median for the whole group) correlated significantly (P < 0.05) with oestrogen and progesterone receptor expression, diploid DNA content, low Ki67 labelling index, low nuclear grade and almost significantly (P = 0.058) with the absence of axillary nodal invasion in the mastectomy specimen. In a final, multivariate model, only progesterone receptor expression, diploid DNA content and absence of nodal invasion were found to be independently associated with high h-MAM expression. All of the features associated with mammaglobin expression reflect, without exception, a less aggressive tumour phenotype. Further studies are needed to clarify whether this is attributable to h-MAM expression itself, or to another mechanism of which mammaglobin expression forms part

  6. Malignant melanoma and breast carcinoma: a bidirectional correlation.

    LENUS (Irish Health Repository)

    Ho, W L

    2012-02-01

    BACKGROUND: Epidemiologic and genetic studies have suggested a bidirectional association between breast carcinoma (BC) and malignant melanoma (MM). OBSERVATION: We present a series of patients with MM and BC detected in our department within a span of 6 months, raising concerns for the high associations between the two malignancies. This led us to match the concordance of the two tumours in the National Irish Cancer Registry. CONCLUSION: The national figures provide evidence of a link between BC and MM. We recommend increased awareness among clinicians leading to more detailed surveillance of both second primary tumours. All MM patients with a family history of BC should be referred to a breast clinic. Women above the age of 40 with MM should undergo annual mammography and those less than 40 may be better evaluated with a breast MRI. All breast cancer patients should be made aware of the significance of changing moles and those with suspicious lesions referred to a dermatologist for evaluation.

  7. Malignant melanoma and breast carcinoma: a bidirectional correlation.

    LENUS (Irish Health Repository)

    Ho, W L

    2009-03-05

    BACKGROUND: Epidemiologic and genetic studies have suggested a bidirectional association between breast carcinoma (BC) and malignant melanoma (MM). OBSERVATION: We present a series of patients with MM and BC detected in our department within a span of 6 months, raising concerns for the high associations between the two malignancies. This led us to match the concordance of the two tumours in the National Irish Cancer Registry. CONCLUSION: The national figures provide evidence of a link between BC and MM. We recommend increased awareness among clinicians leading to more detailed surveillance of both second primary tumours. All MM patients with a family history of BC should be referred to a breast clinic. Women above the age of 40 with MM should undergo annual mammography and those less than 40 may be better evaluated with a breast MRI. All breast cancer patients should be made aware of the significance of changing moles and those with suspicious lesions referred to a dermatologist for evaluation.

  8. From Halsted to prevention and beyond: advances in the management of breast cancer during the twentieth century.

    Science.gov (United States)

    Fisher, B

    1999-12-01

    This commentary evaluates progress made in the treatment of breast cancer during the twentieth century. Most of the period from 1900 to 1970 was governed by the 'non-science' of anecdotalism and classical inductivism and was marked by the absence of a scientific gestalt. In keeping with the Halstedian concept that breast cancer was a local disease that spread throughout the body by contiguous extension and could be cured by more expansive surgery, the disease was treated with radical surgery. In 1950, however, a new era of enlightenment began to emerge. The awareness that there was a scientific process in which hypotheses generated from laboratory and clinical investigation could be tested by means of randomised clinical trials was a seminal advance, as were findings from studies that laid the groundwork for the modern era of steroid hormone action, including identification of oestrogen receptors. Expanding knowledge regarding tumour cell kinetics, tumour heterogeneity, and technological advances related to mammography and radiation therapy were also to play a role in making possible the advances in therapy that were subsequently to occur. In the past 30 years, as a result of laboratory and clinical investigation, the Halstedian thesis of cancer surgery was displaced by an alternative hypothesis that was supported by findings from subsequent clinical trials. A new paradigm governed surgery for breast cancer, and lumpectomy followed by radiation therapy became accepted practice. A second paradigm that governed the use of adjuvant systemic therapy arose as a result of laboratory and clinical investigation. Treating patients who were free of identifiable metastatic disease with systemic adjuvant therapy because some of them might develop distant disease in the future was a revolutionary departure from prior treatment strategy and became a new exemplar. Not only did the chemotherapy favourably alter the outcome of breast cancer patients, but the anti

  9. Targeted intraoperative radiotherapy versus whole breast radiotherapy for breast cancer (TARGIT-A trial): an international, prospective, randomised, non-inferiority phase 3 trial

    DEFF Research Database (Denmark)

    Vaidya, Jayant S; Joseph, David J; Tobias, Jeffrey S

    2010-01-01

    After breast-conserving surgery, 90% of local recurrences occur within the index quadrant despite the presence of multicentric cancers elsewhere in the breast. Thus, restriction of radiation therapy to the tumour bed during surgery might be adequate for selected patients. We compared targeted int...

  10. COMPLEXO: identifying the missing heritability of breast cancer via next generation collaboration.

    Science.gov (United States)

    Southey, Melissa C; Park, Daniel J; Nguyen-Dumont, Tu; Campbell, Ian; Thompson, Ella; Trainer, Alison H; Chenevix-Trench, Georgia; Simard, Jacques; Dumont, Martine; Soucy, Penny; Thomassen, Mads; Jønson, Lars; Pedersen, Inge S; Hansen, Thomas Vo; Nevanlinna, Heli; Khan, Sofia; Sinilnikova, Olga; Mazoyer, Sylvie; Lesueur, Fabienne; Damiola, Francesca; Schmutzler, Rita; Meindl, Alfons; Hahnen, Eric; Dufault, Michael R; Chris Chan, Tl; Kwong, Ava; Barkardóttir, Rosa; Radice, Paolo; Peterlongo, Paolo; Devilee, Peter; Hilbers, Florentine; Benitez, Javier; Kvist, Anders; Törngren, Therese; Easton, Douglas; Hunter, David; Lindstrom, Sara; Kraft, Peter; Zheng, Wei; Gao, Yu-Tang; Long, Jirong; Ramus, Susan; Feng, Bing-Jian; Weitzel, Jeffrey N; Nathanson, Katherine; Offit, Kenneth; Joseph, Vijai; Robson, Mark; Schrader, Kasmintan; Wang, San; Kim, Yeong C; Lynch, Henry; Snyder, Carrie; Tavtigian, Sean; Neuhausen, Susan; Couch, Fergus J; Goldgar, David E

    2013-06-21

    Linkage analysis, positional cloning, candidate gene mutation scanning and genome-wide association study approaches have all contributed significantly to our understanding of the underlying genetic architecture of breast cancer. Taken together, these approaches have identified genetic variation that explains approximately 30% of the overall familial risk of breast cancer, implying that more, and likely rarer, genetic susceptibility alleles remain to be discovered.

  11. The influence of elevated levels of platelet-derived endothelial cell growth factor/thymidine phosphorylase on tumourigenicity, tumour growth, and oxygenation

    International Nuclear Information System (INIS)

    Griffiths, L.; Stratford, I.J.

    1998-01-01

    Purpose: Investigation of the effect of platelet-derived endothelial cell growth factor/thymidine phosphorylase (PD-ECGF/TP) on various aspects of tumour growth in a xenograft model, including growth rate, tumourigenicity and oxygenation levels. Methods and Materials: MDA 231 breast cancer cells overexpressing PD-ECGF/TP protein were made by retroviral transduction. These cells were grown in vitro and in vivo as xenografts. Direct measurement of tumours was used to record growth parameters, while the comet assay with the bioreductive drug RSU 1069 was used to assess tumour cell oxygenation. Results: We report that MDA 231 breast tumour cell lines expressing an increased range of levels of PD-ECGF/TP have increased tumourigenicity positively related to the level of PD-ECGF/TP when implanted in nude mice. As previously reported, tumours grown from these overexpressing cell lines grew faster than the parental line. These tumours expressed higher levels of TP activity and showed increased immunocytochemical staining for PD-ECGF. In addition, the rate of growth was found to be positively related to the level of PD-ECGF/TP expressed by the tumour cells. When the comet assay was used to compare the oxygenation status of cells between the parental and PD-ECGF/TP overexpressing tumours, the latter were found to have a larger proportion of well oxygenated cells. This is consistent with these tumours having an increased and functionally competent vascular supply in response to the expression of PD-ECGF/TP. Conclusion: PD-ECGF/TP appears to be capable of influencing tumourigenicity, angiogenesis and tumour growth in a proportional manner and can directly influence tumour oxygenation levels via its role in formation of functional vasculature

  12. Development of Human Breast Milk Microbiota-Associated Mice as a Method to Identify Breast Milk Bacteria Capable of Colonizing Gut.

    Science.gov (United States)

    Wang, Xiaoxin; Lu, Huifang; Feng, Zhou; Cao, Jie; Fang, Chao; Xu, Xianming; Zhao, Liping; Shen, Jian

    2017-01-01

    Human breast milk is recognized as one of multiple important sources of commensal bacteria for infant gut. Previous studies searched for the bacterial strains shared between breast milk and infant feces by isolating bacteria and performing strain-level bacterial genotyping, but only limited number of milk bacteria were identified to colonize infant gut, including bacteria from Bifidobacterium , Staphylococcus , Lactobacillus , and Escherichia / Shigella . Here, to identify the breast milk bacteria capable of colonizing gut without the interference of bacteria of origins other than the milk or the necessity to analyze infant feces, normal chow-fed germ-free mice were orally inoculated with the breast milk collected from a mother 2 days after vaginal delivery. According to 16S rRNA gene-based denaturant gradient gel electrophoresis and Illumina sequencing, bacteria at >1% abundance in the milk inoculum were only Streptococcus (56.0%) and Staphylococcus (37.4%), but in the feces of recipient mice were Streptococcus (80.3 ± 2.3%), Corynebacterium (10.0 ± 2.6 %), Staphylococcus (7.6 ± 1.6%), and Propionibacterium (2.1 ± 0.5%) that were previously shown as dominant bacterial genera in the meconium of C-section-delivered human babies; the abundance of anaerobic gut-associated bacteria, Faecalibacterium , Prevotella , Roseburia , Ruminococcus , and Bacteroides , was 0.01-1% in the milk inoculum and 0.003-0.01% in mouse feces; the abundance of Bifidobacterium spp. was below the detection limit of Illumina sequencing in the milk but at 0.003-0.01% in mouse feces. The human breast milk microbiota-associated mouse model may be used to identify additional breast milk bacteria that potentially colonize infant gut.

  13. Expression of the glioma-associated oncogene homolog (GLI) 1 in human breast cancer is associated with unfavourable overall survival

    International Nuclear Information System (INIS)

    Haaf, Anette ten; Bektas, Nuran; Serenyi, Sonja von; Losen, Inge; Arweiler, Elfriede Christel; Hartmann, Arndt; Knüchel, Ruth; Dahl, Edgar

    2009-01-01

    The transcription factor GLI1, a member of the GLI subfamily of Krüppel-like zinc finger proteins is involved in signal transduction within the hedgehog pathway. Aberrant hedgehog signalling has been implicated in the development of different human tumour entities such as colon and lung cancer and increased GLI1 expression has been found in these tumour entities as well. In this study we questioned whether GLI1 expression might also be important in human breast cancer development. Furthermore we correlated GLI1 expression with histopathological and clinical data to evaluate whether GLI1 could represent a new prognostic marker in breast cancer treatment. Applying semiquantitative realtime PCR analysis and immunohistochemistry (IHC) GLI1 expression was analysed in human invasive breast carcinomas (n = 229) in comparison to normal human breast tissues (n = 58). GLI1 mRNA expression was furthermore analysed in a set of normal (n = 3) and tumourous breast cell lines (n = 8). IHC data were statistically interpreted using SPSS version 14.0. Initial analysis of GLI1 mRNA expression in a small cohort of (n = 5) human matched normal and tumourous breast tissues showed first tendency towards GLI1 overexpression in human breast cancers. However only a small sample number was included into these analyses and values for GLI1 overexpression were statistically not significant (P = 0.251, two-tailed Mann-Whitney U-test). On protein level, nuclear GLI1 expression in breast cancer cells was clearly more abundant than in normal breast epithelial cells (P = 0.008, two-tailed Mann-Whitney U-test) and increased expression of GLI1 protein in breast tumours significantly correlated with unfavourable overall survival (P = 0.019), but also with higher tumour stage (P < 0.001) and an increased number of tumour-positive axillar lymph nodes (P = 0.027). Interestingly, a highly significant correlation was found between GLI1 expression and the expression of SHH, a central upstream molecule of

  14. PET imaging in breast cancer

    International Nuclear Information System (INIS)

    Bombardieri, E.; Crippa, F.

    2001-01-01

    The basis of tumour imaging with PET is a specific uptake mechanism of positron emitting radiopharmaceuticals. Among the potential tracers for breast cancer (fluorodeoxyglucose, methionine, tyrosine, fluoro-estradiol, nor-progesterone), 2-deoxy-2-fluoro-D-glucose labelled with fluorine (FDG) is the most widely used radiopharmaceutical because breast cancer is particularly avid of FDG and 18 F has the advantages of the a relatively long physical half-life. Mammography is the first choice examination in studying breast masses, due to its very good performances, an excellent compliance and the best value regarding the cost/effectiveness aspects. The FDG uptake in tissue correlates with the histological grade and potential aggressiveness of breast cancer and this may have prognostic consequences. Besides the evaluation of breast lesions, FDG-PET shows a great efficacy in staging lymph node involvement prior surgery and this could have a great value in loco-regional staging. Whole body PET provides also information with regard to metastasis localizations both in soft tissue and bone, and plays an important clinical role mainly in detecting recurrent metastatic disease. In fact for its metabolic characteristics PET visualizes regions of enhanced metabolic activity and can complete other imaging modalities based on structural anatomic changes. Even though CT and MRI show superior resolution characteristics, it has been demonstrated that PET provides more accurate information in discriminating between viable tumour, fibrotic scar or necrosis. These statements are coming from the examination of more than 2000 breast cancer detection

  15. The Genetic Landscape of Breast Carcinomas with Neuroendocrine Differentiation

    Science.gov (United States)

    Marchiò, Caterina; Geyer, Felipe C; Ng, Charlotte KY; Piscuoglio, Salvatore; De Filippo, Maria R; Cupo, Marco; Schultheis, Anne M; Lim, Raymond S; Burke, Kathleen A; Guerini-Rocco, Elena; Papotti, Mauro; Norton, Larry; Sapino, Anna; Weigelt, Britta; Reis-Filho, Jorge S

    2016-01-01

    Neuroendocrine breast carcinomas (NBCs) account for 2–5% of all invasive breast cancers and are histologically similar to neuroendocrine tumours from other sites. They typically express oestrogen receptor (ER), are HER2-negative and of luminal 'intrinsic' subtype. Here we sought to define the mutational profile of NBCs, and to investigate whether NBCs and common forms of luminal (ER+/HER2-) breast cancer display distinct repertoires of somatic mutations. Eighteen ER+/HER2- NBCs, defined as harbouring >50% of tumour cells expressing chromogranin A and/or synaptophysin, and matched normal tissue were microdissected and subjected to massively parallel sequencing targeting all exons of 254 genes most frequently mutated in breast cancer and/or related to DNA repair. Their mutational repertoire was compared to that of ER+/HER2- (n=240), PAM50-defined luminal breast cancers (n=209 luminal A; n=111 luminal B) and invasive lobular carcinomas (n=127) from The Cancer Genome Atlas. NBCs were found to harbour a median of 4.5 (range 1-11) somatic mutations, similar to that of luminal B breast cancers (median=3, range 0-17) but significantly higher than that of luminal A breast cancers (median=3, range 0-18, p=0.02). The most frequently mutated genes were GATA3, FOXA1, TBX3, ARID1A (3/18, 17%), and PIK3CA, AKT1, CDH1 (2/18, 11%). NBCs less frequently harboured PIK3CA mutations than common forms of ER+/HER2, luminal A and invasive lobular carcinomas (pcancers. No TP53 somatic mutations were detected in NBCs. Compared to common forms of luminal breast cancers, NBCs display a distinctive repertoire of somatic mutations featuring lower frequency of TP53 and PIK3CA mutations, and enrichment for FOXA1, TBX3 mutations, and akin to neuroendocrine tumours from other sites, ARID1A mutations. PMID:27925203

  16. Transcriptomic profiling of curcumin-treated human breast stem cells identifies a role for stearoyl-coa desaturase in breast cancer prevention.

    Science.gov (United States)

    Colacino, Justin A; McDermott, Sean P; Sartor, Maureen A; Wicha, Max S; Rozek, Laura S

    2016-07-01

    Curcumin is a potential agent for both the prevention and treatment of cancers. Curcumin treatment alone, or in combination with piperine, limits breast stem cell self-renewal, while remaining non-toxic to normal differentiated cells. We paired fluorescence-activated cell sorting with RNA sequencing to characterize the genome-wide changes induced specifically in normal breast stem cells following treatment with these compounds. We generated genome-wide maps of the transcriptional changes that occur in epithelial-like (ALDH+) and mesenchymal-like (ALDH-/CD44+/CD24-) normal breast stem/progenitor cells following treatment with curcumin and piperine. We show that curcumin targets both stem cell populations by down-regulating expression of breast stem cell genes including ALDH1A3, CD49f, PROM1, and TP63. We also identified novel genes and pathways targeted by curcumin, including downregulation of SCD. Transient siRNA knockdown of SCD in MCF10A cells significantly inhibited mammosphere formation and the mean proportion of CD44+/CD24- cells, suggesting that SCD is a regulator of breast stemness and a target of curcumin in breast stem cells. These findings extend previous reports of curcumin targeting stem cells, here in two phenotypically distinct stem/progenitor populations isolated from normal human breast tissue. We identified novel mechanisms by which curcumin and piperine target breast stem cell self-renewal, such as by targeting lipid metabolism, providing a mechanistic link between curcumin treatment and stem cell self-renewal. These results elucidate the mechanisms by which curcumin may act as a cancer-preventive compound and provide novel targets for cancer prevention and treatment.

  17. Simultaneous CXCL12 and ESR1 CpG island hypermethylation correlates with poor prognosis in sporadic breast cancer

    International Nuclear Information System (INIS)

    Ramos, Edneia AS; Klassen, Giseli; Camargo, Anamaria A; Braun, Karin; Slowik, Renata; Cavalli, Iglenir J; Ribeiro, Enilze MSF; Pedrosa, Fábio de O; Souza, Emanuel M de; Costa, Fabrício F

    2010-01-01

    CXCL12 is a chemokine that is constitutively expressed in many organs and tissues. CXCL12 promoter hypermethylation has been detected in primary breast tumours and contributes to their metastatic potential. It has been shown that the oestrogen receptor α (ESR1) gene can also be silenced by DNA methylation. In this study, we used methylation-specific PCR (MSP) to analyse the methylation status in two regions of the CXCL12 promoter and ESR1 in tumour cell lines and in primary breast tumour samples, and correlated our results with clinicopathological data. First, we analysed CXCL12 expression in breast tumour cell lines by RT-PCR. We also used 5-aza-2'-deoxycytidine (5-aza-CdR) treatment and DNA bisulphite sequencing to study the promoter methylation for a specific region of CXCL12 in breast tumour cell lines. We evaluated CXCL12 and ESR1 methylation in primary tumour samples by methylation-specific PCR (MSP). Finally, promoter hypermethylation of these genes was analysed using Fisher's exact test and correlated with clinicopathological data using the Chi square test, Kaplan-Meier survival analysis and Cox regression analysis. CXCL12 promoter hypermethylation in the first region (island 2) and second region (island 4) was correlated with lack of expression of the gene in tumour cell lines. In the primary tumours, island 2 was hypermethylated in 14.5% of the samples and island 4 was hypermethylated in 54% of the samples. The ESR1 promoter was hypermethylated in 41% of breast tumour samples. In addition, the levels of ERα protein expression diminished with increased frequency of ESR1 methylation (p < 0.0001). This study also demonstrated that CXCL12 island 4 and ESR1 methylation occur simultaneously at a high frequency (p = 0.0220). This is the first study showing a simultaneous involvement of epigenetic regulation for both CXCL12 and ESR1 genes in Brazilian women. The methylation status of both genes was significantly correlated with histologically advanced

  18. Advancement of mass spectrometry-based proteomics technologies to explore triple negative breast cancer.

    Science.gov (United States)

    Miah, Sayem; Banks, Charles A S; Adams, Mark K; Florens, Laurence; Lukong, Kiven E; Washburn, Michael P

    2016-12-20

    Understanding the complexity of cancer biology requires extensive information about the cancer proteome over the course of the disease. The recent advances in mass spectrometry-based proteomics technologies have led to the accumulation of an incredible amount of such proteomic information. This information allows us to identify protein signatures or protein biomarkers, which can be used to improve cancer diagnosis, prognosis and treatment. For example, mass spectrometry-based proteomics has been used in breast cancer research for over two decades to elucidate protein function. Breast cancer is a heterogeneous group of diseases with distinct molecular features that are reflected in tumour characteristics and clinical outcomes. Compared with all other subtypes of breast cancer, triple-negative breast cancer is perhaps the most distinct in nature and heterogeneity. In this review, we provide an introductory overview of the application of advanced proteomic technologies to triple-negative breast cancer research.

  19. Radionuclide Tc-99m MDP Imaging for diagnosis of bone tumour at Korle-Bu Teaching Hospital (Ghana): an illustrative review

    International Nuclear Information System (INIS)

    Hasford, F.; Sosu, E.K.; Nani, K.; Sackey, T.A.; Boadu, M.; Wilson, I.K.; Addison, E.C.K.; Amuasi, J.H.

    2010-01-01

    Radioisotopes are used in diagnosing primary and metastatic bone tumours because of the high sensitivity. Diagnosing bone tumours using technetium methylene diphosphonate (Tc-99m MDP) on 9 randomly selected whole-body bone scans have been demonstrated by clinical studies of patients for illustrative review. Upon satisfactory testing of the e.cam (R) Single Photon Emission Computed Tomography at the Nuclear Medicine Department (Korle-Bu Teaching Hospital), scans of patients provided essential physiologic information about the sites of bone lesions and prognosis as shown by sequential changes in tracer uptake. The bone scintigrams were classified either as normal or pathologic. Of the 197 patients (91 males and 106 females) who underwent radioactive whole-body scans in the year 2006, the peak age at bone tumour detection was between 51 and 60 years. From qualitative analyses of the reported cases, 144 patients were diagnosed with bone tumours, but ∼ 17 % were found to be primary, while ∼ 83 % were metastatic in nature. The observation confirmed other published data that bone tumours with origin in the cells of bone are not prevalent compared to tumours that metastasize from other parts of the body, such as breast, cervix and prostate. Breast, prostate and cervical cancers contributed respectively to 34 %, 19 % and 18 % of the bone tumour cases, but only 3 % were diagnosed with osteoporosis (a relatively rare type of bone disease). (au)

  20. Primitive neuroectodermal tumour (PNET) of the kidney: a rare renal tumour in adolescents with seemingly characteristic radiological features

    International Nuclear Information System (INIS)

    Chu, Winnie C.; Reznikov, Boris; Lee, Edward Y.; Grant, Ronald M.; Cheng, Frankie W.T.; Babyn, Paul

    2008-01-01

    Primitive neuroectodermal tumours (PNETs) constitute a family of neoplasms of presumed neuroectodermal origin that predominantly present as bone or soft-tissue masses in adolescents and young adults. PNET arising in the kidney is rare. To describe the radiological features in three patients with primary renal PNET. The radiological features of primary renal PNET in three adolescent patients (age 10, 14 and 16 years) are described. Tumour thrombus extending into the renal vein and inferior vena cava was noted in all three patients. In addition, further tumour extension into the atrium was seen in two patients with extension into a pulmonary artery in one patient. Neural foraminal and intraspinal extension close to the origin of the tumour was identified in two patients. Liver, bone and lung metastases were identified. While rare, one should consider the diagnosis of PNET when encountering a renal mass with aggressive features such as inferior vena cava tumour thrombus, direct intraspinal invasion and distant metastasis. (orig.)

  1. {sup 18}F-FDG uptake in breast cancer correlates with immunohistochemically defined subtypes

    Energy Technology Data Exchange (ETDEWEB)

    Koo, Hye Ryoung [Seoul National University College of Medicine, Department of Radiology, Seoul (Korea, Republic of); Hanyang University College of Medicine, Department of Radiology, Seoul (Korea, Republic of); Park, Jeong Seon [Hanyang University College of Medicine, Department of Radiology, Seoul (Korea, Republic of); Kang, Keon Wook [Seoul National University College of Medicine, Department of Nuclear Medicine, Seoul (Korea, Republic of); Cho, Nariya; Chang, Jung Min; Bae, Min Sun; Kim, Won Hwa; Lee, Su Hyun; Seo, Mirinae; Moon, Woo Kyung [Seoul National University College of Medicine, Department of Radiology, Seoul (Korea, Republic of); Kim, Mi Young [Konkuk University Medical Center, Department of Radiology, Seoul (Korea, Republic of); Kim, Jin You [Pusan National University Hospital, Department of Radiology, Pusan (Korea, Republic of)

    2014-03-15

    To determine whether a correlation exists between maximum standardized uptake value (SUV{sub max}) on {sup 18}F-fluorodeoxyglucose positron emission tomography (FDG-PET) and the subtypes of breast cancer. This retrospective study involved 548 patients (mean age 51.6 years, range 21-81 years) with 552 index breast cancers (mean size 2.57 cm, range 1.0-14.5 cm). The correlation between {sup 18}F-FDG uptake in PET/CT, expressed as SUV{sub max}, and immunohistochemically defined subtypes (luminal A, luminal B, human epidermal growth factor receptor 2 (HER2) positive and triple negative) was analyzed. The mean SUV{sub max} value of the 552 tumours was 6.07 ± 4.63 (range 0.9-32.8). The subtypes of the 552 tumours were 334 (60 %) luminal A, 66 (12 %) luminal B, 60 (11 %) HER2 positive and 92 (17 %) triple negative, for which the mean SUV{sub max} values were 4.69 ± 3.45, 6.51 ± 4.18, 7.44 ± 4.73 and 9.83 ± 6.03, respectively. In a multivariate regression analysis, triple-negative and HER2-positive tumours had 1.67-fold (P < 0.001) and 1.27-fold (P = 0.009) higher SUV{sub max} values, respectively, than luminal A tumours after adjustment for invasive tumour size, lymph node involvement status and histologic grade. FDG uptake was independently associated with subtypes of invasive breast cancer. Triple-negative and HER2-positive breast cancers showed higher SUV{sub max} values than luminal A tumours. circle {sup 18} F-FDG PET demonstrates increased tissue glucose metabolism, a hallmark of cancers. (orig.)

  2. Musculoskeletal desmoid tumours: Diagnostic imaging appearances

    International Nuclear Information System (INIS)

    Liu, Daniel; Perera, Warren; Schlicht, Stephen; Choong, Peter; Slavin, John; Pianta, Marcus

    2015-01-01

    This study aimed to discuss the role medical imaging has on diagnosis of musculoskeletal desmoid tumours and to describe their radiological appearances on various imaging modalities. Imaging of histologically proven cases of desmoid tumours at St. Vincent's Hospital Melbourne were obtained via picture archiving communication system (PACS) and then assessed by two musculoskeletal radiologists. Suitable imagings were obtained from PACS. All imaging chosen was de-identified. Desmoid tumours can occur in many areas of the body. Imaging plays an important role in the diagnosis of these tumours and magnetic resonance imaging has been the gold standard for imaging and is the most accurate in terms of assessing tumour margins and involvement of surrounding structure.

  3. Overview of Breast Cancer in Malaysian Women: A Problem with Late Diagnosis

    Directory of Open Access Journals (Sweden)

    Abdullah N. Hisham

    2004-04-01

    Full Text Available Breast cancer is the most common cancer among Malaysian women. There is a marked geographical difference in the worldwide incidence of breast cancer, with a higher incidence in developed countries compared to developing countries. From 1998 to 2001, new cases of breast cancer presenting to the breast clinics at Hospital Kuala Lumpur and University Malaya Medical Centre, Malaysia, were reviewed; the race, age and stage at presentation were analysed. Of 774 cases seen in Hospital Kuala Lumpur, only 5.2% (40/774 were impalpable breast cancers diagnosed on mammography. The prevalent age group was 40 to 49 years, and the median age was 50 years. The average size of the tumour was 5.4 cm in diameter. Malay women appear to have larger tumours and a later stage at presentation than other ethnic groups; 50% to 60% were in late stages (Stages 3 and 4. During the same period, 752 new cases of breast cancer were seen in the University Malaya Medical Centre. The average tumour size was 4.2 cm, and 30% to 40% were in late stages. The age incidence was similar. The delay in presentation of breast cancer was attributed to a strong belief in traditional medicine, the negative perception of the disease, poverty and poor education, coupled with fear and denial. A prospective, population-based study is required to determine the demographic pattern of breast cancer and the factors delaying presentation. These findings will have important implications in future programmes to promote the early detection of breast cancer, as well as in understanding geographical as well as racial variations in the incidence of breast cancer.

  4. Age at diagnosis and breast cancer survival in iran

    NARCIS (Netherlands)

    Vostakolaei, F.A.; Broeders, M.J.M.; Rostami, N.; van Dijck, J.A.; Feuth, T.; Kiemeney, L.A.L.M.; Verbeek, A.L.M.

    2012-01-01

    Background. Tumour characteristics are the most important prognostic factors in breast cancer. Patient-related factors such as young age at diagnosis, obesity, and smoking behaviour may also modify disease outcome. Due to the absence of a unique definition for "young age breast cancer" and the

  5. Reproducibility and predictive value of scoring stromal tumour infiltrating lymphocytes in triple-negative breast cancer: a multi-institutional study.

    Science.gov (United States)

    O'Loughlin, Mark; Andreu, Xavier; Bianchi, Simonetta; Chemielik, Ewa; Cordoba, Alicia; Cserni, Gábor; Figueiredo, Paulo; Floris, Giuseppe; Foschini, Maria P; Heikkilä, Päivi; Kulka, Janina; Liepniece-Karele, Inta; Regitnig, Peter; Reiner, Angelika; Ryska, Ales; Sapino, Anna; Shalaby, Aliaa; Stovgaard, Elisabeth Specht; Quinn, Cecily; Walsh, Elaine M; Zolota, Vicky; Glynn, Sharon A; Callagy, Grace

    2018-05-17

    Several studies have demonstrated a prognostic role for stromal tumour infiltrating lymphocytes (sTILs) in triple-negative breast cancer (TNBC). The reproducibility of scoring sTILs is variable with potentially excellent concordance being achievable using a software tool. We examined agreement between breast pathologists across Europe scoring sTILs on H&E-stained sections without software, an approach that is easily applied in clinical practice. The association between sTILs and response to anthracycline-taxane NACT was also examined. Pathologists from the European Working Group for Breast Screening Pathology scored sTILs in 84 slides from 75 TNBCs using the immune-oncology biomarker working group guidance in two circulations. There were 16 participants in the first and 19 in the second circulation. Moderate agreement was achieved for absolute sTILs scores (intraclass correlation coefficient (ICC) = 0.683, 95% CI 0.601-0.767, p-value value value values (Spearman ρ = 0.727); fair for sTILs ≥ 25% (κ = 0.53) and for LPBC (κ = 0.49), but poor for sTILs as 10% increments (κ = 0.24). Increasing sTILs was significantly associated with an increased likelihood of a pathological complete response (pCR) on multivariable analysis. Increasing sTILs in TNBCs improves the likelihood of a pCR. However, inter-observer agreement is such that H&E-based assessment is not sufficiently reproducible for clinical application. Other methodologies should be explored, but may be at the cost of ease of application.

  6. Gene expression analysis in human breast cancer associated blood vessels.

    Directory of Open Access Journals (Sweden)

    Dylan T Jones

    Full Text Available Angiogenesis is essential for solid tumour growth, whilst the molecular profiles of tumour blood vessels have been reported to be different between cancer types. Although presently available anti-angiogenic strategies are providing some promise for the treatment of some cancers it is perhaps not surprisingly that, none of the anti-angiogenic agents available work on all tumours. Thus, the discovery of novel anti-angiogenic targets, relevant to individual cancer types, is required. Using Affymetrix microarray analysis of laser-captured, CD31-positive blood vessels we have identified 63 genes that are upregulated significantly (5-72 fold in angiogenic blood vessels associated with human invasive ductal carcinoma (IDC of the breast as compared with blood vessels in normal human breast. We tested the angiogenic capacity of a subset of these genes. Genes were selected based on either their known cellular functions, their enriched expression in endothelial cells and/or their sensitivity to anti-VEGF treatment; all features implicating their involvement in angiogenesis. For example, RRM2, a ribonucleotide reductase involved in DNA synthesis, was upregulated 32-fold in IDC-associated blood vessels; ATF1, a nuclear activating transcription factor involved in cellular growth and survival was upregulated 23-fold in IDC-associated blood vessels and HEX-B, a hexosaminidase involved in the breakdown of GM2 gangliosides, was upregulated 8-fold in IDC-associated blood vessels. Furthermore, in silico analysis confirmed that AFT1 and HEX-B also were enriched in endothelial cells when compared with non-endothelial cells. None of these genes have been reported previously to be involved in neovascularisation. However, our data establish that siRNA depletion of Rrm2, Atf1 or Hex-B had significant anti-angiogenic effects in VEGF-stimulated ex vivo mouse aortic ring assays. Overall, our results provide proof-of-principle that our approach can identify a cohort of

  7. Breast density and mode of detection in relation to breast cancer specific survival: a cohort study

    International Nuclear Information System (INIS)

    Olsson, Åsa; Sartor, Hanna; Borgquist, Signe; Zackrisson, Sophia; Manjer, Jonas

    2014-01-01

    The aim of this study was to examine breast density in relation to breast cancer specific survival and to assess if this potential association was modified by mode of detection. An additional aim was to study whether the established association between mode of detection and survival is modified by breast density. The study included 619 cases from a prospective cohort, The Malmö Diet and Cancer Study. Breast density estimated qualitatively, was analyzed in relation to breast cancer death, in non-symptomatic and symptomatic women, using Cox regression calculating hazard ratios (HR) with 95% confidence intervals. Adjustments were made in several steps for; diagnostic age, tumour size, axillary lymph node involvement, grade, hormone receptor status, body mass index (baseline), diagnostic period, use of hormone replacement therapy at diagnosis and mode of detection. Detection mode in relation to survival was analyzed stratified for breast density. Differences in HR following different adjustments were analyzed by Freedmans%. After adjustment for age and other prognostic factors, women with dense, as compared to fatty breasts, had an increased risk of breast cancer death, HR 2.56:1.07-6.11, with a statistically significant trend over density categories, p = 0.04. In the stratified analysis, the effect was less pronounced in non-symptomatic women, HR 2.04:0.49-8.49 as compared to symptomatic, HR 3.40:1.06-10.90. In the unadjusted model, symptomatic women had a higher risk of breast cancer death, regardless of breast density. Analyzed by Freedmans%, age, tumour size, lymph nodes, grade, diagnostic period, ER and PgR explained 55.5% of the observed differences in mortality between non-symptomatic and symptomatic cases. Additional adjustment for breast density caused only a minor change. High breast density at diagnosis may be associated with decreased breast cancer survival. This association appears to be stronger in women with symptomatic cancers but breast density could

  8. Breast carcinoma with osteoclast-like giant cells

    DEFF Research Database (Denmark)

    Gjerdrum, L M; Lauridsen, M C; Sørensen, Flemming Brandt

    2001-01-01

    Primary carcinoma with osteoclast-like giant cells is a very rare tumour of the female breast. The clinical course, histological, immunohistochemical and ultrastructural features of 61 cases of invasive duct carcinoma with osteoclast-like multinucleated giant cells (OMGCs) are reviewed and a new...... in the literature have shown that 86% of patients with these tumours are still alive after 5 years. Histologically, these tumours are invasive ductal carcinomas with OMGCs next to the neoplastic glands and within their lumen. Signs of recent and past haemorrhage are ubiquitously present in the highly vascularized...

  9. Chondrolipoma of the Breast: A Case Report | Mohammed ...

    African Journals Online (AJOL)

    Chondrolipoma of the breast is a rare mesenchymal tumour of unclear histogenesis. In this report, we present a case in an elderly female highlighting the clinical features, gross and microscopic findings and a review of the literature. (Nig J Surg Res 2001; 3: 185 – 187) KEY WORDS: Breast, Chondrolipoma ...

  10. System geometry optimization for molecular breast tomosynthesis with focusing multi-pinhole collimators

    Science.gov (United States)

    van Roosmalen, Jarno; Beekman, Freek J.; Goorden, Marlies C.

    2018-01-01

    Imaging of 99mTc-labelled tracers is gaining popularity for detecting breast tumours. Recently, we proposed a novel design for molecular breast tomosynthesis (MBT) based on two sliding focusing multi-pinhole collimators that scan a modestly compressed breast. Simulation studies indicate that MBT has the potential to improve the tumour-to-background contrast-to-noise ratio significantly over state-of-the-art planar molecular breast imaging. The aim of the present paper is to optimize the collimator-detector geometry of MBT. Using analytical models, we first optimized sensitivity at different fixed system resolutions (ranging from 5 to 12 mm) by tuning the pinhole diameters and the distance between breast and detector for a whole series of automatically generated multi-pinhole designs. We evaluated both MBT with a conventional continuous crystal detector with 3.2 mm intrinsic resolution and with a pixelated detector with 1.6 mm pixels. Subsequently, full system simulations of a breast phantom containing several lesions were performed for the optimized geometry at each system resolution for both types of detector. From these simulations, we found that tumour-to-background contrast-to-noise ratio was highest for systems in the 7 mm-10 mm system resolution range over which it hardly varied. No significant differences between the two detector types were found.

  11. Contribution of germline TP53 variants and assessment of HER-2 status among young breast cancer patients in Malaysia

    Directory of Open Access Journals (Sweden)

    Shao Yan Lau

    2017-12-01

    Full Text Available Background: Li-Fraumeni Syndrome (LFS is caused by a mutation in the TP53 tumour suppressor gene. This rare hereditary condition predisposes individuals to an increased risk of cancers including breast cancer in women at a relatively young age, which accounts for nearly 25%–30% of all LFS‑associated cancers. Studies have shown that breast tumours in women with a germline TP53 deleterious variants are associated with a human epidermal growth factor receptor 2 (HER2-positive phenotype. Taken together, this study aimed to investigate the contribution of germline TP53 variants and its association with tumour HER-2 status in a cohort of young women with breast cancer. Methods: From 2002 to 2017, 4048 women with breast cancer treated at University Malaya Medical Centre or Sime Darby Medical Centre participated in the Malaysian Breast Cancer Genetics Study. Of which, 87 patients were diagnosed before 30 years of age. All patients were analysed for germline TP53 single nucleotide variants, small insertions or deletions by amplicon‑based targeted sequencing and validated by Sanger sequencing. DNA from patients who tested negative for sequencing were subsequently evaluated for the presence of TP53 exon deletions or duplications by multiplex ligation‑dependent probe amplification. HER-2 status of breast tumours was defined by immunohistochemistry, fluorescence in situ hybridisation and/or silver in situ hybridisation. Results: 5 distinct TP53 variants were detected in 5 individuals. 3 out of 5 TP53 variants were classified as frameshift mutations, one nonsense mutation and one in-frame duplication. Variants in other genes were detected in 17 individuals. No large genomic rearrangements were detected in the remaining 65 sequencing-negative patients. The assessment of HER-2 status will be presented. Conclusions: Our results suggest that alterations in TP53 gene were identified in approximately 5.7% (5/87 of this cohort of young women with breast

  12. Differences in radiological patterns, tumour characteristics and diagnostic precision between digital mammography and screen-film mammography in four breast cancer screening programmes in Spain

    International Nuclear Information System (INIS)

    Domingo, Laia; Sala, Maria; Romero, Anabel; Belvis, Francesc; Macia, Francesc; Castells, Xavier; Sanchez, Mar; Ferrer, Joana; Salas, Dolores; Ibanez, Josefa; Vega, Alfonso; Ferrer, Francesc; Laso, M.S.

    2011-01-01

    To compare tumour characteristics between cancers detected with screen-film mammography (SFM) and digital mammography (DM) and to evaluate changes in positive predictive values (PPVs) for further assessments, for invasive procedures and for distinct radiological patterns in recalled women. 242,838 screening mammograms (171,191 SFM and 71,647 DM) from 103,613 women aged 45-69 years, performed in four population-based breast cancer screening programmes in Spain, were included. The tumour characteristics and PPVs of each group were compared. Radiological patterns (masses, calcifications, distortions and asymmetries) among recalled women were described and PPVs were evaluated. The percentages of ductal carcinoma in situ (DCIS) were higher in DM than in SFM both in the first [18.5% vs. 15.8%(p = 0.580)] and in successive screenings [23.2% vs. 15.7%(p = 0.115)]. PPVs for masses, asymmetries and calcifications were higher in DM, being statistically significant in masses (5.3% vs. 3.9%; proportion ratio: 1.37 95%CI: 1.08-1.72). Among cancers detected by calcifications, the percentage of DCIS was higher in DM (60.3% vs. 46.4%, p = 0.060). PPVs were higher when DM was used, both for further assessments and for invasive procedures, with similar cancer detection rates and no statistically significant differences in tumour characteristics. The greatest improvements in PPVs were found for masses. (orig.)

  13. Differences in radiological patterns, tumour characteristics and diagnostic precision between digital mammography and screen-film mammography in four breast cancer screening programmes in Spain

    Energy Technology Data Exchange (ETDEWEB)

    Domingo, Laia; Sala, Maria [IMIM-Hospital del Mar, Department of Epidemiology and Evaluation, Barcelona (Spain); CIBER de Epidemiologia y Salud Publica (CIBERESP), Barcelona (Spain); Universitat Autonoma de Barcelona (UAB), EHEA Doctoral Program in Public Health. Department of Pediatrics, Obstetrics and Gynecology, Preventive Medicine and Public Health, Barcelona (Spain); Romero, Anabel; Belvis, Francesc; Macia, Francesc; Castells, Xavier [IMIM-Hospital del Mar, Department of Epidemiology and Evaluation, Barcelona (Spain); CIBER de Epidemiologia y Salud Publica (CIBERESP), Barcelona (Spain); Sanchez, Mar [Government of Cantabria, General Directorate of Public Health, Department of Health, Santander (Spain); Ferrer, Joana [Radiology Unit. Hospital Santa Caterina, Girona (Spain); Salas, Dolores; Ibanez, Josefa [General Directorate Public Health and Centre for Public Health Research (CSISP), Valencia (Spain); Vega, Alfonso [Hospital Universitario Marques de Valdecilla, Radiology Unit, Santander (Spain); Ferrer, Francesc [Hospital del Mar, Radiology and Nuclear Medicine Service, Barcelona (Spain); Laso, M.S. [Breast Cancer Screening Unit Burjassot, Valencia (Spain)

    2011-09-15

    To compare tumour characteristics between cancers detected with screen-film mammography (SFM) and digital mammography (DM) and to evaluate changes in positive predictive values (PPVs) for further assessments, for invasive procedures and for distinct radiological patterns in recalled women. 242,838 screening mammograms (171,191 SFM and 71,647 DM) from 103,613 women aged 45-69 years, performed in four population-based breast cancer screening programmes in Spain, were included. The tumour characteristics and PPVs of each group were compared. Radiological patterns (masses, calcifications, distortions and asymmetries) among recalled women were described and PPVs were evaluated. The percentages of ductal carcinoma in situ (DCIS) were higher in DM than in SFM both in the first [18.5% vs. 15.8%(p = 0.580)] and in successive screenings [23.2% vs. 15.7%(p = 0.115)]. PPVs for masses, asymmetries and calcifications were higher in DM, being statistically significant in masses (5.3% vs. 3.9%; proportion ratio: 1.37 95%CI: 1.08-1.72). Among cancers detected by calcifications, the percentage of DCIS was higher in DM (60.3% vs. 46.4%, p = 0.060). PPVs were higher when DM was used, both for further assessments and for invasive procedures, with similar cancer detection rates and no statistically significant differences in tumour characteristics. The greatest improvements in PPVs were found for masses. (orig.)

  14. The utility of ultrasound superb microvascular imaging for evaluation of breast tumour vascularity: comparison with colour and power Doppler imaging regarding diagnostic performance.

    Science.gov (United States)

    Park, A Y; Seo, B K; Woo, O H; Jung, K S; Cho, K R; Park, E K; Cha, S H; Cha, J

    2018-03-01

    To investigate the utility of superb microvascular imaging (SMI) for evaluating the vascularity of breast masses in comparison with colour or power Doppler ultrasound (US) and the effect on diagnostic performance. A total of 191 biopsy-proven masses (99 benign and 92 malignant) in 166 women with greyscale, colour Doppler, power Doppler, and SMI images were enrolled in this retrospective study. Three radiologists analysed the vascular images using a three-factor scoring system to evaluate the number, morphology, and distribution of tumour vessels. They assessed the Breast Imaging-Reporting and Data System categories for greyscale US alone and combinations of greyscale US and each type of vascular US. The Kruskal-Wallis test was performed and the area under the receiver-operating characteristic curve (AUC) measured. On SMI, vascular scores were compared between benign and malignant masses and the optimal cut-off value for the overall score was determined. SMI showed higher vascular scores than colour or power Doppler US and malignant masses had higher scores than benign masses (ppower Doppler US (AUC, 0.815 versus 0.774, 0.789, 0.791; ppower Doppler US for characterising the vascularity in breast masses and improving diagnostic performance. Copyright © 2017 The Royal College of Radiologists. Published by Elsevier Ltd. All rights reserved.

  15. Hormone receptor expression in male breast cancers | Akosa ...

    African Journals Online (AJOL)

    Male breast cancers are rare but have been found in higher proportions in Black Africans. Prognostic factors for breast cancers include tumour size, grade and stage, and hormone receptor status. The hormone receptor status is an invaluable guide in the use of adjuvant endocrine therapy, but none of the reports available ...

  16. A population based study of variations in operation rates for breast cancer, of comorbidity and prognosis at diagnosis: failure to operate for early breast cancer in older women.

    Science.gov (United States)

    Bates, T; Evans, T; Lagord, C; Monypenny, I; Kearins, O; Lawrence, G

    2014-10-01

    Older women are less likely to have surgery for operable breast cancer. This population-based study examines operation rates by age and identifies groups which present with early or late disease. 37 000 cancer registrations for 2007 were combined with Hospital Episode Statistics comorbidity data for England. Operation rates were examined by age, ethnicity, deprivation, comorbidity, screen-detection, tumour size, grade and nodal status. Early and late presentation were correlated with Nottingham Prognostic Index (NPI) groups and tumour size. The proportion of women not having surgery increased from 7-10% at ages 35-69 to 82% from age 90. From age 70, the proportion not having surgery rose by an average of 3.1% per year of age. Women with a Charlson Comorbidity Index score of ≥1 (which increased with age), with tumours >50 mm or who were node positive, were less likely to have surgery. Although women aged 70-79 were more likely to have larger tumours, their tumours were also more likely to have an excellent or good NPI (p ethnic groups (p ethnic groups presented with more advanced tumours. Older women had larger tumours which were otherwise of good prognosis, and this would not account for the failure to operate which may in part be related to comorbidity in this age group. Copyright © 2014 Elsevier Ltd. All rights reserved.

  17. Pre-treatment functional MRI of breast cancer: T2* evaluation at 3 T and relationship to dynamic contrast-enhanced and diffusion-weighted imaging.

    Science.gov (United States)

    Kousi, Evanthia; O'Flynn, Elizabeth A M; Borri, Marco; Morgan, Veronica A; deSouza, Nandita M; Schmidt, Maria A

    2018-05-31

    Baseline T2* relaxation time has been proposed as an imaging biomarker in cancer, in addition to Dynamic Contrast-Enhanced (DCE) MRI and diffusion-weighted imaging (DWI) parameters. The purpose of the current work is to investigate sources of error in T2* measurements and the relationship between T2* and DCE and DWI functional parameters in breast cancer. Five female volunteers and thirty-two women with biopsy proven breast cancer were scanned at 3 T, with Research Ethics Committee approval. T2* values of the normal breast were acquired from high-resolution, low-resolution and fat-suppressed gradient-echo sequences in volunteers, and compared. In breast cancer patients, pre-treatment T2*, DCE MRI and DWI were performed at baseline. Pathologically complete responders at surgery and non-responders were identified and compared. Principal component analysis (PCA) and cluster analysis (CA) were performed. There were no significant differences between T2* values from high-resolution, low-resolution and fat-suppressed datasets (p > 0.05). There were not significant differences between baseline functional parameters in responders and non-responders (p > 0.05). However, there were differences in the relationship between T2* and contrast-agent uptake in responders and non-responders. Voxels of similar characteristics were grouped in 5 clusters, and large intra-tumoural variations of all parameters were demonstrated. Breast T2* measurements at 3 T are robust, but spatial resolution should be carefully considered. T2* of breast tumours at baseline is unrelated to DCE and DWI parameters and contribute towards describing functional heterogeneity of breast tumours. Copyright © 2018 The Authors. Published by Elsevier Inc. All rights reserved.

  18. Geographic access to radiation therapy facilities and disparities of early-stage breast cancer treatment

    Directory of Open Access Journals (Sweden)

    Yan Lin

    2018-05-01

    Full Text Available Few studies of breast cancer treatment have focused on the Northern Plains of the United States, an area with a high mastectomy rate. This study examined the association between geographic access to radiation therapy facilities and receipt of breast cancer treatments among early-stage breast cancer patients in South Dakota. Based on 4,209 early-stage breast cancer patients diagnosed between 2001 and 2012 in South Dakota, the study measured geographic proximity to radiation therapy facilities using the shortest travel time for patients to the closest radiation therapy facility. Two-level logistic regression models were used to estimate for early stage cases i the odds of mastectomy versus breast conserving surgery (BCS; ii the odds of not receiving radiation therapy after BCS versus receiving follow-up radiation therapy. Covariates included race/ethnicity, age at diagnosis, tumour grade, tumour sequence, year of diagnosis, census tract-level poverty rate and urban/rural residence. The spatial scan statistic method was used to identify geographic areas with significantly higher likelihood of experiencing mastectomy. The study found that geographic accessibility to radiation therapy facilities was negatively associated with the likelihood of receiving mastectomy after adjustment for other covariates, but not associated with radiation therapy use among patients receiving BCS. Compared with patients travelling less than 30 minutes to a radiation therapy facility, patients travelling more than 90 minutes were about 1.5 times more likely to receive mastectomy (odds ratio, 1.51; 95% confidence interval, 1.08-2.11 and patients travelling more than 120 minutes were 1.7 times more likely to receive mastectomy (odds ratio, 1.70; 95% confidence interval, 1.19-2.42. The study also identified a statistically significant cluster of patients receiving mastectomy who were located in south-eastern South Dakota, after adjustment for other factors. Because

  19. The Complex Interaction of Matrix Metalloproteinases in the Migration of Cancer Cells through Breast Tissue Stroma

    Directory of Open Access Journals (Sweden)

    Kerry J. Davies

    2014-01-01

    Full Text Available Breast cancer mortality is directly linked to metastatic spread. The metastatic cell must exhibit a complex phenotype that includes the capacity to escape from the primary tumour mass, invade the surrounding normal tissue, and penetrate into the circulation before proliferating in the parenchyma of distant organs to produce a metastasis. In the normal breast, cellular structures change cyclically in response to ovarian hormones leading to regulated cell proliferation and apoptosis. Matrix metalloproteinases (MMPs are a family of zinc dependent endopeptidases. Their primary function is degradation of proteins in the extracellular matrix to allow ductal progression through the basement membrane. A complex balance between matrix metalloproteinases and their inhibitors regulate these changes. These proteinases interact with cytokines, growth factors, and tumour necrosis factors to stimulate branching morphologies in normal breast tissues. In breast cancer this process is disrupted facilitating tumour progression and metastasis and inhibiting apoptosis increasing the life of the metastatic cells. This paper highlights the role of matrix metalloproteinases in cell progression through the breast stroma and reviews the complex relationships between the different proteinases and their inhibitors in relation to breast cancer cells as they metastasise.

  20. Influence of internal mammary node irradiation on long-term outcome and contralateral breast cancer incidence in node-negative breast cancer patients

    International Nuclear Information System (INIS)

    Courdi, Adel; Chamorey, Emmanuel; Ferrero, Jean-Marc; Hannoun-Lévi, Jean-Michel

    2013-01-01

    Background and purpose: There is no general consensus concerning irradiation (RT) of internal mammary nodes (IMN) in axillary node-negative breast cancer. Based on a large series of patients treated in a single institute and followed up for a long period of time, we looked at the influence of IMN RT on late outcome of these patients as well as the development of contralateral breast cancer (CBC). Patients and methods: The study was based on 1630 node-negative breast cancer patients treated in our institution between 1975 and 2008 with primary conservative surgery and axillary dissection or sentinel node examination. All patients received post-operative breast RT. IMN RT was more frequent in inner or central tumours. Kaplan–Meier (K–M) overall survival (OS), cancer-specific survival (CSS), and disease-free survival (DFS) according to IMN RT were calculated for all patients and for patients with inner/central tumours. The K–M rate of contralateral breast cancer (CBC) was also analysed and correlated with IMN RT. Results: Prognostic variables such as tumour size, histological grade, and hormone receptors were not significantly different in the groups having received IMN RT or not. Considering all patients, OS was strictly comparable in the 2 groups: 10-year values were 85% (IMN RT) and 86% (no IMN RT), respective values at 20 years were 66.6% and 61.0% (p = 0.95). However, in patients presenting with inner/central tumours, OS was significantly improved in the IMN RT group with respective values of 92.5% and 87.2% at 10 years, and 80.2% and 63.3% at 20 years: Hazard ratio (HR) = 0.56 (0.37–0.85); p = 0.0052. Again, CSS was improved in patients with inner/central tumours having received IMN RT, with 20-year rates of 89.5% versus 79.1% in patients not receiving IMN RT (p = 0.047). No difference in DFS was noticed. The actuarial rate of CBC development was comparable between patients having received IMN RT and other patients. However, considering only patients

  1. Plasma transforming growth factor beta levels in breast cancer patients

    NARCIS (Netherlands)

    Sminia, P; Barten, AD; Van Waarde, MAWH; Vujaskovic, Z; Van Tienhoven, G

    1998-01-01

    We investigated whether the concentration of circulating transforming growth factor beta (TGF beta) yields diagnostic value in breast cancer. Blood was collected from twenty stage I and II breast cancer patients both prior to treatment and after surgical excision of the tumour. Both latent and

  2. Plasma transforming growth factor beta levels in breast cancer patients

    NARCIS (Netherlands)

    Sminia, P.; Barten, A. D.; van Waarde, M. A.; Vujaskovic, Z.; van Tienhoven, G.

    1998-01-01

    We investigated whether the concentration of circulating transforming growth factor beta (TGFbeta) yields diagnostic value in breast cancer. Blood was collected from twenty stage I and II breast cancer patients both prior to treatment and after surgical excision of the tumour. Both latent and active

  3. Intra-tumour IgA1 is common in cancer and is correlated with poor prognosis in bladder cancer.

    Directory of Open Access Journals (Sweden)

    Charlotte Welinder

    2016-08-01

    Full Text Available A high frequency of IgA1-positive tumour cells was found in tissue micro-arrays of oesophagus, colon, testis, lung, breast, bladder and ovarian cancer. IgA1 was observed in the cytoplasm and the plasma membrane. A correlation was found between intra-tumour IgA1 and poor overall survival in a large cohort of bladder cancer patients (n = 99, p = 0.011, log-rank test. The number of IgA1-positive tumour cells was also found to be higher in female than male bladder cancer patients. The presence of IgA1 was confirmed in formalin-fixed paraffin-embedded ovarian carcinoma samples using LC-MS/MS analysis. Uptake of IgA1 was also observed in breast cancer and melanoma cell lines when cultivated in the presence of serum from healthy individuals, indicating a possible origin of the IgA1 antibodies in cancer cells.

  4. Magnetic resonance imaging appearances in primary and secondary angiosarcoma of the breast.

    LENUS (Irish Health Repository)

    O'Neill, Ailbhe C

    2014-04-01

    Angiosarcomas are malignant tumours of endovascular origin. They are rare tumours accounting for 0.04-1% of all breast malignancies. Two different forms are described: primary, occurring in young women, and secondary angiosarcoma, which occurs in older women with a history of breast-conserving surgery and radiation therapy. Imaging findings on mammography and ultrasound are non-specific, but magnetic resonance imaging with dynamic contrast enhancement is more informative. We present two cases - one of primary and one of secondary angiosarcoma - and review the imaging findings.

  5. Influence of previous breast surgery in sentinel lymph node biopsy in patients with breast cancer.

    Science.gov (United States)

    López-Prior, V; Díaz-Expósito, R; Casáns Tormo, I

    The aim of this study was to review the feasibility of selective sentinel lymph node biopsy in patients with previous surgery for breast cancer, as well as to examine the factors that may interfere with sentinel node detection. A retrospective review was performed on 91 patients with breast cancer and previous breast surgery, and who underwent sentinel lymph node biopsy. Patients were divided into two groups according to their previous treatment: aesthetic breast surgery in 30 patients (group I) and breast-conserving surgery in 61 (group II). Lymphoscintigraphy was performed after an intra-tumour injection in 21 cases and a peri-areolar injection in 70 cases. An analysis was made of lymphatic drainage patterns and overall sentinel node detection according to clinical, pathological and surgical variables. The overall detection of the sentinel lymph node in the lymphoscintigraphy was 92.3%, with 7.7% of extra-axillary drainages. The identification rate was similar after aesthetic breast surgery (93.3%) and breast-conserving surgery (91.8%). Sentinel lymph nodes were found in the contralateral axilla in two patients (2.2%), and they were included in the histopathology study. The non-identification rate in the lymphoscintigraphy was 7.7%. There was a significantly higher non-detection rate in the highest histological grade tumours (28.6% grade III, 4.5% grade I and 3.6% grade II). Sentinel lymph node biopsy in patients with previous breast surgery is feasible and deserves further studies to assess the influence of different aspects in sentinel node detection in this clinical scenario. A high histological grade was significantly associated with a lower detection. Copyright © 2017 Elsevier España, S.L.U. y SEMNIM. All rights reserved.

  6. Neurofibromatosis type 1: brain stem tumours

    International Nuclear Information System (INIS)

    Bilaniuk, L.T.; Molloy, P.T.; Zimmerman, R.A.; Phillips, P.C.; Vaughan, S.N.; Liu, G.T.; Sutton, L.N.; Needle, M.

    1997-01-01

    We describe the clinical and imaging findings of brain stem tumours in patients with neurofibromatosis type 1 (NF1). The NF1 patients imaged between January 1984 and January 1996 were reviewed and 25 patients were identified with a brain stem tumour. Clinical, radiographical and pathological results were obtained by review of records and images. Brain stem tumour identification occurred much later than the clinical diagnosis of NF1. Medullary enlargement was most frequent (68 %), followed by pontine (52 %) and midbrain enlargement (44 %). Patients were further subdivided into those with diffuse (12 patients) and those with focal (13 patients) tumours. Treatment for hydrocephalus was required in 67 % of the first group and only 15 % of the second group. Surgery was performed in four patients and revealed fibrillary astrocytomas, one of which progressed to an anaplastic astrocytoma. In 40 % of patients both brain stem and optic pathway tumours were present. The biological behaviour of brain stem tumours in NF1 is unknown. Diffuse tumours in the patients with NF1 appear to have a much more favourable prognosis than patients with similar tumours without neurofibromatosis type 1. (orig.). With 7 figs., 3 tabs

  7. Apoptotic Cell Death and the Proliferative Capacity of Human Breast Cancers

    Directory of Open Access Journals (Sweden)

    Gabriele A. Losa

    1998-01-01

    Full Text Available The proliferative capacity (%S‐phase fraction, DNA ploidy, apoptosis frequency (DNA fragmentation and steroid hormone receptor status (estrogen receptor, ER; progesterone receptor, PR of 110 samples of human breast tissues with ductal invasive carcinoma were measured using biochemical and cytofluorimetric procedures. The DNA fragmentation had a left‐skewed frequency distribution and an overall median value of 1.64%, whilst the median %S‐phase fraction was 8%. The median %DNA fragmentation and %S‐phase fraction were 1.96% and 16% in hyperdiploid tumours (n=29; DNA index >1.1 higher than in hypodiploid tumors (n=10; DNA index 0.96, 0.38% and 7.5%. DNA diploid tumours (n=71 had median %DNA fragmentation and %S‐phase values of 1.68% and 6%, consistently lower than the median values of DNA hyperdiploid tumours. The ER content of hypodiploid tumours was about one half (median: 5.9 fmol/mg the median values in hyperdiploid (10.6 fmol/mg and diploid tumours (14.6 fmol/mg. This may correlate with the lowest frequency of apoptosis in hypodiploid tumours, at least when measured by biochemical methods which only detect cells in the late phases of apoptosis. In contrast, the median PR was lowest in hyperdiploid tumours than in hypo and/or diploid tumours. The %S‐phase/%fragmented DNA ratio for the hypodiploid tumours was 19.7, significantly higher than the ratios for hyperdiploid (8.2 and diploid tumours (3.6. These findings indicated that there is an imbalance between proliferative capacity and cell death or growth arrest in human breast tumours. This imbalance may well be linked to a loss of steroid hormone control.

  8. Methylator phenotype of malignant germ cell tumours in children identifies strong candidates for chemotherapy resistance.

    Science.gov (United States)

    Jeyapalan, J N; Noor, D A Mohamed; Lee, S-H; Tan, C L; Appleby, V A; Kilday, J P; Palmer, R D; Schwalbe, E C; Clifford, S C; Walker, D A; Murray, M J; Coleman, N; Nicholson, J C; Scotting, P J

    2011-08-09

    Yolk sac tumours (YSTs) and germinomas are the two major pure histological subtypes of germ cell tumours. To date, the role of DNA methylation in the aetiology of this class of tumour has only been analysed in adult testicular forms and with respect to only a few genes. A bank of paediatric tumours was analysed for global methylation of LINE-1 repeat elements and global methylation of regulatory elements using GoldenGate methylation arrays. Both germinomas and YSTs exhibited significant global hypomethylation of LINE-1 elements. However, in germinomas, methylation of gene regulatory regions differed little from control samples, whereas YSTs exhibited increased methylation at a large proportion of the loci tested, showing a 'methylator' phenotype, including silencing of genes associated with Caspase-8-dependent apoptosis. Furthermore, we found that the methylator phenotype of YSTs was coincident with higher levels of expression of the DNA methyltransferase, DNA (cytosine-5)-methyltransferase 3B, suggesting a mechanism underlying the phenotype. Epigenetic silencing of a large number of potential tumour suppressor genes in YSTs might explain why they exhibit a more aggressive natural history than germinomas and silencing of genes associated with Caspase-8-dependent cell death might explain the relative resistance of YSTs to conventional therapy.

  9. The role of neoadjuvant chemotherapy in the surgical management of women with breast cancer in a middle-income country

    Directory of Open Access Journals (Sweden)

    Cheng-Har Yip

    2017-03-01

    Full Text Available Neoadjuvant chemotherapy (NAC in women with large breast tumours can downsize tumours to allow for breast conservation surgery (BCS. The aim of this study is to compare the BCS rate between those who had NAC versus those who underwent surgery first and to determine the factors affecting response rate. 1,183 patients, who had surgery for breast cancer in a single institution from December 2012 to December 2015, were included in this study. 80 (6.8% patients had NAC. Patient and tumours characteristics, and type of surgery were compared between those who had surgery first or surgery after NAC. Variables affecting the response rate were analyzed. The BCS rate between the surgery first and the NAC group were similar (34.2% versus 35%. The pathological complete response (PCR rate, partial response rate and stable disease rate was 22.5%, 65% and 12.5%, respectively. PCR rate was not significantly affected by subtype of breast cancer, although there was a tendency for PCR to be higher in ER-negative (32.4%, PR-negative (26.1% HER2-positive (28.6%, HER2 overexpressing (37.5% and TNBC (22.7% tumours. NAC is able to downsize tumour to achieve BCS rate that is similar to those without NAC.

  10. Results of level-ii oncoplasty in breast cancer patients: an early experience from a tertiary care hospital in pakistan

    International Nuclear Information System (INIS)

    Qureshi, S.; Ghazanfar, S.; Quraishy, S.; Iqbal, S.

    2014-01-01

    Objective: To assess the oncologic and cosmetic outcomes for breast cancer patients who underwent breast conservation therapy using Level II oncoplasty techniques. Methods: The prospective, non-randomised and descriptive study was conducted at the Department of Surgery, Unit IV of Civil Hospital, Karachi, from December 2009 to November 2011 in which 21 consecutive women with breast carcinoma who underwent wide local excision with remodeling mammoplasty were enrolled. All patients were reviewed by the surgeon and medical oncologist every 3 months for the first year. A grading system of 5-1 (excellent to poor) was employed and those with 3 or more were considered to have acceptable results. Results: The mean patient age was 45.38+-10.09 years (range: 26-70); 11 (52.3%) were premenopausal and 10 (47.7%) were postmenopausal; and 5 (27.8%) had family history of breast cancer. The mean size of the tumour determined by histology was 59.9+-3.18 mm (range: 25-150). Eight (30%) patients received preoperative chemotherapy to downsize the tumour. Three (14.2%) patients received preoperative radiotherapy. Mean operative time was 1.59+-0.52 hours (range: 1-2.5 hours). Mean volume of breast tissue excised from the breast containing the tumour was 545.27+-412.06 cm3 (range: 43.70-1456). Assessment of excision margins showed no tumour at the margins of 19 (90.4%) patients. Two (9.5%) patients had close but negative margins. The mean hospital stay was 7.10+-3.30 days (range: 4-15). There were early complications in 4 (19%) patients. One (4.76%) patient had late complications. Two (9.5%) patients developed tumour recurrence; both had an ipsilateral tumour recurrence. None of the patients developed metastases and one died of cardiac problem. Twenty (95.2%) patients had an acceptable post-surgical cosmetic result. Conclusion: Level II oncoplasty was a safe option in breast conservation allowing large sized and difficult-location tumour excision with good cosmetic outcome in the study

  11. Why did the breast cancer lymph node status distribution improve in Denmark in the pre-mammography screening period of 1978-1994?

    International Nuclear Information System (INIS)

    Rostgaard, Klaus; Lynge, Elsebeth; Vaeth, Michael; Rootzen, Helle

    2010-01-01

    Background. Danish breast cancer patients diagnosed in 1978-1994 experienced a trend over time towards a more favourable distribution of lymph node status at time of diagnosis, which was not due to mammography screening. We investigated how this trend could be explained by patient characteristics at diagnosis: age (biological processes), calendar period (e.g. environmental changes), birth cohort (living conditions over a life time), post-menopausal status (a predictor of less favourable nodal status), and tumour diameter (a marker of detection time). Material and methods. The data set consisted of 22 955 patients aged 30-69 years at time of diagnosis with known lymph node status, known tumour diameter, known menopausal status, and clinically detected tumours, available from the Danish Breast Cancer Cooperative Group (DBCG). Age, period, cohort, menopausal status, and tumour diameter were used as predictors in generalised linear models with either node-positive status (at least one of the excised lymph nodes being tumour-positive) or severely node-positive status (at least half of the excised lymph nodes being tumour-positive) as outcomes. Lymph node status was assessed both empirically and estimated using an EM algorithm in order to reduce misclassification. Results and discussion. We found that the improved lymph node status distribution was most likely a period effect due to a combination of earlier detection of clinical tumours, explaining most of the trend in node-positive breast cancer and half of the trend in severely node-positive breast cancer, and some unknown factor affecting lymph node status but not necessarily other tumour characteristics

  12. Do clinical, histological or immunohistochemical primary tumour characteristics translate into different 18F-FDG PET/CT volumetric and heterogeneity features in stage II/III breast cancer?

    International Nuclear Information System (INIS)

    Groheux, David; Martineau, Antoine; Merlet, Pascal; Majdoub, Mohamed; Hatt, Mathieu; Visvikis, Dimitris; Tixier, Florent; Le Rest, Catherine Cheze; Espie, Marc; Roquancourt, Anne de; Hindie, Elif

    2015-01-01

    The aim of this retrospective study was to determine if some features of baseline 18 F-FDG PET images, including volume and heterogeneity, reflect clinical, histological or immunohistochemical characteristics in patients with stage II or III breast cancer (BC). Included in the present retrospective analysis were 171 prospectively recruited patients with stage II/III BC treated consecutively at Saint-Louis hospital. Primary tumour volumes were semiautomatically delineated on pretreatment 18 F-FDG PET images. The parameters extracted included SUV max , SUV mean , metabolically active tumour volume (MATV), total lesion glycolysis (TLG) and heterogeneity quantified using the area under the curve of the cumulative histogram and textural features. Associations between clinical/histopathological characteristics and 18 F-FDG PET features were assessed using one-way analysis of variance. Areas under the ROC curves (AUC) were used to quantify the discriminative power of the features significantly associated with clinical/histopathological characteristics. T3 tumours (>5 cm) exhibited higher textural heterogeneity in 18 F-FDG uptake than T2 tumours (AUC <0.75), whereas there were no significant differences in SUV max and SUV mean . Invasive ductal carcinoma showed higher SUV max values than invasive lobular carcinoma (p = 0.008) but MATV, TLG and textural features were not discriminative. Grade 3 tumours had higher FDG uptake (AUC 0.779 for SUV max and 0.694 for TLG), and exhibited slightly higher regional heterogeneity (AUC 0.624). Hormone receptor-negative tumours had higher SUV values than oestrogen receptor-positive (ER-positive) and progesterone receptor-positive tumours, while heterogeneity patterns showed only low-level variation according to hormone receptor expression. HER-2 status was not associated with any of the image features. Finally, SUV max , SUV mean and TLG significantly differed among the three phenotype subgroups (HER2-positive, triple-negative and ER

  13. A target based approach identifies genomic predictors of breast cancer patient response to chemotherapy

    Directory of Open Access Journals (Sweden)

    Hallett Robin M

    2012-05-01

    Full Text Available Abstract Background The efficacy of chemotherapy regimens in breast cancer patients is variable and unpredictable. Whether individual patients either achieve long-term remission or suffer recurrence after therapy may be dictated by intrinsic properties of their breast tumors including genetic lesions and consequent aberrant transcriptional programs. Global gene expression profiling provides a powerful tool to identify such tumor-intrinsic transcriptional programs, whose analyses provide insight into the underlying biology of individual patient tumors. For example, multi-gene expression signatures have been identified that can predict the likelihood of disease reccurrence, and thus guide patient prognosis. Whereas such prognostic signatures are being introduced in the clinical setting, similar signatures that predict sensitivity or resistance to chemotherapy are not currently clinically available. Methods We used gene expression profiling to identify genes that were co-expressed with genes whose transcripts encode the protein targets of commonly used chemotherapeutic agents. Results Here, we present target based expression indices that predict breast tumor response to anthracycline and taxane based chemotherapy. Indeed, these signatures were independently predictive of chemotherapy response after adjusting for standard clinic-pathological variables such as age, grade, and estrogen receptor status in a cohort of 488 breast cancer patients treated with adriamycin and taxotere/taxol. Conclusions Importantly, our findings suggest the practicality of developing target based indices that predict response to therapeutics, as well as highlight the possibility of using gene signatures to guide the use of chemotherapy during treatment of breast cancer patients.

  14. The HLJ1-targeting drug screening identified Chinese herb andrographolide that can suppress tumour growth and invasion in non-small-cell lung cancer.

    Science.gov (United States)

    Lai, Yi-Hua; Yu, Sung-Liang; Chen, Hsuan-Yu; Wang, Chi-Chung; Chen, Huei-Wen; Chen, Jeremy J W

    2013-05-01

    HLJ1 is a novel tumour suppressor and is a potential druggable target for non-small-cell lung cancer (NSCLC). In this report, using a promoter-containing enhancer region as the HLJ1-targeting drug-screening platform, we identified several herbal compounds from a Chinese herbal bank with the capacity to enhance HLJ1 promoter activity and suppress tumour growth and invasion of NSCLC. Among the herbal drugs identified, the andrographolide (from Andrographis paniculata [Burm. f.] Nees.) most significantly induced HLJ1 expression and suppressed tumorigenesis both in vitro and in vivo. The andrographolide upregulates HLJ1 via JunB activation, which modulates AP-2α binding at the MMP-2 promoter and represses the expression of MMP-2. In addition, silencing of HLJ1 partially reverses the inhibition of cancer-cell invasion by andrographolide. Microarray transcriptomic analysis was performed to comprehensively depict the andrographolide-regulated signalling pathways. We showed that andrographolide can affect 939 genes (analysis of variance, false discovery rate andrographolide on anticancer invasion and proliferation. In conclusion, the HLJ1-targeting drug-screening platform is useful for screening of novel anticancer compounds. Using this platform, we identified andrographolide is a promising new anticancer agent that could suppress tumour growth and invasion in NSCLC.

  15. Younger age as a prognostic indicator in breast cancer: A cohort study

    LENUS (Irish Health Repository)

    Kheirelseid, Elrasheid A.H.

    2011-08-28

    Abstract Background The debate continues as to whether younger women who present with breast cancer have a more aggressive form of disease and a worse prognosis. The objectives of this study were to determine the incidence of breast cancer in women under 40 years old and to analyse the clinicopathological characteristics and outcome compared to an older patient cohort. Methods Data was acquired from a review of charts and the prospectively reviewed GUH Department of Surgery database. Included in the study were 276 women diagnosed with breast cancer under the age of forty and 2869 women over forty. For survival analysis each women less than 40 was matched with two women over forty for both disease stage and grade. Results The proportion of women diagnosed with breast cancer under the age of forty in our cohort was 8.8%. In comparison to their older counterparts, those under forty had a higher tumour grade (p = 0.044) and stage (p = 0.046), a lower incidence of lobular tumours (p < 0.001), higher estrogen receptor negativity (p < 0.001) and higher HER2 over-expression (p = 0.002); there was no statistical difference as regards tumour size (p = 0.477). There was no significant difference in overall survival (OS) for both groups; and factors like tumour size (p = 0.026), invasion (p = 0.026) and histological type (p = 0.027), PR (p = 0.031) and HER2 (p = 0.002) status and treatment received were independent predictors of OS Conclusion Breast cancer in younger women has distinct histopathological characteristics; however, this does not result in a reduced survival in this population.

  16. Younger age as a prognostic indicator in breast cancer: A cohort study

    International Nuclear Information System (INIS)

    H Kheirelseid, Elrasheid A; Boggs, Jennifer ME; Curran, Catherine; Glynn, Ronan W; Dooley, Cara; Sweeney, Karl J; Kerin, Michael J

    2011-01-01

    The debate continues as to whether younger women who present with breast cancer have a more aggressive form of disease and a worse prognosis. The objectives of this study were to determine the incidence of breast cancer in women under 40 years old and to analyse the clinicopathological characteristics and outcome compared to an older patient cohort. Data was acquired from a review of charts and the prospectively reviewed GUH Department of Surgery database. Included in the study were 276 women diagnosed with breast cancer under the age of forty and 2869 women over forty. For survival analysis each women less than 40 was matched with two women over forty for both disease stage and grade. The proportion of women diagnosed with breast cancer under the age of forty in our cohort was 8.8%. In comparison to their older counterparts, those under forty had a higher tumour grade (p = 0.044) and stage (p = 0.046), a lower incidence of lobular tumours (p < 0.001), higher estrogen receptor negativity (p < 0.001) and higher HER2 over-expression (p = 0.002); there was no statistical difference as regards tumour size (p = 0.477). There was no significant difference in overall survival (OS) for both groups; and factors like tumour size (p = 0.026), invasion (p = 0.026) and histological type (p = 0.027), PR (p = 0.031) and HER2 (p = 0.002) status and treatment received were independent predictors of OS Breast cancer in younger women has distinct histopathological characteristics; however, this does not result in a reduced survival in this population

  17. A database survey of equine tumours in the United Kingdom.

    Science.gov (United States)

    Knowles, E J; Tremaine, W H; Pearson, G R; Mair, T S

    2016-05-01

    Survey data on equine tumours are sparse compared with other species and may have changed over time. To describe the most frequently diagnosed equine tumours recorded by a diagnostic pathology laboratory over 29 years, to identify background factors associated with tumour type, and to identify any changes in the tumours diagnosed or the background of cases submitted during the study period. Observational; cross-sectional analysis of records of a diagnostic pathology laboratory. The records of all neoplastic equine histology submissions to the University of Bristol (January 1982-December 2010) were accessed from a database, and a list of diagnoses compiled. The 6 most commonly diagnosed tumour types were analysed using logistic regression to identify background factors associated with tumour type. The overall population of equine tumour submissions and the relative frequency of diagnosis of the most common tumour types were compared between decades. There were 964 cases included. The most frequently diagnosed tumours were: sarcoid (24% cases), squamous cell carcinoma (SCC) (19%), lymphoma (14%), melanoma (6%), gonadal stromal tumour (6%) and mast cell tumour (MCT) (4%). With sarcoid, Thoroughbred/Thoroughbred cross and gelding as reference categories: increasing age was significantly associated with the odds of each of the other tumour types, mares were at reduced risk of SCC, Arab/Arab cross had a higher risk of MCT, Cob/Cob cross had an increased risk of SCC and MCT, and ponies had an increased risk of melanoma. The mean age of submissions increased in each successive decade and the breed composition became broader. Sarcoids and lymphoma formed a smaller proportion of diagnoses in later decades. The types of tumours submitted to this laboratory have changed over the last 3 decades. Current data inform clinicians and researchers and further studies are warranted to follow trends. © 2015 EVJ Ltd.

  18. Benefits of the quality assured double and arbitration reading of mammograms in the early diagnosis of breast cancer in symptomatic women

    International Nuclear Information System (INIS)

    Waldmann, Annika; Katalinic, Alexander; Kapsimalakou, Smaragda; Grande-Nagel, Isabell; Barkhausen, Joerg; Vogt, Florian M.; Stoeckelhuber, Beate M.; Fischer, Dorothea

    2012-01-01

    To address the benefits of double and arbitration reading regarding tumour detection rates, percentage of in situ tumours, and number (of patients) needed to send for expert reading (number needed to treat; NNT) for one additional tumour finding. QuaMaDi is a quality assured breast cancer diagnosis programme; with two-view mammography (craniocaudal, mediolateral oblique) and, in case of breast density ACR 3 or 4, routine ultrasound imaging; and with independent double reading of all images. A consecutive sample of symptomatic women, i.e. women at risk for breast cancer, women aged 70 and above, and/or women with preceding BI-RADS III findings, was analysed. 28,558 mammograms were performed (mean age of women: 57.3 [standard deviation: 12.3] years). Discordant findings were present in 3,837 double readings and were sent for arbitration reading. After histopathological assessment, 52 carcinomas were found (thereof 32% in situ). These carcinomas accounted for 1.8 tumours per 1,000 examinations in the total cohort and increased the tumour detection rate up to 16.4/1,000. The NNT in discordant cases was 74. Double and arbitration reading appears to be a useful tool to ensure the quality of early detection of breast lesions in symptomatic women during indication-based, standardised mammography. circle Quality assured breast cancer diagnosis is feasible outside organised screening structures. (orig.)

  19. Regional variations in cancer survival: Impact of tumour stage, socioeconomic status, comorbidity and type of treatment in Norway.

    Science.gov (United States)

    Skyrud, Katrine Damgaard; Bray, Freddie; Eriksen, Morten Tandberg; Nilssen, Yngvar; Møller, Bjørn

    2016-05-01

    Cancer survival varies by place of residence, but it remains uncertain whether this reflects differences in tumour, patient and treatment characteristics (including tumour stage, indicators of socioeconomic status (SES), comorbidity and information on received surgery and radiotherapy) or possibly regional differences in the quality of delivered health care. National population-based data from the Cancer Registry of Norway were used to identify cancer patients diagnosed in 2002-2011 (n = 258,675). We investigated survival from any type of cancer (all cancer sites combined), as well as for the six most common cancers. The effect of adjusting for prognostic factors on regional variations in cancer survival was examined by calculating the mean deviation, defined by the mean absolute deviation of the relative excess risks across health services regions. For prostate cancer, the mean deviation across regions was 1.78 when adjusting for age and sex only, but decreased to 1.27 after further adjustment for tumour stage. For breast cancer, the corresponding mean deviations were 1.34 and 1.27. Additional adjustment for other prognostic factors did not materially change the regional variation in any of the other sites. Adjustment for tumour stage explained most of the regional variations in prostate cancer survival, but had little impact for other sites. Unexplained regional variations after adjusting for tumour stage, SES indicators, comorbidity and type of treatment in Norway may be related to regional inequalities in the quality of cancer care. © 2015 UICC.

  20. Parametric imaging of {sup 18}F-fluoro-3-deoxy-3-l-fluorothymidine PET data to investigate tumour heterogeneity

    Energy Technology Data Exchange (ETDEWEB)

    Veronese, M. [University of Padova, Department of Information Engineering (DEI), Padova (Italy); King' s College London, Department of Neuroimaging, Institute of Psychiatry, London (United Kingdom); Rizzo, G.; Bertoldo, A. [University of Padova, Department of Information Engineering (DEI), Padova (Italy); Aboagye, E.O. [Imperial College London, Comprehensive Cancer Imaging Centre, London (United Kingdom)

    2014-09-15

    [{sup 18}F]Fluoro-3'-deoxy-3'-l-fluorothymidine ([{sup 18}F]FLT) is a tissue proliferation marker which has been widely validated as a tumour-specific imaging tracer for PET. [{sup 18}F]FLT uptake in breast cancer is generally quantified at the region level or through first-order statistical descriptors (mean or maximum value), approaches that ignore the known complexity and heterogeneity of cancer tissues. Our aims were: (1) to validate a robust and reproducible voxel-wise approach to the quantification of [{sup 18}F]FLT PET data in breast cancer patients, and (2) to exploit the entire distribution of the [{sup 18}F]FLT retention estimates and their variability in the tumour region for the prediction of early treatment response. The dataset was derived from 15 patients with stage II-IV breast cancer, scanned twice before chemotherapy and once 1 week after therapy. Using RECIST criteria (after 60 days) nine patients were categorized as responders or nonresponders to treatment. Kinetic modelling (compartmental modelling, Patlak analysis and spectral analysis with iterative filter), tissue-to-plasma ratio and standardized uptake value were applied at the voxel level. Test-retest estimates were used to assess reproducibility and reliability of the [{sup 18}F]FLT uptake values before and after therapy for responder/nonresponder prediction. All the methods provided a measure of [{sup 18}F]FLT uptake that was reliable and reproducible with ICC >0.94. Moreover, a very strong correlation was found among the methods (R {sup 2} > 0.81). All the methods provided a limited number of outliers (<20 % in tumour), with the exception of compartmental modelling (>25 %) which was therefore excluded from the prediction analysis. Differences between before and after therapy in mean voxel-wise uptake in tumour did not allow a complete responder/nonresponder classification. In contrast, considering the full estimate distributions within the tumour (changes in median and mode

  1. Presence of papillomavirus sequences in condylomatous lesions of the mamillae and in invasive carcinoma of the breast

    International Nuclear Information System (INIS)

    Villiers, Ethel-Michele de; Sandstrom, Robert E; Hausen, Harald zur; Buck, Charles E

    2005-01-01

    Viruses including Epstein–Barr virus (EBV), a human equivalent of murine mammary tumour virus (MMTV) and human papillomavirus (HPV) have been implicated in the aetiology of human breast cancer. We report the presence of HPV DNA sequences in areolar tissue and tumour tissue samples from female patients with breast carcinoma. The presence of virus in the areolar–nipple complex suggests to us a potential pathogenic mechanism. Polymerase chain reaction (PCR) was undertaken to amplify HPV types in areolar and tumour tissue from breast cancer cases. In situ hybridisation supported the PCR findings and localised the virus in nipple, areolar and tumour tissue. Papillomavirus DNA was present in 25 of 29 samples of breast carcinoma and in 20 of 29 samples from the corresponding mamilla. The most prevalent type in both carcinomas and nipples was HPV 11, followed by HPV 6. Other types detected were HPV 16, 23, 27 and 57 (nipples and carcinomas), HPV 20, 21, 32, 37, 38, 66 and GA3-1 (nipples only) and HPV 3, 15, 24, 87 and DL473 (carcinomas only). Multiple types were demonstrated in seven carcinomas and ten nipple samples. The data demonstrate the occurrence of HPV in nipple and areolar tissues in patients with breast carcinoma. The authors postulate a retrograde ductular pattern of viral spread that may have pathogenic significance

  2. Hypoxia and loss of PHD2 inactivate stromal fibroblasts to decrease tumour stiffness and metastasis

    DEFF Research Database (Denmark)

    Madsen, Chris D; Pedersen, Jesper Thorhauge; Venning, Freja A

    2015-01-01

    , which can be prevented by simultaneous depletion of HIF-1α. Treatment with the PHD inhibitor DMOG in an orthotopic breast cancer model significantly decreases spontaneous metastases to the lungs and liver, associated with decreased tumour stiffness and fibroblast activation. PHD2 depletion in CAFs co......-injected with tumour cells similarly prevents CAF-induced metastasis to lungs and liver. Our data argue that reversion of CAFs towards a less active state is possible and could have important clinical implications....

  3. Evaluation of implanted gold seeds for breast radiotherapy planning and on treatment verification: A feasibility study on behalf of the IMPORT trialists

    International Nuclear Information System (INIS)

    Coles, Charlotte E.; Harris, Emma J.; Donovan, Ellen M.; Bliss, Peter; Evans, Philip M.; Fairfoul, Jamie; Mackenzie, Christine; Rawlings, Christine; Syndikus, Isabel; Twyman, Nicola; Vasconcelos, Joana; Vowler, Sarah L.; Wilkinson, Jenny S.; Wilks, Robin; Wishart, Gordon C.; Yarnold, John

    2011-01-01

    Background and purpose: We describe a feasibility study testing the use of gold seeds for the identification of post-operative tumour bed after breast conservation surgery (BCS). Materials and Methods: Fifty-three patients undergoing BCS for invasive cancer were recruited. Successful use was defined as all six seeds correctly positioned around the tumour bed during BCS, unique identification of all implanted seeds on CT planning scan and ≥3 seeds uniquely identified at verification to give couch displacement co-ordinates in 10/15 fractions. Planning target volume (PTV) margin size for four correction strategies were calculated from these data. Variability in tumour bed contouring was investigated with five radiation oncologists outlining five CT datasets. Results: Success in inserting gold seeds, identifying them at CT planning and using them for on-treatment verification was recorded in 45/51 (88%), 37/38 (97%) and 42/43 (98%) of patients, respectively. The clinicians unfamiliar with CT breast planning consistently contoured larger volumes than those already trained. Margin size ranged from 10.1 to 1.4 mm depending on correction strategy. Conclusion: It is feasible to implant tumour bed gold seeds during BCS. Whilst taking longer to insert than surgical clips, they have the advantage of visibility for outlining and verification regardless of the ionising radiation beam quality. Appropriate correction strategies enable margins of the order of 5 mm as required by the IMPORT trials however, tackling clinician variability in contouring is important.

  4. Upregulation of Mrps18a in breast cancer identified by selecting phage antibody libraries on breast tissue sections

    DEFF Research Database (Denmark)

    Sørensen, Karen Marie Juul; Meldgaard, Theresa; Melchjorsen, Connie Jenning

    2017-01-01

    BACKGROUND: One of the hallmarks of cancer is an altered energy metabolism, and here, mitochondria play a central role. Previous studies have indicated that some mitochondrial ribosomal proteins change their expression patterns upon transformation. METHOD: In this study, we have used the selection...... of recombinant antibody libraries displayed on the surface of filamentous bacteriophage as a proteomics discovery tool for the identification of breast cancer biomarkers. A small subpopulation of breast cells expressing both cytokeratin 19 and cytokeratin 14 was targeted using a novel selection procedure....... RESULTS: We identified the mitochondrial ribosomal protein s18a (Mrps18a) as a protein which is upregulated in breast cancer. However, Mrps18a was not homogeneously upregulated in all cancer cells, suggesting the existence of sub-populations within the tumor. The upregulation was not confined...

  5. Limbic encephalitis and antibodies to Ma2: a paraneoplastic presentation of breast cancer.

    Science.gov (United States)

    Sutton, I; Winer, J; Rowlands, D; Dalmau, J

    2000-08-01

    A patient with atypical medullary breast cancer is described who presented with symptoms of limbic encephalitis. The patient's serum and CSF contained antibodies that reacted with the nervous system and the tumour. These antibodies recognised Ma2, a neuronal protein related to paraneoplastic limbic and brainstem encephalitis in men with testicular tumours. This report highlights the importance of testing for paraneoplastic antineuronal antibodies in cases of unexplained limbic encephalitis and suggests screening for breast cancer in women with antibodies predominantly directed to Ma2.

  6. Factors influencing survival and recurrence-free intervals after treatment of primary breast cancer

    International Nuclear Information System (INIS)

    O'Higgins, N.; Brady, H.R.; Clark, C.G.

    1984-01-01

    A retrospective analysis of 739 patients with breast cancer is presented. Factors influencing overall survival, recurrence-free interval and survival after first recurrence are analysed and discussed. None of the factors was affected by age or menopausal status at the time of presentation. Overall survival and recurrence-free intervals varied significantly with tumour size, extent of nodal spread and tumour site. Medially situated tumours, large tumours and extensive nodal spread were associated with earlier first recurrence and poor prognosis. No difference in survival or recurrence-free interval was observed between different surgical operations. Although overall survival was longer in patients who received post-operative radiotherapy, no significant differences in survival or disease-free intervals were noted when patients were standardised for operation or tumour stage. Survival after local recurrence was longer than survival after distant metastases, although the time of onset of local and distant disease followed an identical pattern. These results suggest that the tumour characteristics of size, site and nodal spread are important determinants of survival and recurrence-free interval in primary breast cancer. Local recurrence should be regarded as a manifestation of systemic disease. (author)

  7. A novel gene expression signature for bone metastasis in breast carcinomas

    NARCIS (Netherlands)

    Savci-Heijink, C. Dilara; Halfwerk, Hans; Koster, Jan; van de Vijver, Marc J.

    2016-01-01

    Metastatic cancer remains the leading cause of death for patients with breast cancer. To understand the mechanisms underlying the development of distant metastases to specific sites is therefore important and of potential clinical value. From 157 primary breast tumours of the patients with known

  8. Demographic pattern of male breast cancer: an institutional based study

    International Nuclear Information System (INIS)

    Tanseem, S.; Khan, M.M.; Khan, M.M.K.

    2011-01-01

    Background: Male breast cancer incidence rises with age with peak in the sixth and seventh decade. It is one of the rare diseases and accounts for less than 1% of all malignancies worldwide. It is usually diagnosed in the late stage with poor prognosis. Objective: The purpose of this study was to know the demographic pattern and tumour characteristic of breast cancer in men reported at Institute of Radiotherapy and Nuclear Medicine (IRNUM), Peshawar. Methods: Retrospective data was collected from the (IRNUM), Peshawar for a period of three years (2006-2008). The evaluation was done from the histopathological reports of mastectomy and biopsy specimens. All male patients in the age group 26 -86 year with breast cancer were included in the study. The age of the patients and tumour characteristics recorded were size, grade, type, skin involvement and stage. Results: Total number of male patients with breast cancer were 31 (2.1%) out of the total patients with breast malignancy during the study period with the mean age of 58.3 years. Tumour size ranged from 2 to 12 Cm. with average of 3.6 Cm. Invasive ductal carcinoma was found in 87% , papillary carcinoma in 6.5%, each of malignant fibrous histocytoma and sarcoma in 3.2% cases. Maximum number of patients was of grade II (41%). Patients in whom stage of the disease was know n were 22 cases with 45.5% had stage III disease and 32% had stage IV disease. Skin involvement was found positive in 8 (25.8%). Conclusion: Due to poor health care system breast cancer is diagnosed in a late stage of the disease and prognosis is poor. (author)

  9. The prognostic value of temporal in vitro and in vivo derived hypoxia gene-expression signatures in breast cancer

    International Nuclear Information System (INIS)

    Starmans, Maud H.W.; Chu, Kenneth C.; Haider, Syed; Nguyen, Francis; Seigneuric, Renaud; Magagnin, Michael G.; Koritzinsky, Marianne; Kasprzyk, Arek; Boutros, Paul C.; Wouters, Bradly G.

    2012-01-01

    Background and purpose: Recent data suggest that in vitro and in vivo derived hypoxia gene-expression signatures have prognostic power in breast and possibly other cancers. However, both tumour hypoxia and the biological adaptation to this stress are highly dynamic. Assessment of time-dependent gene-expression changes in response to hypoxia may thus provide additional biological insights and assist in predicting the impact of hypoxia on patient prognosis. Materials and methods: Transcriptome profiling was performed for three cell lines derived from diverse tumour-types after hypoxic exposure at eight time-points, which include a normoxic time-point. Time-dependent sets of co-regulated genes were identified from these data. Subsequently, gene ontology (GO) and pathway analyses were performed. The prognostic power of these novel signatures was assessed in parallel with previous in vitro and in vivo derived hypoxia signatures in a large breast cancer microarray meta-dataset (n = 2312). Results: We identified seven recurrent temporal and two general hypoxia signatures. GO and pathway analyses revealed regulation of both common and unique underlying biological processes within these signatures. None of the new or previously published in vitro signatures consisting of hypoxia-induced genes were prognostic in the large breast cancer dataset. In contrast, signatures of repressed genes, as well as the in vivo derived signatures of hypoxia-induced genes showed clear prognostic power. Conclusions: Only a subset of hypoxia-induced genes in vitro demonstrates prognostic value when evaluated in a large clinical dataset. Despite clear evidence of temporal patterns of gene-expression in vitro, the subset of prognostic hypoxia regulated genes cannot be identified based on temporal pattern alone. In vivo derived signatures appear to identify the prognostic hypoxia induced genes. The prognostic value of hypoxia-repressed genes is likely a surrogate for the known importance of

  10. Developing Anti-HER2 Vaccines: Breast Cancer Experience.

    Science.gov (United States)

    Al-Awadhi, Aydah; Murray, James Lee; Ibrahim, Nuhad K

    2018-04-25

    Breast cancer accounts for more than one million new cases annually and is the leading cause of death in women globally. HER2 overexpression induces cellular and humoral immune responses against the HER2 protein and is associated with higher tumour proliferation rates. Trastuzumab-based therapies are effectively and widely used as standard of care in HER2-amplified/overexpressed breast cancer patients; one cited mechanism of action is the induction of passive immunity and antibody-dependent cellular cytotoxicity against malignant breast cancer cells. These findings drove the efforts to generate antigen-specific immunotherapy to trigger the patient's immune system to target HER2-overexpressing tumour cells, which led to the development of various vaccines against the HER2 antigen. This manuscript discusses the various anti-HER2 vaccine formulations and strategies and their potential role in the metastatic and adjuvant settings. This article is protected by copyright. All rights reserved. © 2018 UICC.

  11. In Vivo Detection of HSP90 Identifies Breast Cancers with Aggressive Behavior.

    Science.gov (United States)

    Osada, Takuya; Kaneko, Kensuke; Gwin, William R; Morse, Michael A; Hobeika, Amy; Pogue, Brian W; Hartman, Zachary C; Hughes, Philip F; Haystead, Timothy; Lyerly, H Kim

    2017-12-15

    Purpose: Hsp90, a chaperone to numerous molecular pathways in malignant cells, is elevated in aggressive breast cancers. We hypothesized that identifying breast cells with elevated Hsp90 activity in situ could result in early detection of aggressive breast cancers. Experimental Design: We exploited the uptake of an Hsp90 inhibitor by malignant cells to create an imaging probe (HS131) of Hsp90 activity by linking it to a near-infrared (nIR) dye. HS131 uptake into cells correlated with cell membrane expression of Hsp90 and was used to image molecular subtypes of murine and human breast cancers in vitro and in murine models. Results: HS131 imaging was both sensitive and specific in detecting the murine 4T1 breast cancer cell line, as well as subclones with differing metastatic potential. Highly metastatic subclones (4T07) had high HS131 uptake, but subclones with lower metastatic potential (67NR, 168FARN) had low HS131 uptake. We generated isogenic cell lines to demonstrate that overexpression of a variety of specific oncogenes resulted in high HS131 uptake and retention. Finally, we demonstrated that HS131 could be used to detect spontaneous tumors in MMTV-neu mice, as well as primary and metastatic human breast cancer xenografts. HS131 could image invasive lobular breast cancer, a histologic subtype of breast cancer which is often undetectable by mammography. Conclusions: An HSP90-targeting nIR probe is sensitive and specific in imaging all molecular subtypes of murine and human breast cancer, with higher uptake in aggressive and highly metastatic clones. Clinical studies with Hsp90-targeting nIR probes will be initiated shortly. Clin Cancer Res; 23(24); 7531-42. ©2017 AACR . ©2017 American Association for Cancer Research.

  12. Prolactin, TNF alpha and nitric oxide expression in nitroso-N-methylurea-induced-mammary tumours

    Directory of Open Access Journals (Sweden)

    Vegh Irene

    2007-11-01

    Full Text Available Abstract Background The N-Nitrosomethylurea breast cancer model induced in rats is used for the study of carcinogenesis in mammary cancer, prostate, pancreas, etc. This model is very similar to human neoplastic disease. Methods The present experimental study was designed to assess whether metoclopramide administration has any effect on development of MNU-induced tumours, and evaluate the treatment of goserelin acetate on PRL, TNF alpha and NO expression. NMU was administered to female Wistar rats on 2 occasions (5 mg/100 g body w/rat. PRL and TNF alpha were performed by immune-assay. Nitric Oxide by semi automated-assay and ploidy analyses by flow cytometry. Results The administration of metoclopramide made the induction time shorter and increased the incidence and average of tumours per rat. Tumours development was inhibited by a goserelin chronic administration. The ploidy of adenocarcinoma was polyploid-aneuploid type (average S = 60%. It was higher basal PRL plasma levels in rats with NMU induced tumours than in basal controls without tumour (p Conclusion The increase of blood PRL levels in NMU-induced rats may be an indicator of a poor prognosis of mammary cancer evolution. The metoclopramide administration accelerates tumour growth. However goserelin administration achieves regression in tumour development associated to inhibition PRL, TNF alpha and NO expression.

  13. Primary lymphoma of the breast involving both axillae with bilateral breast carcinoma

    Directory of Open Access Journals (Sweden)

    Rubin Gary

    2008-05-01

    Full Text Available Abstract Background Primary Non-Hodgkin's Lymphoma (PHNL of the breast is a rare entity, while secondary involvement of the breast with diffuse disease of Non-Hodgkin's lymphoma (NHL is more common. However, PNHL is the most frequent haematopoietic tumour of the breast. Diagnostic criteria for PNHL of the breast are presence of technically adequate pathologic specimens, close association of mammary tissue and lymphomatous infiltrate, no prior diagnosis of an extarammamary lymphoma, and no evidence of concurrent widespread disease, except for ipsilateral axillary lymph nodes if concomitant with the primary lesion. Case presentation A 57-year-old woman was recalled because her screening mammograms revealed three separate lesions in her right breast and one in the left. Histology of the lesions confirmed lymphoma in one breast with ductal carcinoma in the other. Conclusion Most of reported cases in literature have been involving the right breast, and almost all the patients were females. NHLs of the breast typically present as unilateral mass; the frequency of bilateral disease at first presentation ranges from 5–25%. Our objective is to report a case of primary lymphoma of the breast involving both axillae with concomitant bilateral primary breast cancer which has not been reported yet to our best of knowledge in literature.

  14. Do clinical, histological or immunohistochemical primary tumour characteristics translate into different {sup 18}F-FDG PET/CT volumetric and heterogeneity features in stage II/III breast cancer?

    Energy Technology Data Exchange (ETDEWEB)

    Groheux, David; Martineau, Antoine; Merlet, Pascal [Saint-Louis Hospital, Department of Nuclear Medicine, Paris (France); Majdoub, Mohamed; Hatt, Mathieu; Visvikis, Dimitris [INSERM, UMR 1101 LaTIM, Brest (France); Tixier, Florent; Le Rest, Catherine Cheze [Miletrie Hospital, DACTIM, Department of Nuclear Medicine, Poitiers (France); Espie, Marc [Saint-Louis Hospital, Breast Diseases Unit and Department of Medical Oncology, Paris (France); Roquancourt, Anne de [Saint-Louis Hospital, Department of Pathology, Paris (France); Hindie, Elif [University of Bordeaux, Department of Nuclear Medicine, CHU Bordeaux, Bordeaux (France)

    2015-10-15

    The aim of this retrospective study was to determine if some features of baseline {sup 18}F-FDG PET images, including volume and heterogeneity, reflect clinical, histological or immunohistochemical characteristics in patients with stage II or III breast cancer (BC). Included in the present retrospective analysis were 171 prospectively recruited patients with stage II/III BC treated consecutively at Saint-Louis hospital. Primary tumour volumes were semiautomatically delineated on pretreatment {sup 18}F-FDG PET images. The parameters extracted included SUV{sub max}, SUV{sub mean}, metabolically active tumour volume (MATV), total lesion glycolysis (TLG) and heterogeneity quantified using the area under the curve of the cumulative histogram and textural features. Associations between clinical/histopathological characteristics and {sup 18}F-FDG PET features were assessed using one-way analysis of variance. Areas under the ROC curves (AUC) were used to quantify the discriminative power of the features significantly associated with clinical/histopathological characteristics. T3 tumours (>5 cm) exhibited higher textural heterogeneity in {sup 18}F-FDG uptake than T2 tumours (AUC <0.75), whereas there were no significant differences in SUV{sub max} and SUV{sub mean}. Invasive ductal carcinoma showed higher SUV{sub max} values than invasive lobular carcinoma (p = 0.008) but MATV, TLG and textural features were not discriminative. Grade 3 tumours had higher FDG uptake (AUC 0.779 for SUV{sub max} and 0.694 for TLG), and exhibited slightly higher regional heterogeneity (AUC 0.624). Hormone receptor-negative tumours had higher SUV values than oestrogen receptor-positive (ER-positive) and progesterone receptor-positive tumours, while heterogeneity patterns showed only low-level variation according to hormone receptor expression. HER-2 status was not associated with any of the image features. Finally, SUV{sub max}, SUV{sub mean} and TLG significantly differed among the three

  15. Interleukin-2 and its receptor complex (α, β and γ chains) in in situ and infiltrative human breast cancer: an immunohistochemical comparative study

    International Nuclear Information System (INIS)

    García-Tuñnón, Ignacio; Ricote, Mónica; Ruiz, Antonio; Fraile, Benito; Paniagua, Ricardo; Royuela, Mar

    2004-01-01

    The presence and distribution of interleukin-2 (IL-2) and its receptor complex (Rα, Rβ, Rγ) were studied in 52 women who were clinically and histopathologically diagnosed with breast tumours (17 in situ and 35 infiltrating), and in 13 women with benign fibrocystic lesions in the breast. Immunohistochemistry with antibodies against IL-2, IL-2Rα, IL-2Rβ and IL-2Rγ was used. A comparative semiquantitative immunohistochemical study between the three breast groups (fibrocystic lesions, in situ tumours and infiltrating tumours) was performed. IL-2 and its three receptor chains were immunodetected in the cytoplasm of epithelial cells. The three receptor chains were also detected on the cell surface. In fibrocystic lesions, immunoreactions to IL-2 (38.5% of cases), IL-2Rα (53.8%) and IL-2Rβ (30.8%) were very weak, whereas immunoreaction to IL-2Rγ (46.1%) was somewhat more intense. In in situ tumours, the percentages of cases that immunostained positively for IL-2 and its three receptor chains were similar to those observed in fibrocystic lesions, but immunostainings of the four antibodies were more intense. In infiltrative tumours, the percentages of positively stained cases and also immunostaining intensities were approximately twice that found for in situ tumours. Within infiltrating tumours, the percentage of cases showing immunoreaction to IL-2 and their three receptor chains was higher in the patients with lymph node infiltration at the time of surgery. The development of breast tumour is associated with an increased expression of IL-2 and its three receptor chains, and this expression also seems to be associated with the malignancy of the tumour

  16. Cooperative tumour cell membrane targeted phototherapy

    Science.gov (United States)

    Kim, Heegon; Lee, Junsung; Oh, Chanhee; Park, Ji-Ho

    2017-06-01

    The targeted delivery of therapeutics using antibodies or nanomaterials has improved the precision and safety of cancer therapy. However, the paucity and heterogeneity of identified molecular targets within tumours have resulted in poor and uneven distribution of targeted agents, thus compromising treatment outcomes. Here, we construct a cooperative targeting system in which synthetic and biological nanocomponents participate together in the tumour cell membrane-selective localization of synthetic receptor-lipid conjugates (SR-lipids) to amplify the subsequent targeting of therapeutics. The SR-lipids are first delivered selectively to tumour cell membranes in the perivascular region using fusogenic liposomes. By hitchhiking with extracellular vesicles secreted by the cells, the SR-lipids are transferred to neighbouring cells and further spread throughout the tumour tissues where the molecular targets are limited. We show that this tumour cell membrane-targeted delivery of SR-lipids leads to uniform distribution and enhanced phototherapeutic efficacy of the targeted photosensitizer.

  17. Survival of women with locally advanced breast cancer at a teaching hospital in Lahore

    International Nuclear Information System (INIS)

    Iqbal, J.; Bano, K.; Saeed, A.; Akram, M.; Aziz, Z.

    2010-01-01

    To correlate the clinical features of women presenting with locally advanced breast cancer with event-free survival (EFS) and overall survival (OS) and to evaluate the patterns of relapse. Methods: A total of 200 patients presenting consecutively over 9 years with Stage III breast cancer were evaluated for age, socio-economic status (SES), tumour size and grade, number of involved lymph nodes, stage III sub-categories, estrogen and progesterone receptor (ER/PR) status, treatment profiles and responses, and sites of relapse. EFS and OS at 5 and 10 years were calculated. Results: Median age was 45 years. Poorly differentiated tumours were found in 127 patients, while 128 had larger tumours (T3 and T4). Eighty women had extensive nodal involvement (N2 and N3), and 86 had Stage IIIA tumours. Chemotherapy was given to 44 patients before surgery and one of these patients achieved pathological complete response. At 5 and 10 years, EFS was 25% and 7%, and OS was 52% and 31%, respectively. By Cox regression analysis, significant predictors of EFS included tumour size (95% CI 1.14-1.72), nodal involvement (95% CI 1.06-1.59) and ER/PR positive tumours (95% CI 1.08-2.29). Predictors of OS included nodal involvement (95% CI 0.98-3.3) and ER/PR positive tumours (95% CI 1.08-2.29). No patient in stage IIIC was alive at 10 years. Loco-regional disease was the most common site of relapse (28.5%). Conclusions: Locally advance breast cancer at our centre is associated with poor survival, and most patients relapsed by 5 years. (author)

  18. Plasma soluble cluster of differentiation 147 levels are increased in breast cancer patients and associated with lymph node metastasis and chemoresistance.

    Science.gov (United States)

    Kuang, Y H; Liu, Y J; Tang, L L; Wang, S M; Yan, G J; Liao, L Q

    2018-05-25

    Cluster of differentiation 147 (CD147) contributes to breast cancer invasion, metastasis, and multidrug resistance. Recent studies have shown that peripheral soluble CD147 (sCD147) is increased in hepatocellular tumour and multiple myeloma patients and correlated with disease severity. The primary aim of our study was to assess the level, as well as the biological and clinical significance of sCD147 in breast cancer. We tested plasma sCD147 levels in 308 breast cancer patients by enzyme-linked immunosorbent assay between February 2014 and February 2017. A subset of 165 cases of benign breast diseases was included as a control group at the same period. We analysed the clinical significance of plasma sCD147 with relevance to clinicopathological factors of breast cancer patients. Plasma sCD147 levels were significantly higher in patients with primary breast cancer than those with benign breast diseases (P=0.001), in patients with locally advanced breast cancer (T3-T4 tumour) than those in early breast cancer (T1-T2 tumour; P=0.001), in patients with lymph node metastasis than in those without (P<0.001), and in patients with high recurrence risk than those with medium recurrence risk (P<0.001). Plasma sCD147 levels were also significantly higher in the chemotherapy-resistant group than in the chemotherapy-sensitive group (P=0.040). Plasma sCD147 was an independent predictor for lymph node metastasis in breast cancer patients (P=0.001). This is the first study to demonstrate that plasma sCD147 levels are elevated in breast cancer patients. Soluble CD147 is also associated with tumour size, lymph node metastasis, high recurrent risk, and chemoresistance. Our findings support that plasma sCD147 is an independent predictive factor for lymph node metastasis.

  19. Endogenous myoglobin in human breast cancer is a hallmark of luminal cancer phenotype.

    Science.gov (United States)

    Kristiansen, G; Rose, M; Geisler, C; Fritzsche, F R; Gerhardt, J; Lüke, C; Ladhoff, A-M; Knüchel, R; Dietel, M; Moch, H; Varga, Z; Theurillat, J-P; Gorr, T A; Dahl, E

    2010-06-08

    We aimed to clarify the incidence and the clinicopathological value of non-muscle myoglobin (Mb) in a large cohort of non-invasive and invasive breast cancer cases. Matched pairs of breast tissues from 10 patients plus 17 breast cell lines were screened by quantitative PCR for Mb mRNA. In addition, 917 invasive and 155 non-invasive breast cancer cases were analysed by immunohistochemistry for Mb expression and correlated to clinicopathological parameters and basal molecular characteristics including oestrogen receptor-alpha (ERalpha)/progesteron receptor (PR)/HER2, fatty acid synthase (FASN), hypoxia-inducible factor-1alpha (HIF-1alpha), HIF-2alpha, glucose transporter 1 (GLUT1) and carbonic anhydrase IX (CAIX). The spatial relationship of Mb and ERalpha or FASN was followed up by double immunofluorescence. Finally, the effects of estradiol treatment and FASN inhibition on Mb expression in breast cancer cells were analysed. Myoglobin mRNA was found in a subset of breast cancer cell lines; in microdissected tumours Mb transcript was markedly upregulated. In all, 71% of tumours displayed Mb protein expression in significant correlation with a positive hormone receptor status and better prognosis. In silico data mining confirmed higher Mb levels in luminal-type breast cancer. Myoglobin was also correlated to FASN, HIF-2alpha and CAIX, but not to HIF-1alpha or GLUT1, suggesting hypoxia to participate in its regulation. Double immunofluorescence showed a cellular co-expression of ERalpha or FASN and Mb. In addition, Mb levels were modulated on estradiol treatment and FASN inhibition in a cell model. We conclude that in breast cancer, Mb is co-expressed with ERalpha and co-regulated by oestrogen signalling and can be considered a hallmark of luminal breast cancer phenotype. This and its possible new role in fatty acid metabolism may have fundamental implications for our understanding of Mb in solid tumours.

  20. Breast cancer survival and season of surgery

    DEFF Research Database (Denmark)

    Teilum, Dorthe; Bjerre, Karsten D; Tjønneland, Anne M

    2012-01-01

    Background Vitamin D has been suggested to influence the incidence and prognosis of breast cancer, and studies have found better overall survival (OS) after diagnosis for breast cancer in summer-autumn, where the vitamin D level are expected to be highest. Objective To compare the prognostic...... outcome for early breast cancer patients operated at different seasons of the year. Design Open population-based cohort study. Setting Danish women operated 1978-2010. Cases 79 658 adjusted for age at surgery, period of surgery, tumour size, axillary lymph node status and hormone receptor status...

  1. Neurohypophysis granular cell tumours. Upon neurohypophysis rare tumours

    International Nuclear Information System (INIS)

    Barrande, G.; Kujas, M.; Gancel, A.; Turpin, G.; Bruckert, E.; Kuhn, J.M.; Luton, J.P.

    1995-01-01

    Granular cell tumours of neurohypophysis are rare. These tumours are more often encountered as incidental autopsy findings seen in up to 17 % of unselected adult autopsy cases. There are few reports of para-sellar granular cell tumours large enough to cause symptoms. We present three cases of neurohypophysis granular cell tumour and a review of the literature. In one patient, the asymptomatic granular cell tumour was incidentally discovered at surgical removal of a corticotrophic micro-adenoma. The remaining 2 patients had a symptomatic tumour which caused neurological symptoms such as visual disturbance and headaches and endocrine disorders such as hypopituitarism or hyper-prolactinaemia. In these 2 cases, computerized tomography showed a well-circumscribed, contrast-enhanced, intra-sellar and supra-sellar mass. Magnetic resonance imaging demonstrated an isointense gadolinium-enhanced mass in T1-weighted-images. Trans-sphenoidal partial resection was performed and histology was interpreted as a granular cell tumour. The immunohistochemical study was positive for glial fibrillary acidic protein (GEAP) and neuron specific enolase (NSE) in 1 of the 2 tumours and positive for S100 protein and vimentin in both tumours but negative for CD68. The histogenesis of neurohypophysis granular cell tumours is still controversial but ultrastructural and immunohistochemical studies support the theory that may arise from pituicytes, the glial cells of neurohypophysis. Management of these benign, slow growing, tumours is based mainly on neurosurgical resection. Data from the literature do not support a beneficial effect of post operative radiation therapy on postoperative recurrences. (authors). 23 refs., 4 figs., 1 tab

  2. MRI texture analysis in differentiating luminal A and luminal B breast cancer molecular subtypes - a feasibility study.

    Science.gov (United States)

    Holli-Helenius, Kirsi; Salminen, Annukka; Rinta-Kiikka, Irina; Koskivuo, Ilkka; Brück, Nina; Boström, Pia; Parkkola, Riitta

    2017-12-29

    The aim of this study was to use texture analysis (TA) of breast magnetic resonance (MR) images to assist in differentiating estrogen receptor (ER) positive breast cancer molecular subtypes. Twenty-seven patients with histopathologically proven invasive ductal breast cancer were selected in preliminary study. Tumors were classified into molecular subtypes: luminal A (ER-positive and/or progesterone receptor (PR)-positive, human epidermal growth factor receptor type 2 (HER2) -negative, proliferation marker Ki-67 MaZda. Texture parameters and tumour volumes were correlated with tumour prognostic factors. Textural differences were observed mainly in precontrast images. The two most discriminative texture parameters to differentiate luminal A and luminal B subtypes were sum entropy and sum variance (p = 0.003). The AUCs were 0.828 for sum entropy (p = 0.004), and 0.833 for sum variance (p = 0.003), and 0.878 for the model combining texture features sum entropy, sum variance (p = 0.001). In the LOOCV, the AUC for model combining features sum entropy and sum variance was 0.876. Sum entropy and sum variance showed positive correlation with higher Ki-67 index. Luminal B types were larger in volume and moderate correlation between larger tumour volume and higher Ki-67 index was also observed (r = 0.499, p = 0.008). Texture features which measure randomness, heterogeneity or smoothness and homogeneity may either directly or indirectly reflect underlying growth patterns of breast tumours. TA and volumetric analysis may provide a way to evaluate the biologic aggressiveness of breast tumours and provide aid in decisions regarding therapeutic efficacy.

  3. Identifying women with dense breasts at high risk for interval cancer: a cohort study.

    Science.gov (United States)

    Kerlikowske, Karla; Zhu, Weiwei; Tosteson, Anna N A; Sprague, Brian L; Tice, Jeffrey A; Lehman, Constance D; Miglioretti, Diana L

    2015-05-19

    Twenty-one states have laws requiring that women be notified if they have dense breasts and that they be advised to discuss supplemental imaging with their provider. To better direct discussions of supplemental imaging by determining which combinations of breast cancer risk and Breast Imaging Reporting and Data System (BI-RADS) breast density categories are associated with high interval cancer rates. Prospective cohort. Breast Cancer Surveillance Consortium (BCSC) breast imaging facilities. 365,426 women aged 40 to 74 years who had 831,455 digital screening mammography examinations. BI-RADS breast density, BCSC 5-year breast cancer risk, and interval cancer rate (invasive cancer ≤12 months after a normal mammography result) per 1000 mammography examinations. High interval cancer rate was defined as more than 1 case per 1000 examinations. High interval cancer rates were observed for women with 5-year risk of 1.67% or greater and extremely dense breasts or 5-year risk of 2.50% or greater and heterogeneously dense breasts (24% of all women with dense breasts). The interval rate of advanced-stage disease was highest (>0.4 case per 1000 examinations) among women with 5-year risk of 2.50% or greater and heterogeneously or extremely dense breasts (21% of all women with dense breasts). Five-year risk was low to average (0% to 1.66%) for 51.0% of women with heterogeneously dense breasts and 52.5% with extremely dense breasts, with interval cancer rates of 0.58 to 0.63 and 0.72 to 0.89 case per 1000 examinations, respectively. The benefit of supplemental imaging was not assessed. Breast density should not be the sole criterion for deciding whether supplemental imaging is justified because not all women with dense breasts have high interval cancer rates. BCSC 5-year risk combined with BI-RADS breast density can identify women at high risk for interval cancer to inform patient-provider discussions about alternative screening strategies. National Cancer Institute.

  4. Contribution of 18-FDG-PET/TC in the handling of the locally advanced stadiums of breast cancer

    International Nuclear Information System (INIS)

    Azar, M.; Cresta Morgado, C.; Noblia, C.; Gonzalez, E.; Armanasco, E.; Montoya, D.; Ipina, M.; Gorostidy, A.; Alvarez, A.; Mickiewicz, E.; Bruno, G.; Gonzalez, C.; Parma, P.; Blumenkrantz, Y.

    2010-01-01

    Conventional imaging modalities provide only morphological details and do not provide information on the metabolic status of a lesion, which is very important in differentiating a benign from a malignant lesion. Early diagnosis and reliable imaging assessment of response to treatment are essential in the clinical management of breast cancer. Positron Emission Tomography (PET) has been widely shown to be highly useful for the diagnosis of palpable masses, for staging, for obtaining long-term prognostic information, and for demonstrating tumour response to chemotherapy at an early phase or after completion of treatment in patient with breast cancer. Twenty-three consecutive female patients with primary breast carcinoma (T3/T4,N2,M0) were prospectively recruited for AT--TDG and tumour 18F-IDG update (standardized update value, SUV was used as a metabolic indicator. There was a positive relationship between tumour metabolic and response to chemotherapy and pathological conditions SUV provides an index of regional tracer uptake and a reduced SUV are indicative of tumour regression. (authors) [es

  5. Review article: Pathogenesis and management of gastric carcinoid tumours.

    Science.gov (United States)

    Burkitt, M D; Pritchard, D M

    2006-11-01

    Gastric carcinoid tumours are rare, but are increasing in incidence. To discuss tumour pathogenesis and outline current approaches to patient management. Review of published articles following a Pubmed search. Although interest in gastric carcinoids has increased since it was recognized that they are associated with achlorhydria, to date there is no definite evidence that humans taking long-term acid suppressing medication are at increased risk. Type I tumours are associated with autoimmune atrophic gastritis and hypergastrinaemia, type II are associated with Zollinger-Ellison syndrome, multiple endocrine neoplasia-1 and hypergastrinaemia and sporadic type III carcinoids are gastrin-independent and carry the worst prognosis. Careful investigation of these patients is required, particularly to identify the tumour type, the source of hypergastrinaemia and the presence of metastases. Treatment can be directed at the source of hypergastrinaemia if type I or II tumours are still gastrin responsive and not growing autonomously. Type III tumours should be treated surgically. Advances in our understanding of the pathogenesis of gastric carcinoids have led to recent improvements in investigation and management. Challenges remain in identifying the genetic and environmental factors, in addition to hypergastrinaemia, that are responsible for tumour development in susceptible patients.

  6. Radiation binary targeted therapy for HER-2 positive breast cancers: assumptions, theoretical assessment and future directions

    Energy Technology Data Exchange (ETDEWEB)

    Mundy, Daniel W [School of Nuclear Engineering, Purdue University, 400 Central Drive, West Lafayette, IN 47909 (United States); Harb, Wael [Horizon Oncology, The Care Group, Unity Medical Center, Lafayette, IN 47901 (United States); Jevremovic, Tatjana [School of Nuclear Engineering, Purdue University, 400 Central Drive, West Lafayette, IN 47909 (United States)

    2006-03-21

    A novel radiation targeted therapy is investigated for HER-2 positive breast cancers. The proposed concept combines two known approaches, but never used together for the treatment of advanced, relapsed or metastasized HER-2 positive breast cancers. The proposed radiation binary targeted concept is based on the anti HER-2 monoclonal antibodies (MABs) that would be used as vehicles to transport the nontoxic agent to cancer cells. The anti HER-2 MABs have been successful in targeting HER-2 positive breast cancers with high affinity. The proposed concept would utilize a neutral nontoxic boron-10 predicting that anti HER-2 MABs would assure its selective delivery to cancer cells. MABs against HER-2 have been a widely researched strategy in the clinical setting. The most promising antibody is Trastuzumab (Herceptin (registered) ). Targeting HER-2 with the MAB Trastuzumab has been proven to be a successful strategy in inducing tumour regression and improving patient survival. Unfortunately, these tumours become resistant and afflicted women succumb to breast cancer. In the proposed concept, when the tumour region is loaded with boron-10 it is irradiated with neutrons (treatment used for head and neck cancers, melanoma and glioblastoma for over 40 years in Japan and Europe). The irradiation process takes less than an hour producing minimal side effects. This paper summarizes our recent theoretical assessments of radiation binary targeted therapy for HER-2 positive breast cancers on: the effective drug delivery mechanism, the numerical model to evaluate the targeted radiation delivery and the survey study to find the neutron facility in the world that might be capable of producing the radiation effect as needed. A novel method of drug delivery utilizing Trastuzumab is described, followed by the description of a computational Monte Carlo based breast model used to determine radiation dose distributions. The total flux and neutron energy spectra of five currently available

  7. A direct comparison of CellSearch and ISET for circulating tumour-cell detection in patients with metastatic carcinomas

    Science.gov (United States)

    Farace, F; Massard, C; Vimond, N; Drusch, F; Jacques, N; Billiot, F; Laplanche, A; Chauchereau, A; Lacroix, L; Planchard, D; Le Moulec, S; André, F; Fizazi, K; Soria, J C; Vielh, P

    2011-01-01

    Background: Circulating tumour cells (CTCs) can provide information on patient prognosis and treatment efficacy. However, there is no universal method to detect CTC currently available. Here, we compared the performance of two CTC detection systems based on the expression of the EpCAM antigen (CellSearch assay) or on cell size (ISET assay). Methods: Circulating tumour cells were enumerated in 60 patients with metastatic carcinomas of breast, prostate and lung origins using CellSearch according to the manufacturer's protocol and ISET by studying cytomorphology and immunolabelling with anti-cytokeratin or lineage-specific antibodies. Results: Concordant results were obtained in 55% (11 out of 20) of the patients with breast cancer, in 60% (12 out of 20) of the patients with prostate cancer and in only 20% (4 out of 20) of lung cancer patients. Conclusion: Our results highlight important discrepancies between the numbers of CTC enumerated by both techniques. These differences depend mostly on the tumour type. These results suggest that technologies limiting CTC capture to EpCAM-positive cells, may present important limitations, especially in patients with metastatic lung carcinoma. PMID:21829190

  8. The differentiation of malignant and benign human breast tissue at surgical margins and biopsy using x-ray interaction data and Bayesian classification

    International Nuclear Information System (INIS)

    Mersov, A.; Mersov, G.; Al-Ebraheem, A.; Cornacchi, S.; Gohla, G.; Lovrics, P.; Farquharson, M.J.

    2014-01-01

    normal samples (n=35) and tumour samples with ≥50% tumour content (n=16), resulted in 89% of normal tissue samples and, 76% tumour tissue samples being correctly classified. - Highlights: ► Comparing tumour and normal tissue using biometals levels coherent and incoherent scatter profile. ► The use of Bayesian classification to differentiate between malignant and benign breast tissues. ► Classification model has been developed taking the histology of the samples into account. ► The technique has a promise in its ability to identify tumour samples and detect surgical margins

  9. Lidocaine and ropivacaine, but not bupivacaine, demethylate deoxyribonucleic acid in breast cancer cells in vitro

    NARCIS (Netherlands)

    Lirk, P.; Hollmann, M. W.; Fleischer, M.; Weber, N. C.; Fiegl, H.

    2014-01-01

    Lidocaine demethylates deoxyribonucleic acid (DNA) in breast cancer cells. This modification of epigenetic information may be of therapeutic relevance in the perioperative period, because a decrease in methylation can reactivate tumour suppressor genes and inhibit tumour growth. The objectives of

  10. Alterations in Vitamin D signalling and metabolic pathways in breast cancer progression: a study of VDR, CYP27B1 and CYP24A1 expression in benign and malignant breast lesions Vitamin D pathways unbalanced in breast lesions

    International Nuclear Information System (INIS)

    Lopes, Nair; Schmitt, Fernando; Sousa, Bárbara; Martins, Diana; Gomes, Madalena; Vieira, Daniella; Veronese, Luiz A; Milanezi, Fernanda; Paredes, Joana; Costa, José L

    2010-01-01

    Breast cancer is a heterogeneous disease associated with different patient prognosis and responses to therapy. Vitamin D has been emerging as a potential treatment for cancer, as it has been demonstrated that it modulates proliferation, apoptosis, invasion and metastasis, among others. It acts mostly through the Vitamin D receptor (VDR) and the synthesis and degradation of this hormone are regulated by the enzymes CYP27B1 and CYP24A1, respectively. We aimed to study the expression of these three proteins by immunohistochemistry in a series of breast lesions. We have used a cohort comprising normal breast, benign mammary lesions, carcinomas in situ and invasive carcinomas and assessed the expression of the VDR, CYP27B1 and CYP24A1 by immunohistochemistry. The results that we have obtained show that all proteins are expressed in the various breast tissues, although at different amounts. The VDR was frequently expressed in benign lesions (93.5%) and its levels of expression were diminished in invasive tumours (56.2%). Additionally, the VDR was strongly associated with the oestrogen receptor positivity in breast carcinomas. CYP27B1 expression is slightly lower in invasive carcinomas (44.6%) than in benign lesions (55.8%). In contrast, CYP24A1 expression was augmented in carcinomas (56.0% in in situ and 53.7% in invasive carcinomas) when compared with that in benign lesions (19.0%). From this study, we conclude that there is a deregulation of the Vitamin D signalling and metabolic pathways in breast cancer, favouring tumour progression. Thus, during mammary malignant transformation, tumour cells lose their ability to synthesize the active form of Vitamin D and respond to VDR-mediated Vitamin D effects, while increasing their ability to degrade this hormone

  11. Patterns of Immune Infiltration in Breast Cancer and Their Clinical Implications: A Gene-Expression-Based Retrospective Study

    Science.gov (United States)

    Ali, H. Raza; Chlon, Leon; Pharoah, Paul D. P.; Caldas, Carlos

    2016-01-01

    survival patterns by ER status and associations with patient age at diagnosis. The main limitations of this study are the use of diverse platforms for measuring gene expression, including some not previously used with CIBERSORT, and the combined analysis of different forms of follow-up across studies. Conclusions Large differences in the cellular composition of the immune infiltrate in breast tumours appear to exist, and these differences are likely to be important determinants of both prognosis and response to treatment. In particular, macrophages emerge as a possible target for novel therapies. Detailed analysis of the cellular immune response in tumours has the potential to enhance clinical prediction and to identify candidates for immunotherapy. PMID:27959923

  12. [Neonatal tumours and congenital malformations].

    Science.gov (United States)

    Berbel Tornero, O; Ortega García, J A; Ferrís i Tortajada, J; García Castell, J; Donat i Colomer, J; Soldin, O P; Fuster Soler, J L

    2008-06-01

    The association between pediatric cancer and congenital abnormalities is well known but, there is no exclusive data on the neonatal period and the underlying etiopathogenic mechanisms are unknown. First, to analyze the frequency of neonatal tumours associated with congenital abnormalities; and second, to comment on the likely etiopathogenic hypotheses of a relationship between neonatal tumours and congenital abnormalities. Historical series of neonatal tumours from La Fe University Children's Hospital in Valencia (Spain), from January 1990 to December 1999. Histological varieties of neonatal tumours and associated congenital abnormalities were described. A systematic review of the last 25 years was carried out using Medline, Cancerlit, Index Citation Science and Embase. The search profile used was the combination of "neonatal/congenital-tumors/cancer/neoplasms" and "congenital malformations/birth defects". 72 neonatal tumours were identified (2.8% of all pediatric cancers diagnosed in our hospital) and in 15 cases (20.8%) there was some associated malformation, disease or syndrome. The association between congenital abnormalities and neonatal tumours were: a) angiomas in three patients: two patients with congenital heart disease with a choanal stenosis, laryngomalacia; b) neuroblastomas in two patients: horseshoe kidney with vertebral anomalies and other with congenital heart disease; c) teratomas in two patients: one with cleft palate with vertebral anomalies and other with metatarsal varus; d) one tumour of the central nervous system with Bochdaleck hernia; e) heart tumours in four patients with tuberous sclerosis; f) acute leukaemia in one patient with Down syndrome and congenital heart disease; g) kidney tumour in one case with triventricular hydrocephaly, and h) adrenocortical tumour: hemihypertrophy. The publications included the tumours diagnosed in different pediatric periods and without unified criteria to classify the congenital abnormalities. Little data

  13. Metastatic tumours to the thyroid gland: report of 3 cases and brief review of the literature

    International Nuclear Information System (INIS)

    Vardar, Enver; Erkan, Nazif; Bayol, Umit; Yılmaz, Cengiz; Dogan, Murat

    2010-01-01

    Metastases to the thyroid are encountered rarely in clinical practice, but the number of cases seems to have increased in recent years. The reason of this increase may be a more frequent use of fine-needle aspiration biopsy (FNAB) and the use of more sophisticated, complicated imaging techniques in patients with thyroid masses. Also, in addition to these reasons, the use of more organo-specific immunohistochemical antibodies in the examination of surgical specimens may affect the differential diagnosis of malignant tumours. Three metastatic tumours to thyroid were found in the retrospective review of malignant thyroid tumours diagnosed between January 1993 and December 2007. The primary tumours were clear cell carcinoma of the kidney, squamous cell carcinoma of the lung and breast carcinoma-ductal type. A detailed clinical history, careful histological examination and essential immunohistochemistry helped in attaining the correct diagnosis

  14. Shear wave elastography of breast cancer: Sensitivity according to histological type in a large cohort.

    Science.gov (United States)

    Evans, Andrew; Sim, Yee Ting; Thomson, Kim; Jordan, Lee; Purdie, Colin; Vinnicombe, Sarah J

    2016-04-01

    To define the shear wave elastography (SWE) characteristics of breast cancer histological types by size in a large cohort. Consecutive patients with US visible masses underwent SWE. All those with confirmed invasive breast cancer were included in the study. Histologic type was ascertained from core biopsy and surgical resection specimens. For each type, mean and median values for Emean and Emax were ascertained. Commoner tumour types were further analysed by invasive size. The significance of differences was established using the Chi-square test. 1137 tumours constituted the study group. The proportion of tumours with Emean below 50 kPa was higher in tubular cancers (23%) compared to ductal carcinomas of no specific type (DNST) (6%) (p breast cancer histological types have similar SWE characteristics. The exception is tubular cancer which has significantly lower stiffness than other histologic types, accounted for largely by their small size. Copyright © 2016 Elsevier Ltd. All rights reserved.

  15. Arterial spin labelling perfusion MRI of breast cancer using FAIR TrueFISP: Initial results

    International Nuclear Information System (INIS)

    Buchbender, S.; Obenauer, S.; Mohrmann, S.; Martirosian, P.; Buchbender, C.; Miese, F.R.; Wittsack, H.J.; Miekley, M.; Antoch, G.; Lanzman, R.S.

    2013-01-01

    Aim: To assess the feasibility of an unenhanced, flow-sensitive, alternating inversion recovery-balanced steady-state free precession (FAIR TrueFISP) arterial spin labelling (ASL) magnetic resonance imaging (MRI) technique for quantification of breast cancer perfusion. Materials and methods: Eighteen untreated breast tumour patients (mean age 53 ± 17 years, range 30–68 years) and four healthy controls (mean age 51 ± 14 years, range 33–68 years) were enrolled in this study and were imaged using a clinical 1.5 T MRI machine. Perfusion measurements were performed using a coronal single-section ASL FAIR TrueFISP technique in addition to a routine breast MRI examination. T1 relaxation time of normal breast parenchyma was determined in four healthy volunteers using the variable flip angle approach. The definitive diagnosis was obtained at histology after biopsy or surgery and was available for all patients. Results: ASL perfusion was successfully acquired in 13 of 18 tumour patients and in all healthy controls. The mean ASL perfusion of invasive ductal carcinoma tissue was significantly higher (88.2 ± 39.5 ml/100 g/min) compared to ASL perfusion of normal breast parenchyma (24.9 ± 12.7 ml/100 g/min; p < 0.05) and invasive lobular carcinoma (30.5 ± 4.3 ml/100 g/min; p < 0.05). No significant difference was found between the mean ASL perfusion of normal breast parenchyma and invasive lobular carcinoma tissue (p = 0.97). Conclusion: ASL MRI enables quantification of breast cancer perfusion without the use of contrast material. However, its impact on diagnosis and therapy management of breast tumours has to be evaluated in larger patient studies

  16. Combined use of 18F-FDG PET/CT and MRI for response monitoring of breast cancer during neoadjuvant chemotherapy

    International Nuclear Information System (INIS)

    Pengel, Kenneth E.; Loo, Claudette E.; Koolen, Bas B.; Vogel, Wouter V.; Valdes Olmos, Renato A.; Wesseling, Jelle; Lips, Esther H.; Rutgers, Emiel J.T.; Vrancken Peeters, Marie Jeanne T.F.D.; Rodenhuis, Sjoerd; Gilhuijs, Kenneth G.A.

    2014-01-01

    To explore the potential complementary value of PET/CT and dynamic contrast-enhanced MRI in predicting pathological response to neoadjuvant chemotherapy (NAC) of breast cancer and the dependency on breast cancer subtype. We performed 18 F-FDG PET/CT and MRI examinations before and during NAC. The imaging features evaluated on both examinations included baseline and changes in 18 F-FDG maximum standardized uptake value (SUVmax) on PET/CT, and tumour morphology and contrast uptake kinetics on MRI. The outcome measure was a (near) pathological complete response ((near-)pCR) after surgery. Receiver operating characteristic curves with area under the curve (AUC) were used to evaluate the relationships between patient, tumour and imaging characteristics and tumour responses. Of 93 patients, 43 achieved a (near-)pCR. The responses varied among the different breast cancer subtypes. On univariate analysis the following variables were significantly associated with (near-)pCR: age (p = 0.033), breast cancer subtype (p < 0.001), relative change in SUVmax on PET/CT (p < 0.001) and relative change in largest tumour diameter on MRI (p < 0.001). The AUC for the relative reduction in SUVmax on PET/CT was 0.78 (95 % CI 0.68-0.88), and for the relative reduction in tumour diameter at late enhancement on MRI was 0.79 (95 % CI 0.70-0.89). The AUC increased to 0.90 (95 % CI 0.83-0.96) in the final multivariate model with PET/CT, MRI and breast cancer subtype combined (p = 0.012). PET/CT and MRI showed comparable value for monitoring response during NAC. Combined use of PET/CT and MRI had complementary potential. Research with more patients is required to further elucidate the dependency on breast cancer subtype. (orig.)

  17. ATM down-regulation is associated with poor prognosis in sporadic breast carcinomas

    DEFF Research Database (Denmark)

    Bueno, R C; Canevari, R A; Villacis, R A R

    2014-01-01

    BACKGROUND: Ataxia telangiectasia-mutated (ATM) gene downexpression has been reported in sporadic breast carcinomas (BC); however, the prognostic value and mechanisms of ATM deregulation remain unclear. PATIENTS AND METHODS: ATM and miRNAs (miR-26a, miR-26b, miR-203, miR-421, miR-664, miR-576-5p...... and miR-18a) expression levels were evaluated by quantitative real-time PCR (RT-qPCR) in 52 BC and 3 normal breast samples. ATM protein expression was assessed by immunohistochemistry in 968 BC and 35 adjacent normal breast tissues. ATM copy number alteration was detected by array comparative genomic...... hybridization (aCGH) in 42 tumours. RESULTS: Low ATM levels were associated with tumour grade. Absence of ATM protein expression was associated with distant metastasis (P ATM...

  18. Incidence of heart disease in 35,000 women treated with radiotherapy for breast cancer in Denmark and Sweden

    International Nuclear Information System (INIS)

    McGale, Paul; Darby, Sarah C.; Hall, Per; Adolfsson, Jan; Bengtsson, Nils-Olof; Bennet, Anna M.; Fornander, Tommy; Gigante, Bruna; Jensen, Maj-Britt; Peto, Richard; Rahimi, Kazem; Taylor, Carolyn W.; Ewertz, Marianne

    2011-01-01

    Purpose: To study incidence of radiation-related heart disease in a large population of breast cancer patients followed for up to 30 years. Material and methods: 72,134 women diagnosed with breast cancer in Denmark or Sweden during 1976-2006 and followed prospectively. Radiation-related risk was studied by comparing women with left-sided and right-sided tumours. Results: 34,825 women (48%) received radiotherapy. Among unirradiated women tumour laterality had little relevance to heart disease. Among irradiated women mean dose to the whole heart was 6.3 Gy for left-sided tumours and 2.7 Gy for right-sided tumours. Mortality was similar in irradiated women with left-sided and right-sided tumours, but incidence ratios, left-sided versus right-sided, were raised: acute myocardial infarction 1.22 (95% CI 1.06-1.42), angina 1.25 (1.05-1.49), pericarditis 1.61 (1.06-2.43), valvular heart disease 1.54 (1.11-2.13). Incidence ratios for all heart disease were as high for women irradiated since 1990 (1.09 [1.00-1.19]) as for women irradiated during 1976-1989 (1.08 [0.99-1.17]), and were higher for women diagnosed with ischaemic heart disease prior to breast cancer than for other women (1.58 [1.19-2.10] versus 1.08 [1.01-1.15], p for difference = 0.01). Conclusions: Breast cancer radiotherapy has, at least until recently, increased the risk of developing ischaemic heart disease, pericarditis and valvular disease. Women with ischaemic heart disease before breast cancer diagnosis may have incurred higher risks than others.

  19. Immunoradiometric assay of a novel proliferation marker: tumour polypeptide specific antigen in breast cancer management in north India

    International Nuclear Information System (INIS)

    Phanna-Hazra, P.; Sharma, U.; Gupta, K.K.; Bhatnagar, V.; Idnani, R.; Gangwar, P.K.; Hazra, D.K.

    2004-01-01

    Tissue Polypeptide Specific Antigen (TPS) is a novel tumour marker defined by the monoclonal antibody M3 ,discovered by Bjorklund,which is claimed to be a proliferation marker, and belonging to the cytokeratin 8-18 family. M3 defines this antigen in particular out of a group of Tissue Polypeptide antigens (TPA) charecterised by the same Swedish group and was claimed to be a pancarcinoma antigen reportedly being elevated in several different cancers in the European literature.Pancarcinoma markers are of interest in relation to cancer detection as well as for assessing therapy and prognosis.Pancarcinoma antigens are also of interest for radiobioconjugate immunotargetting both for diagnosis as well as for therapy. There were no reports on this marker in an Indian population and therefore this study was initiated at two institutions in Meerut and Agra, both in the northern state of Uttar Pradesh. In addition to 250 healthy controls, 288 cases of breast cancer were studied .In addituion benign disorders were studied: breast fibroadenosis 16, breast fibro adenoma 5, breast abscess 4. TPS levels were determined by an immunoradiometric assay. In controls all but 4 had values less than 80 Units/1,the upper normal level quoted by Bjorklund.The relationship of the serum levels of the markers to histological grade and anatomical stage of the tumour were studied. In addition several of the cases underwent therapy with chemotherapy /radiotherapy/surgery or combinations thereof. The response to treatment during follow up was categorized as Complete emission(CR),Partial Remission (PR)Stable Disease(SD), Progressive Disease(PD)and recurrence (R) by the respective clinicians using standard criteria. In the cancer subjects there was a close correlation of TPS elevation with anatomical stage. 10 cases belonged to stage 1 with TPS levels 176.1+-103.94 Units/L ,61 to stage II(TPS levels 206.45 +-168.23).,79 to stage Ilia (TPS 251.5+-168.53),83 to stage IIIB (TPS 537.35+- 691.71),and 55

  20. Generation of IgE-based immunotherapies against HER-2 overexpressing tumours

    International Nuclear Information System (INIS)

    Knittelfelder, R.

    2010-01-01

    In combination with chemotherapy or radiation, passive immunotherapy with monoclonal antibodies is state of the art in cancer therapy. For this purpose, two properties of antibodies are harnessed: i) via the Fab fragment they bind a specific tumour antigen and ii) via the Fc portion they recruit effector cells and activate the complement system. One of these antibodies is trastuzumab (Herceptin), a growth-inhibitory humanized monoclonal IgG1 antibody recognizing the tumour antigen HER-2, which is overexpressed in 30% of human breast cancers. Interestingly, all antibodies applied for passive immunotherapy are so far exclusively of the IgG subclass. In contrast, antibodies of the IgE subclass are best-known for their detrimental function in type I hypersensitivity. It is little-known that IgE has anti-tumour capacity which could be exploited for immunotherapy of cancer. Thus, the aim of this doctoral thesis was to examine alternative strategies for cancer treatment based on IgE antibodies, and to compare their efficacy with that of IgG. The oral immunization route is well suited for the induction of a Th2 immunity including high affine IgE responses to administered antigens. Therefore, the establishment of an IgE dependent food allergy model in mice is described, which we applied also for our cancer studies. When mice were fed with different concentrations of ovalbumin under concomitant anti-acid medication, an antigen-specific IgE induction in a Th2 environment could be achieved. This oral vaccination regimen was also used for feeding HER-2 mimotopes, i.e. epitope-mimics of the anti-HER-2 IgG antibody trastuzumab. Indeed, these mimotopes induced IgE antibodies recognizing the tumour antigen which were able to bind HER-2 overexpressing breast cancer cells and led to tumour cell lysis. Complementary to this active immunotherapeutic approach a trastuzumab-like IgE antibody for passive immunotherapy was constructed. We could show that this trastuzumab IgE exhibited the

  1. Gene transfer preferentially selects MHC class I positive tumour cells and enhances tumour immunogenicity.

    Science.gov (United States)

    Hacker, Ulrich T; Schildhauer, Ines; Barroso, Margarita Céspedes; Kofler, David M; Gerner, Franz M; Mysliwietz, Josef; Buening, Hildegard; Hallek, Michael; King, Susan B S

    2006-05-01

    The modulated expression of MHC class I on tumour tissue is well documented. Although the effect of MHC class I expression on the tumorigenicity and immunogenicity of MHC class I negative tumour cell lines has been rigorously studied, less is known about the validity of gene transfer and selection in cell lines with a mixed MHC class I phenotype. To address this issue we identified a C26 cell subline that consists of distinct populations of MHC class I (H-2D/K) positive and negative cells. Transient transfection experiments using liposome-based transfer showed a lower transgene expression in MHC class I negative cells. In addition, MHC class I negative cells were more sensitive to antibiotic selection. This led to the generation of fully MHC class I positive cell lines. In contrast to C26 cells, all transfectants were rejected in vivo and induced protection against the parental tumour cells in rechallenge experiments. Tumour cell specificity of the immune response was demonstrated in in vitro cytokine secretion and cytotoxicity assays. Transfectants expressing CD40 ligand and hygromycin phosphotransferase were not more immunogenic than cells expressing hygromycin resistance alone. We suggest that the MHC class I positive phenotype of the C26 transfectants had a bearing on their immunogenicity, because selected MHC class I positive cells were more immunogenic than parental C26 cells and could induce specific anti-tumour immune responses. These data demonstrate that the generation of tumour cell transfectants can lead to the selection of subpopulations that show an altered phenotype compared to the parental cell line and display altered immunogenicity independent of selection marker genes or other immune modulatory genes. Our results show the importance of monitoring gene transfer in the whole tumour cell population, especially for the evaluation of in vivo therapies targeted to heterogeneous tumour cell populations.

  2. Early dissemination seeds metastasis in breast cancer

    Science.gov (United States)

    Hosseini, Hedayatollah; Obradović, Milan M.S.; Hoffmann, Martin; Harper, Kathryn; Sosa, Maria Soledad; Werner-Klein, Melanie; Nanduri, Lahiri Kanth; Werno, Christian; Ehrl, Carolin; Maneck, Matthias; Patwary, Nina; Haunschild, Gundula; Gužvić, Miodrag; Reimelt, Christian; Grauvogl, Michael; Eichner, Norbert; Weber, Florian; Hartkopf, Andreas; Taran, Florin-Andrei; Brucker, Sara Y.; Fehm, Tanja; Rack, Brigitte; Buchholz, Stefan; Spang, Rainer; Meister, Gunter; Aguirre-Ghiso, Julio A.; Klein, Christoph A.

    2016-01-01

    Accumulating data suggest that metastatic dissemination often occurs early during tumour formation but the mechanisms of early metastatic spread have not yet been addressed. Here, we studied metastasis in a HER2-driven mouse breast cancer model and found that progesterone-induced signalling triggered migration of cancer cells from early lesions shortly after HER2 activation, but promoted proliferation in advanced primary tumour cells. The switch from migration to proliferation was regulated by elevated HER2 expression and increased tumour cell density involving miRNA-mediated progesterone receptor (PGR) down-regulation and was reversible. Cells from early, low-density lesions displayed more stemness features than cells from dense, advanced tumours, migrated more and founded more metastases. Strikingly, we found that at least 80% of metastases were derived from early disseminated cancer cells (DCC). Karyotypic and phenotypic analysis of human disseminated cancer cells and primary tumours corroborated the relevance of these findings for human metastatic dissemination. PMID:27974799

  3. Homotypic Cell Cannibalism and Cannibalism Index-A Four Year Study in Inltrating Ductal Carcinoma Breast

    Directory of Open Access Journals (Sweden)

    Alok Mohan

    2016-01-01

    Full Text Available Background: Homotypic cell cannibalism is a hallmark of malignant lesions. It serves as an emerging indicator of both the anaplastic grade and invasiveness. Aim and Objectives: The present study was conducted to correlate tumour cytological grade with the incidences of cell cannibalism. Material and Methods: Three stained smears per case were submitted for cytological grading. The smears were then submitted for visually counting the number of examples of cell cannibalism and the cannibalism index was calculated. Results: Seventy cytological diagnosed cases of breast malignancies were assessed for the presence of cell cannibalism. The results were correlated with the cytological grade of carcinoma. The study revealed that cell cannibalism was encountered in 68.57% cases of breast carcinoma. 44.4% of grade I, 71.4% of grade II and 100% of grade III tumours grade. It was observed that grade I tumours had mean cannibalism per smear of 1.62/1000 tumour cells smear, grade II mean cannibalism per smear of 2.50/ 1000 tumour cells and grade III mean cannibalism per smear 4.90/1000 tumour cells. Tumour diathesis and metastasis were also found more in cannibalism positive cases. Conclusion: The phenomenon of cell cannibalism was encountered more in high grade tumours. Thus it can be designated as an emerging marker of anaplasia and aggressive tumour behaviour

  4. EpCAM as multi-tumour target for near-infrared fluorescence guided surgery

    International Nuclear Information System (INIS)

    Driel, P. B. A. A. van; Boonstra, M. C.; Prevoo, H. A. J. M.; Giessen, M. van de; Snoeks, T. J. A.; Tummers, Q. R. J. G.; Keereweer, S.; Cordfunke, R. A.; Fish, A.; Eendenburg, J. D. H. van; Lelieveldt, B. P. F.; Dijkstra, J.; Velde, C. J. H. van de; Kuppen, P. J. K.; Vahrmeijer, A. L.; Löwik, C. W. G. M.; Sier, C. F. M.

    2016-01-01

    Evaluation of resection margins during cancer surgery can be challenging, often resulting in incomplete tumour removal. Fluorescence-guided surgery (FGS) aims to aid the surgeon to visualize tumours and resection margins during surgery. FGS relies on a clinically applicable imaging system in combination with a specific tumour-targeting contrast agent. In this study EpCAM (epithelial cell adhesion molecule) is evaluated as target for FGS in combination with the novel Artemis imaging system. The NIR fluorophore IRDye800CW was conjugated to the well-established EpCAM specific monoclonal antibody 323/A3 and an isotype IgG1 as control. The anti-EpCAM/800CW conjugate was stable in serum and showed preserved binding capacity as evaluated on EpCAM positive and negative cell lines, using flow cytometry and cell-based plate assays. Four clinically relevant orthotopic tumour models, i.e. colorectal cancer, breast cancer, head and neck cancer, and peritonitis carcinomatosa, were used to evaluate the performance of the anti-EpCAM agent with the clinically validated Artemis imaging system. The Pearl Impulse small animal imaging system was used as reference. The specificity of the NIRF signal was confirmed using bioluminescence imaging and green-fluorescent protein. All tumour types could clearly be delineated and resected 72 h after injection of the imaging agent. Using NIRF imaging millimetre sized tumour nodules were detected that were invisible for the naked eye. Fluorescence microscopy demonstrated the distribution and tumour specificity of the anti-EpCAM agent. This study shows the potential of an EpCAM specific NIR-fluorescent agent in combination with a clinically validated intraoperative imaging system to visualize various tumours during surgery

  5. Evaluating genome-wide association study-identified breast cancer risk variants in African-American women.

    Directory of Open Access Journals (Sweden)

    Jirong Long

    Full Text Available Genome-wide association studies (GWAS, conducted mostly in European or Asian descendants, have identified approximately 67 genetic susceptibility loci for breast cancer. Given the large differences in genetic architecture between the African-ancestry genome and genomes of Asians and Europeans, it is important to investigate these loci in African-ancestry populations. We evaluated index SNPs in all 67 breast cancer susceptibility loci identified to date in our study including up to 3,300 African-American women (1,231 cases and 2,069 controls, recruited in the Southern Community Cohort Study (SCCS and the Nashville Breast Health Study (NBHS. Seven SNPs were statistically significant (P ≤ 0.05 with the risk of overall breast cancer in the same direction as previously reported: rs10069690 (5p15/TERT, rs999737 (14q24/RAD51L1, rs13387042 (2q35/TNP1, rs1219648 (10q26/FGFR2, rs8170 (19p13/BABAM1, rs17817449 (16q12/FTO, and rs13329835 (16q23/DYL2. A marginally significant association (P<0.10 was found for three additional SNPs: rs1045485 (2q33/CASP8, rs4849887 (2q14/INHBB, and rs4808801 (19p13/ELL. Three additional SNPs, including rs1011970 (9p21/CDKN2A/2B, rs941764 (14q32/CCDC88C, and rs17529111 (6q14/FAM46A, showed a significant association in analyses conducted by breast cancer subtype. The risk of breast cancer was elevated with an increasing number of risk variants, as measured by quintile of the genetic risk score, from 1.00 (reference, to 1.75 (1.30-2.37, 1.56 (1.15-2.11, 2.02 (1.50-2.74 and 2.63 (1.96-3.52, respectively, (P = 7.8 × 10(-10. Results from this study highlight the need for large genetic studies in AAs to identify risk variants impacting this population.

  6. Menarche menopause breast cancer risk individual

    NARCIS (Netherlands)

    Collaborative Group on Hormonal Factors in Breast Cancer; Bausch-Goldbohm, R.A.

    2012-01-01

    BACKGROUND:Menarche and menopause mark the onset and cessation, respectively, of ovarian activity associated with reproduction, and affect breast cancer risk. Our aim was to assess the strengths of their effects and determine whether they depend on characteristics of the tumours or the affected

  7. Admixture mapping of African-American women in the AMBER Consortium identifies new loci for breast cancer and estrogen-receptor subtypes

    Directory of Open Access Journals (Sweden)

    Edward Antonio Ruiz-Narvaez

    2016-09-01

    Full Text Available Recent genetic admixture coupled with striking differences in incidence of estrogen receptor (ER breast cancer subtypes, as well as severity, between women of African and European ancestry, provides an excellent rationale for performing admixture mapping in African American women with breast cancer risk. We performed the largest breast cancer admixture mapping study with in African American women to identify novel genomic regions associated with the disease. We conducted a genome-wide admixture scan using 2,624 autosomal ancestry informative markers (AIMs in 3,629 breast cancer cases (including 1,968 ER-positive, 1093 ER-negative and 601 triple-negative and 4,658 controls from the African American Breast Cancer Epidemiology and Risk (AMBER Consortium, a collaborative study of four large geographically different epidemiological studies of breast cancer in African American women. We used an independent case-control study to test for SNP association in regions with genome-wide significant admixture signals. We found two novel genome-wide significant regions of excess African ancestry, 4p16.1 and 17q25.1, associated with ER-positive breast cancer. Two regions known to harbor breast cancer variants, 10q26 and 11q13, were also identified with excess of African ancestry. Fine-mapping of the identified genome-wide significant regions suggests the presence of significant genetic associations with ER-positive breast cancer in 4p16.1 and 11q13. In summary, we identified three novel genomic regions associated with breast cancer risk by ER status, suggesting that additional previously unidentified variants may contribute to the racial differences in breast cancer risk in the African American population.

  8. The immunomodulator PSK induces in vitro cytotoxic activity in tumour cell lines via arrest of cell cycle and induction of apoptosis

    International Nuclear Information System (INIS)

    Jiménez-Medina, Eva; Berruguilla, Enrique; Romero, Irene; Algarra, Ignacio; Collado, Antonia; Garrido, Federico; Garcia-Lora, Angel

    2008-01-01

    Protein-bound polysaccharide (PSK) is derived from the CM-101 strain of the fungus Coriolus versicolor and has shown anticancer activity in vitro and in in vivo experimental models and human cancers. Several randomized clinical trials have demonstrated that PSK has great potential in adjuvant cancer therapy, with positive results in the adjuvant treatment of gastric, esophageal, colorectal, breast and lung cancers. These studies have suggested the efficacy of PSK as an immunomodulator of biological responses. The precise molecular mechanisms responsible for its biological activity have yet to be fully elucidated. The in vitro cytotoxic anti-tumour activity of PSK has been evaluated in various tumour cell lines derived from leukaemias, melanomas, fibrosarcomas and cervix, lung, pancreas and gastric cancers. Tumour cell proliferation in vitro was measured by BrdU incorporation and viable cell count. Effect of PSK on human peripheral blood lymphocyte (PBL) proliferation in vitro was also analyzed. Studies of cell cycle and apoptosis were performed in PSK-treated cells. PSK showed in vitro inhibition of tumour cell proliferation as measured by BrdU incorporation and viable cell count. The inhibition ranged from 22 to 84%. Inhibition mechanisms were identified as cell cycle arrest, with cell accumulation in G 0 /G 1 phase and increase in apoptosis and caspase-3 expression. These results indicate that PSK has a direct cytotoxic activity in vitro, inhibiting tumour cell proliferation. In contrast, PSK shows a synergistic effect with IL-2 that increases PBL proliferation. These results indicate that PSK has cytotoxic activity in vitro on tumour cell lines. This new cytotoxic activity of PSK on tumour cells is independent of its previously described immunomodulatory activity on NK cells

  9. Brachytherapy for breast cancer

    International Nuclear Information System (INIS)

    Spikalovas, V.; Mudenas, A.; Karoesiene, E.; Mickevicius, R.

    1996-01-01

    In 1987-1995 a total of 347 patients with breast cancer underwent interstitial treatment. Two methods of irradiation were applied. 1. When patients refused surgery, external radiotherapy was given followed by implant radiotherapy for a dose of 20-30 Gy. Needle sources were applied for treatment with an increasing activity on the ends. The application of special template devices made it possible to implant radioactive sources in a strictly pre-set geometry. This allowed to place the sources in the necessary geometry for the whole course of irradiation. Dosimetric planning was performed in Gray-equivalents to a selected isodose curve mostly 85%. Treatment time was 20-50 hours. 2. In cases when the tumour was localized in the medial quadrant of breast, interstitial therapy was applied to the parasternal lymph nodes. During mastectomy catheters were placed in a. thoracica interna of the corresponding side. On the first or second postoperative day flexible radioactive sources were inserted into catheters. Their active length was 10-12 cm. Irradiation dose at a distance of 2 cm from the centre of source was 40-45 Gy. Results: There was minimum radiation effect on the adjusting organs and tissues. Local recurrence of tumour in the region of irradiation was in 6 patients. Conclusions: The application of interstitial radiotherapy in treatment of breast cancer is effective and the results of radiation treatment are encouraging

  10. [Radiologic follow-up after breast-conserving surgery: value of MRI examination of the breast].

    Science.gov (United States)

    Polgár, C; Forrai, G; Szabó, E; Riedl, E; Fodor, J; Fornet, B; Németh, G

    1999-11-21

    The aim of the study was to establish an objective method for evaluation the extent, topography and quantity of skin and soft tissue side effects after tele- and/or brachyradiotherapy of the conserved breast and to compare the sequales of different radiation methods. 26 patients operated on for T1-2 N0-1 breast cancer underwent the following kinds of postoperative radiotherapy: 1. 46-50 Gy whole breast teletherapy + 10-16 Gy electron boost (5 patients), 2. 46-50 Gy teletherapy + 10-15 Gy HDR brachytherapy boost (12 patients), 3. 46-50 Gy teletherapy (6 patients), 4. 36,4 Gy sole HDR brachytherapy of the tumour bed (5 patients). The postirradiation side effects were examined by MRI, mammogram, US and physical examination, as well. MRI was performed on a 0.5 T, double breast coil, with SE-T1, SE-T2 and 3D-GE sequences. The findings of MRI and mammography were compared to physically detectable side effects using the RTOG/EORTC late radiation morbidity scoring scheme. US is useful in the measurement of skin thickening and in the diagnosis of fat necrosis. Mammography and physical examination are very subjective and low specificity methods to evaluate postirradiation side effects. MRI is a suitable and more objective method to detect the real extent and quantity of skin thickening and fibrosis. The incidence of > or = G2 side effects of skin and breast parenchyma were 64.5 and 32.2%, respectively. The differences between the side effects of whole breast irradiation and sole brachytherapy of the tumour bed are also clearly demonstrated. Brachytherapy alone is feasible without compromising cosmetic results. The authors established the MRI criteria for categorization the extent and grade of skin thickening and fibrosis (focal vs diffuse, grade 1-4). Breast MRI is an objective tool for assisting to the evaluation of the side effects of postoperative radiotherapy.

  11. Diagnostic and prognostic relevance of Cullin1 expression in invasive ductal carcinoma of the breast.

    Science.gov (United States)

    Min, Kyueng-Whan; Kim, Dong-Hoon; Do, Sung-Im; Sohn, Jin Hee; Chae, Seoung Wan; Pyo, Jung-Soo; Park, Chan Heun; Oh, Young-Ha; Jang, Ki-Seok; Kim, Hack-Lyoung; Kim, Min

    2012-10-01

    Cullin1 (Cul1) is a matrix degrading enzyme known to be involved in the remodelling of extracellular matrix proteins. This enzyme has recently been reported to play a key role in tumour progression and its presence is associated with poor clinical outcome for several different types of tumours. 159 patients diagnosed with invasive ductal carcinoma between 2000 and 2005 were studied. Cul1 expression was analysed by immunohistochemical staining on a tissue microarray. The relationship between Cul1 expression and clinicopathological parameters was evaluated. Tumour expression of Cul1 was correlated with prognostic factors such as high histological grade and p53 expression, and was also linked to negative ER and positive HER2 as therapeutic markers (all pCul1 expression in both univariate and multivariate analyses (all pCul1 expression was significantly associated with high-grade tumours and poor prognosis, suggesting that it may play a role in breast tumour progression. Cul1 expression may therefore be crucial for the prediction of disease outcome in breast cancer patients.

  12. Linkage disequilibrium pattern of the ATM gene in breast cancer patients and controls; association of SNPs and haplotypes to radio-sensitivity and post-lumpectomy local recurrence

    International Nuclear Information System (INIS)

    Edvardsen, Hege; Tefre, Toril; Jansen, Laila; Vu, Phuong; Haffty, Bruce G; Fosså, Sophie D; Kristensen, Vessela N; Børresen-Dale, Anne-Lise

    2007-01-01

    The ATM protein is activated as a result of ionizing radiation, and genetic variants of the ATM gene may therefore affect the level of radiation-induced damage. Individuals heterozygous for ATM mutations have been reported to have an increased risk of malignancy, especially breast cancer. Norwegian breast cancer patients (272) treated with radiation (252 of which were evaluated for radiation-induced adverse side effects), 95 Norwegian women with no known history of cancer and 95 American breast cancer patients treated with radiation (44 of which developed ipsilateral breast tumour recurrence, IBTR) were screened for sequence variations in all exons of the ATM gene as well as known intronic variants by denaturating high performance liquid chromatography (dHPLC) followed by sequencing to determine the nature of the variant. A total of 56 variants were identified in the three materials combined. A borderline significant association with breast cancer risk was found for the 1229 T>C (Val>Ala) substitution in exon 11 (P-value 0.055) between the Norwegian controls and breast cancer patients as well as a borderline significant difference in haplotype distribution (P-value 0.06). Adverse side effects, such as: development of costal fractures and telangiectasias, subcutaneous and lung fibrosis, pleural thickening and atrophy were evaluated in the Norwegian patients. Significant associations were found for several of the identified variants such as rs1800058 (Leu > Phe) where a decrease in minor allele frequency was found with increasing level of adverse side effects for the clinical end-points pleural thickening and lung fibrosis, thus giving a protective effect. Overall our results indicate a role for variation in the ATM gene both for risk of developing breast cancer, and in radiation induced adverse side effects. No association could be found between risk of developing ipsilateral breast tumour recurrence and any of the sequence variants found in the American patient

  13. Predictors of axillary lymph node metastases in women with early breast cancer in Singapore.

    Science.gov (United States)

    Tan, L G L; Tan, Y Y; Heng, D; Chan, M Y

    2005-12-01

    The presence of axillary lymph node metastases is an important prognostic factor in breast cancer. Sentinel lymph node biopsy (SLNB) is an emerging method for the staging of the axilla. It is hoped that with SLNB, the morbidity from axillary lymph node dissection (ALND) can be avoided without compromising the staging and management of early breast cancer. However, only patients found to be SLNB negative benefit from this procedure, as those with positive SLNB may still require ALND. Our objective is to study the various clinico-pathological factors to find predictive factors for axillary lymph node involvement in early breast cancer. It is hoped that with these factors, we will be better able to identify groups of patients most likely to benefit from SLNB. A retrospective study of 380 early breast cancer cases (stage T1 and T2, N0, N1, M0) in women treated in the Department of General Surgery, Tan Tock Seng Hospital, between January 1999 and August 2002, was conducted. Incidence of nodal metastases was correlated with clinico-pathological factors, and analysed by univariate and multivariate analyses. Approximately 35 percent of the 380 cases of early breast cancer had nodal metastases. Multivariate analyses revealed four independent predictors of node positivity: tumour size (p-value equals 0.0001), presence of lymphovascular invasion (p-value is less than 0.0001), tumours with histology other than invasive ductal or lobular carcinoma (p-value equals 0.04), and presence of progesterone receptors (p-value equals 0.05). We have found independent preoperative predictive factors in our local population for the presence of nodal metastases. This information can aid patient selection for SLNB and improve patient counselling.

  14. Effects of biosurfactants on the viability and proliferation of human breast cancer cells.

    Science.gov (United States)

    Duarte, Cristina; Gudiña, Eduardo J; Lima, Cristovao F; Rodrigues, Ligia R

    2014-01-01

    Biosurfactants are molecules with surface activity produced by microorganisms that can be used in many biomedical applications. The anti-tumour potential of these molecules is being studied, although results are still scarce and few data are available regarding the mechanisms underlying such activity. In this work, the anti-tumour activity of a surfactin produced by Bacillus subtilis 573 and a glycoprotein (BioEG) produced by Lactobacillus paracasei subsp. paracasei A20 was evaluated. Both biosurfactants were tested against two breast cancer cell lines, T47D and MDA-MB-231, and a non-tumour fibroblast cell line (MC-3 T3-E1), specifically regarding cell viability and proliferation. Surfactin was found to decrease viability of both breast cancer cell lines studied. A 24 h exposure to 0.05 g l(-1) surfactin led to inhibition of cell proliferation as shown by cell cycle arrest at G1 phase. Similarly, exposure of cells to 0.15 g l(-1) BioEG for 48 h decreased cancer cells' viability, without affecting normal fibroblasts. Moreover, BioEG induced the cell cycle arrest at G1 for both breast cancer cell lines. The biosurfactant BioEG was shown to be more active than surfactin against the studied breast cancer cells. The results gathered in this work are very promising regarding the biosurfactants potential for breast cancer treatment and encourage further work with the BioEG glycoprotein.

  15. Knowledge and opinions on oncoplastic surgery among breast and plastic surgeons

    DEFF Research Database (Denmark)

    Carstensen, Lena; Rose, Michael; Bentzon, Niels

    2015-01-01

    symmetrisation procedures were performed by plastic surgeons. Breast surgeons had sought more specific education, both international observerships and specific courses. In both groups of surgeons, the majority expressed that both tumour removal and reconstruction should be performed by doctors of their own...... of implementation of OPS in Denmark. METHODS: An electronic questionnaire was sent to breast and plastic surgeons performing breast cancer treatment. The questionnaire included demographics, education, experience with operative procedures and opinions on OPS. RESULTS: The questionnaire was sent to 50 breast...

  16. Isolation and identification of marine fish tumour (odontoma associated bacteria

    Directory of Open Access Journals (Sweden)

    Ramalingam Vijayakumar

    2015-09-01

    Full Text Available Objective: To identify fish tumour associated bacteria. Methods: The marine fish Sphyraena jello with odontoma was collected from in Tamil Nadu (Southeast India, and tumour associated bacteria were isolated. Then the isolated bacteria were identified based on molecular characters. Results: A total of 4 different bacterial species were isolated from tumour tissue. The bacterial species were Bacillus sp., Pontibacter sp., Burkholderia sp. and Macrococcus sp., and the sequences were submitted in DNA Data Bank of Japan with accession numbers of AB859240, AB859241, AB859242 and AB859243 respectively. Conclusions: Four different bacterial species were isolated from Sphyraena jello, but the role of bacteria within tumour needs to be further investigated.

  17. The Z-isomer of 11β-methoxy-17α-[123I]iodovinylestradiol is a promising radioligand for estrogen receptor imaging in human breast cancer

    International Nuclear Information System (INIS)

    Rijks, Leonie J. M.; Boer, Gerard J.; Endert, Erik; Bruin, Kora de; Janssen, Anton G. M.; Royen, Eric A. van

    1997-01-01

    The potential of both stereoisomers of 11β-methoxy-17α-[ 123 I]iodovinylestradiol (E- and Z-[ 123 I]MIVE) as suitable radioligands for imaging of estrogen receptor(ER)-positive human breast tumours was studied. The 17α-[ 123 I]iodovinylestradiol derivatives were prepared stereospecifically by oxidative radioiododestannylation of the corresponding 17α-tri-n-butylstannylvinylestradiol precursors. Both isomers of MIVE showed high in vitro affinity for dimethylbenzanthracene-induced rat and fresh human mammary tumour ER, that of Z-MIVE however being manyfold higher than that of E-MIVE. In vivo distribution studies with E- and Z-[ 123 I]MIVE in normal and tumour-bearing female rats showed ER-mediated uptake and retention in uterus, ovaries, pituitary, hypothalamus and mammary tumours, again the highest for Z-[ 123 I]MIVE. The uterus- and tumour-to-nontarget tissue (fat, muscle) uptake ratios were also highest for Z-[ 123 I]MIVE. Additionally, planar whole body imaging of two breast cancer patients 1-2 h after injection of Z-[ 123 I]MIVE showed increased focal uptake at known tumour sites. Therefore, we conclude that Z-[ 123 I]MIVE is a promising radioligand for the diagnostic imaging of ER in human breast cancer

  18. Alternative splicing enriched cDNA libraries identify breast cancer-associated transcripts

    Science.gov (United States)

    2010-01-01

    Background Alternative splicing (AS) is a central mechanism in the generation of genomic complexity and is a major contributor to transcriptome and proteome diversity. Alterations of the splicing process can lead to deregulation of crucial cellular processes and have been associated with a large spectrum of human diseases. Cancer-associated transcripts are potential molecular markers and may contribute to the development of more accurate diagnostic and prognostic methods and also serve as therapeutic targets. Alternative splicing-enriched cDNA libraries have been used to explore the variability generated by alternative splicing. In this study, by combining the use of trapping heteroduplexes and RNA amplification, we developed a powerful approach that enables transcriptome-wide exploration of the AS repertoire for identifying AS variants associated with breast tumor cells modulated by ERBB2 (HER-2/neu) oncogene expression. Results The human breast cell line (C5.2) and a pool of 5 ERBB2 over-expressing breast tumor samples were used independently for the construction of two AS-enriched libraries. In total, 2,048 partial cDNA sequences were obtained, revealing 214 alternative splicing sequence-enriched tags (ASSETs). A subset with 79 multiple exon ASSETs was compared to public databases and reported 138 different AS events. A high success rate of RT-PCR validation (94.5%) was obtained, and 2 novel AS events were identified. The influence of ERBB2-mediated expression on AS regulation was evaluated by capillary electrophoresis and probe-ligation approaches in two mammary cell lines (Hb4a and C5.2) expressing different levels of ERBB2. The relative expression balance between AS variants from 3 genes was differentially modulated by ERBB2 in this model system. Conclusions In this study, we presented a method for exploring AS from any RNA source in a transcriptome-wide format, which can be directly easily adapted to next generation sequencers. We identified AS transcripts

  19. Fine mapping of breast cancer genome-wide association studies loci in women of African ancestry identifies novel susceptibility markers.

    Science.gov (United States)

    Zheng, Yonglan; Ogundiran, Temidayo O; Falusi, Adeyinka G; Nathanson, Katherine L; John, Esther M; Hennis, Anselm J M; Ambs, Stefan; Domchek, Susan M; Rebbeck, Timothy R; Simon, Michael S; Nemesure, Barbara; Wu, Suh-Yuh; Leske, Maria Cristina; Odetunde, Abayomi; Niu, Qun; Zhang, Jing; Afolabi, Chibuzor; Gamazon, Eric R; Cox, Nancy J; Olopade, Christopher O; Olopade, Olufunmilayo I; Huo, Dezheng

    2013-07-01

    Numerous single nucleotide polymorphisms (SNPs) associated with breast cancer susceptibility have been identified by genome-wide association studies (GWAS). However, these SNPs were primarily discovered and validated in women of European and Asian ancestry. Because linkage disequilibrium is ancestry-dependent and heterogeneous among racial/ethnic populations, we evaluated common genetic variants at 22 GWAS-identified breast cancer susceptibility loci in a pooled sample of 1502 breast cancer cases and 1378 controls of African ancestry. None of the 22 GWAS index SNPs could be validated, challenging the direct generalizability of breast cancer risk variants identified in Caucasians or Asians to other populations. Novel breast cancer risk variants for women of African ancestry were identified in regions including 5p12 (odds ratio [OR] = 1.40, 95% confidence interval [CI] = 1.11-1.76; P = 0.004), 5q11.2 (OR = 1.22, 95% CI = 1.09-1.36; P = 0.00053) and 10p15.1 (OR = 1.22, 95% CI = 1.08-1.38; P = 0.0015). We also found positive association signals in three regions (6q25.1, 10q26.13 and 16q12.1-q12.2) previously confirmed by fine mapping in women of African ancestry. In addition, polygenic model indicated that eight best markers in this study, compared with 22 GWAS-identified SNPs, could better predict breast cancer risk in women of African ancestry (per-allele OR = 1.21, 95% CI = 1.16-1.27; P = 9.7 × 10(-16)). Our results demonstrate that fine mapping is a powerful approach to better characterize the breast cancer risk alleles in diverse populations. Future studies and new GWAS in women of African ancestry hold promise to discover additional variants for breast cancer susceptibility with clinical implications throughout the African diaspora.

  20. A review of biomechanically informed breast image registration

    International Nuclear Information System (INIS)

    Hipwell, John H; Vavourakis, Vasileios; Mertzanidou, Thomy; Eiben, Björn; Hawkes, David J; Han, Lianghao

    2016-01-01

    Breast radiology encompasses the full range of imaging modalities from routine imaging via x-ray mammography, magnetic resonance imaging and ultrasound (both two- and three-dimensional), to more recent technologies such as digital breast tomosynthesis, and dedicated breast imaging systems for positron emission mammography and ultrasound tomography. In addition new and experimental modalities, such as Photoacoustics, Near Infrared Spectroscopy and Electrical Impedance Tomography etc, are emerging. The breast is a highly deformable structure however, and this greatly complicates visual comparison of imaging modalities for the purposes of breast screening, cancer diagnosis (including image guided biopsy), tumour staging, treatment monitoring, surgical planning and simulation of the effects of surgery and wound healing etc. Due primarily to the challenges posed by these gross, non-rigid deformations, development of automated methods which enable registration, and hence fusion, of information within and across breast imaging modalities, and between the images and the physical space of the breast during interventions, remains an active research field which has yet to translate suitable methods into clinical practice. This review describes current research in the field of breast biomechanical modelling and identifies relevant publications where the resulting models have been incorporated into breast image registration and simulation algorithms. Despite these developments there remain a number of issues that limit clinical application of biomechanical modelling. These include the accuracy of constitutive modelling, implementation of representative boundary conditions, failure to meet clinically acceptable levels of computational cost, challenges associated with automating patient-specific model generation (i.e. robust image segmentation and mesh generation) and the complexity of applying biomechanical modelling methods in routine clinical practice. (topical review)

  1. Improved prognostic classification of breast cancer defined by antagonistic activation patterns of immune response pathway modules

    International Nuclear Information System (INIS)

    Teschendorff, Andrew E; Gomez, Sergio; Arenas, Alex; El-Ashry, Dorraya; Schmidt, Marcus; Gehrmann, Mathias; Caldas, Carlos

    2010-01-01

    Elucidating the activation pattern of molecular pathways across a given tumour type is a key challenge necessary for understanding the heterogeneity in clinical response and for developing novel more effective therapies. Gene expression signatures of molecular pathway activation derived from perturbation experiments in model systems as well as structural models of molecular interactions ('model signatures') constitute an important resource for estimating corresponding activation levels in tumours. However, relatively few strategies for estimating pathway activity from such model signatures exist and only few studies have used activation patterns of pathways to refine molecular classifications of cancer. Here we propose a novel network-based method for estimating pathway activation in tumours from model signatures. We find that although the pathway networks inferred from cancer expression data are highly consistent with the prior information contained in the model signatures, that they also exhibit a highly modular structure and that estimation of pathway activity is dependent on this modular structure. We apply our methodology to a panel of 438 estrogen receptor negative (ER-) and 785 estrogen receptor positive (ER+) breast cancers to infer activation patterns of important cancer related molecular pathways. We show that in ER negative basal and HER2+ breast cancer, gene expression modules reflecting T-cell helper-1 (Th1) and T-cell helper-2 (Th2) mediated immune responses play antagonistic roles as major risk factors for distant metastasis. Using Boolean interaction Cox-regression models to identify non-linear pathway combinations associated with clinical outcome, we show that simultaneous high activation of Th1 and low activation of a TGF-beta pathway module defines a subtype of particularly good prognosis and that this classification provides a better prognostic model than those based on the individual pathways. In ER+ breast cancer, we find that

  2. Quantifying the number of lymph nodes identified in one-stage versus two-stage axillary dissection in breast cancer

    DEFF Research Database (Denmark)

    Damgaard, Olaf E; Jensen, Maj-Britt; Kroman, Niels

    2013-01-01

    To establish whether a different number of lymph nodes is identified in a delayed versus an immediate axillary lymph node dissection (ALND) in breast cancer patients.......To establish whether a different number of lymph nodes is identified in a delayed versus an immediate axillary lymph node dissection (ALND) in breast cancer patients....

  3. The curability of breast cancer and the treatment of advanced disease

    International Nuclear Information System (INIS)

    Guarneri, Valentina; Conte, Pier Franco

    2004-01-01

    Breast cancer represents a major health problem, with more than 1,000,000 new cases and 370,000 deaths yearly worldwide. In the last decade, in spite of an increasing incidence, breast cancer mortality has been declining in the majority of developed countries. This is the combined result of better education, widespread screening programmes and more efficacious adjuvant treatments. Better knowledge of breast cancer biology now allows the cosmetic, physical and psychological consequences of radical mastectomy to be spared in the majority of breast cancer patients. Use of the sentinel node technique is rapidly expanding and this will further reduce the extent and the consequences of surgery. Several clinico-pathological factors are used to discriminate between patients at low (<10%), average (10-40%) and high risk of relapse. Nodal status, tumour size, tumour grade and age are accepted universally as important factors to define risk categories. Newer factors such as uPA/PAI-1, HERer2-neu, proliferative indices and gene expression profile are promising and will allow better discrimination between patients at different risk. Endocrine manipulation with tamoxifen, ovarian ablation or both is the preferred option in the case of endocrine-responsive tumours. Tamoxifen administered for 5 years is the standard treatment for postmenopausal patients; tamoxifen plus ovarian ablation is more effective than tamoxifen alone for premenopausal women. Recent data demonstrate that, for postmenopausal patients, the aromatase inhibitors are superior to tamoxifen, with a different safety profile. At present, anastrozole can be used in the adjuvant setting in cases of tamoxifen intolerance or toxicity. Chemotherapy is the treatment of choice for steroid receptor-negative tumours. Polychemotherapy is superior to single agents and anthracycline-containing regimens are superior to CMF. Six courses of FEC or FAC or the sequential administration of four doses of anthracycline followed by four

  4. The curability of breast cancer and the treatment of advanced disease

    Energy Technology Data Exchange (ETDEWEB)

    Guarneri, Valentina; Conte, Pier Franco [Department of Oncology and Hematology, University of Modena and Reggio Emilia, Modena (Italy)

    2004-06-01

    Breast cancer represents a major health problem, with more than 1,000,000 new cases and 370,000 deaths yearly worldwide. In the last decade, in spite of an increasing incidence, breast cancer mortality has been declining in the majority of developed countries. This is the combined result of better education, widespread screening programmes and more efficacious adjuvant treatments. Better knowledge of breast cancer biology now allows the cosmetic, physical and psychological consequences of radical mastectomy to be spared in the majority of breast cancer patients. Use of the sentinel node technique is rapidly expanding and this will further reduce the extent and the consequences of surgery. Several clinico-pathological factors are used to discriminate between patients at low (<10%), average (10-40%) and high risk of relapse. Nodal status, tumour size, tumour grade and age are accepted universally as important factors to define risk categories. Newer factors such as uPA/PAI-1, HERer2-neu, proliferative indices and gene expression profile are promising and will allow better discrimination between patients at different risk. Endocrine manipulation with tamoxifen, ovarian ablation or both is the preferred option in the case of endocrine-responsive tumours. Tamoxifen administered for 5 years is the standard treatment for postmenopausal patients; tamoxifen plus ovarian ablation is more effective than tamoxifen alone for premenopausal women. Recent data demonstrate that, for postmenopausal patients, the aromatase inhibitors are superior to tamoxifen, with a different safety profile. At present, anastrozole can be used in the adjuvant setting in cases of tamoxifen intolerance or toxicity. Chemotherapy is the treatment of choice for steroid receptor-negative tumours. Polychemotherapy is superior to single agents and anthracycline-containing regimens are superior to CMF. Six courses of FEC or FAC or the sequential administration of four doses of anthracycline followed by four

  5. Awareness and current knowledge of breast cancer.

    Science.gov (United States)

    Akram, Muhammad; Iqbal, Mehwish; Daniyal, Muhammad; Khan, Asmat Ullah

    2017-10-02

    Breast cancer remains a worldwide public health dilemma and is currently the most common tumour in the globe. Awareness of breast cancer, public attentiveness, and advancement in breast imaging has made a positive impact on recognition and screening of breast cancer. Breast cancer is life-threatening disease in females and the leading cause of mortality among women population. For the previous two decades, studies related to the breast cancer has guided to astonishing advancement in our understanding of the breast cancer, resulting in further proficient treatments. Amongst all the malignant diseases, breast cancer is considered as one of the leading cause of death in post menopausal women accounting for 23% of all cancer deaths. It is a global issue now, but still it is diagnosed in their advanced stages due to the negligence of women regarding the self inspection and clinical examination of the breast. This review addresses anatomy of the breast, risk factors, epidemiology of breast cancer, pathogenesis of breast cancer, stages of breast cancer, diagnostic investigations and treatment including chemotherapy, surgery, targeted therapies, hormone replacement therapy, radiation therapy, complementary therapies, gene therapy and stem-cell therapy etc for breast cancer.

  6. Elastic moduli of normal and pathological human breast tissues: an inversion-technique-based investigation of 169 samples

    Science.gov (United States)

    Samani, Abbas; Zubovits, Judit; Plewes, Donald

    2007-03-01

    Understanding and quantifying the mechanical properties of breast tissues has been a subject of interest for the past two decades. This has been motivated in part by interest in modelling soft tissue response for surgery planning and virtual-reality-based surgical training. Interpreting elastography images for diagnostic purposes also requires a sound understanding of normal and pathological tissue mechanical properties. Reliable data on tissue elastic properties are very limited and those which are available tend to be inconsistent, in part as a result of measurement methodology. We have developed specialized techniques to measure tissue elasticity of breast normal tissues and tumour specimens and applied them to 169 fresh ex vivo breast tissue samples including fat and fibroglandular tissue as well as a range of benign and malignant breast tumour types. Results show that, under small deformation conditions, the elastic modulus of normal breast fat and fibroglandular tissues are similar while fibroadenomas were approximately twice the stiffness. Fibrocystic disease and malignant tumours exhibited a 3-6-fold increased stiffness with high-grade invasive ductal carcinoma exhibiting up to a 13-fold increase in stiffness compared to fibrogalndular tissue. A statistical analysis showed that differences between the elastic modulus of the majority of those tissues were statistically significant. Implications for the specificity advantages of elastography are reviewed.

  7. Elastic moduli of normal and pathological human breast tissues: an inversion-technique-based investigation of 169 samples

    International Nuclear Information System (INIS)

    Samani, Abbas; Zubovits, Judit; Plewes, Donald

    2007-01-01

    Understanding and quantifying the mechanical properties of breast tissues has been a subject of interest for the past two decades. This has been motivated in part by interest in modelling soft tissue response for surgery planning and virtual-reality-based surgical training. Interpreting elastography images for diagnostic purposes also requires a sound understanding of normal and pathological tissue mechanical properties. Reliable data on tissue elastic properties are very limited and those which are available tend to be inconsistent, in part as a result of measurement methodology. We have developed specialized techniques to measure tissue elasticity of breast normal tissues and tumour specimens and applied them to 169 fresh ex vivo breast tissue samples including fat and fibroglandular tissue as well as a range of benign and malignant breast tumour types. Results show that, under small deformation conditions, the elastic modulus of normal breast fat and fibroglandular tissues are similar while fibroadenomas were approximately twice the stiffness. Fibrocystic disease and malignant tumours exhibited a 3-6-fold increased stiffness with high-grade invasive ductal carcinoma exhibiting up to a 13-fold increase in stiffness compared to fibrogalndular tissue. A statistical analysis showed that differences between the elastic modulus of the majority of those tissues were statistically significant. Implications for the specificity advantages of elastography are reviewed

  8. Elastic moduli of normal and pathological human breast tissues: an inversion-technique-based investigation of 169 samples

    Energy Technology Data Exchange (ETDEWEB)

    Samani, Abbas [Department of Medical Biophysics/Electrical and Computer Engineering, University of Western Ontario, Medical Sciences Building, London, Ontario, N6A 5C1 (Canada); Zubovits, Judit [Department of Anatomic Pathology, Sunnybrook Health Sciences Centre, 2075 Bayview Avenue, Toronto, Ontario, M4N 3M5 (Canada); Plewes, Donald [Department of Medical Biophysics, University of Toronto, 2075 Bayview Avenue, Toronto, Ontario, M4N 3M5 (Canada)

    2007-03-21

    Understanding and quantifying the mechanical properties of breast tissues has been a subject of interest for the past two decades. This has been motivated in part by interest in modelling soft tissue response for surgery planning and virtual-reality-based surgical training. Interpreting elastography images for diagnostic purposes also requires a sound understanding of normal and pathological tissue mechanical properties. Reliable data on tissue elastic properties are very limited and those which are available tend to be inconsistent, in part as a result of measurement methodology. We have developed specialized techniques to measure tissue elasticity of breast normal tissues and tumour specimens and applied them to 169 fresh ex vivo breast tissue samples including fat and fibroglandular tissue as well as a range of benign and malignant breast tumour types. Results show that, under small deformation conditions, the elastic modulus of normal breast fat and fibroglandular tissues are similar while fibroadenomas were approximately twice the stiffness. Fibrocystic disease and malignant tumours exhibited a 3-6-fold increased stiffness with high-grade invasive ductal carcinoma exhibiting up to a 13-fold increase in stiffness compared to fibrogalndular tissue. A statistical analysis showed that differences between the elastic modulus of the majority of those tissues were statistically significant. Implications for the specificity advantages of elastography are reviewed.

  9. Cdx2 Polymorphism Affects the Activities of Vitamin D Receptor in Human Breast Cancer Cell Lines and Human Breast Carcinomas

    Science.gov (United States)

    Di Benedetto, Anna; Korita, Etleva; Goeman, Frauke; Sacconi, Andrea; Biagioni, Francesca; Blandino, Giovanni; Strano, Sabrina; Muti, Paola; Mottolese, Marcella; Falvo, Elisabetta

    2015-01-01

    Vitamin D plays a role in cancer development and acts through the vitamin D receptor (VDR). It regulates the action of hormone responsive genes and is involved in cell cycle regulation, differentiation and apoptosis. VDR is a critical component of the vitamin D pathway and different common single nucleotide polymorphisms have been identified. Cdx2 VDR polymorphism can play an important role in breast cancer, modulating the activity of VDR. The objective of this study is to assess the relationship between the Cdx2 VDR polymorphism and the activities of VDR in human breast cancer cell lines and carcinomas breast patients. Cdx2 VDR polymorphism and antiproliferative effects of vitamin D treatment were investigated in a panel of estrogen receptor-positive (MCF7 and T-47D) and estrogen receptor-negative (MDA-MB-231, SUM 159PT, SK-BR-3, BT549, MDA-MB-468, HCC1143, BT20 and HCC1954) human breast cancer cell lines. Furthermore, the potential relationship among Cdx2 VDR polymorphism and a number of biomarkers used in clinical management of breast cancer was assessed in an ad hoc set of breast cancer cases. Vitamin D treatment efficacy was found to be strongly dependent on the Cdx2 VDR status in ER-negative breast cancer cell lines tested. In our series of breast cancer cases, the results indicated that patients with variant homozygote AA were associated with bio-pathological characteristics typical of more aggressive tumours, such as ER negative, HER2 positive and G3. Our results may suggest a potential effect of Cdx2 VDR polymorphism on the efficacy of vitamin D treatment in aggressive breast cancer cells (estrogen receptor negative). These results suggest that Cdx2 polymorphism may be a potential biomarker for vitamin D treatment in breast cancer, independently of the VDR receptor expression. PMID:25849303

  10. Cdx2 polymorphism affects the activities of vitamin D receptor in human breast cancer cell lines and human breast carcinomas.

    Directory of Open Access Journals (Sweden)

    Claudio Pulito

    Full Text Available Vitamin D plays a role in cancer development and acts through the vitamin D receptor (VDR. It regulates the action of hormone responsive genes and is involved in cell cycle regulation, differentiation and apoptosis. VDR is a critical component of the vitamin D pathway and different common single nucleotide polymorphisms have been identified. Cdx2 VDR polymorphism can play an important role in breast cancer, modulating the activity of VDR. The objective of this study is to assess the relationship between the Cdx2 VDR polymorphism and the activities of VDR in human breast cancer cell lines and carcinomas breast patients. Cdx2 VDR polymorphism and antiproliferative effects of vitamin D treatment were investigated in a panel of estrogen receptor-positive (MCF7 and T-47D and estrogen receptor-negative (MDA-MB-231, SUM 159PT, SK-BR-3, BT549, MDA-MB-468, HCC1143, BT20 and HCC1954 human breast cancer cell lines. Furthermore, the potential relationship among Cdx2 VDR polymorphism and a number of biomarkers used in clinical management of breast cancer was assessed in an ad hoc set of breast cancer cases. Vitamin D treatment efficacy was found to be strongly dependent on the Cdx2 VDR status in ER-negative breast cancer cell lines tested. In our series of breast cancer cases, the results indicated that patients with variant homozygote AA were associated with bio-pathological characteristics typical of more aggressive tumours, such as ER negative, HER2 positive and G3. Our results may suggest a potential effect of Cdx2 VDR polymorphism on the efficacy of vitamin D treatment in aggressive breast cancer cells (estrogen receptor negative. These results suggest that Cdx2 polymorphism may be a potential biomarker for vitamin D treatment in breast cancer, independently of the VDR receptor expression.

  11. MRI appearances of borderline ovarian tumours

    Energy Technology Data Exchange (ETDEWEB)

    Bent, C.L. [Department of Diagnostic Imaging, St Bartholomew' s Hospital, West Smithfield, London (United Kingdom)], E-mail: clare.bent@bartsandthelondon.nhs.uk; Sahdev, A.; Rockall, A.G. [Department of Diagnostic Imaging, St Bartholomew' s Hospital, West Smithfield, London (United Kingdom); Singh, N. [Department of Pathology, St Bartholomew' s Hospital, West Smithfield, London (United Kingdom); Sohaib, S.A. [Department of Radiology, Royal Marsden Hospital, London (United Kingdom); Reznek, R.H. [Cancer Imaging, St Bartholomew' s Hospital, West Smithfield, London (United Kingdom)

    2009-04-15

    This review was performed to describe the range of magnetic resonance imaging (MRI) appearances of borderline ovarian tumours. The MRI findings in 26 patients with 31 borderline ovarian tumours (mean age: 40.1 years, range: 14-85 years) were retrospectively reviewed. For each tumour, site, size, MRI characteristics, and enhancement following gadolinium administration were recorded. There were 20 serous and 11 mucinous borderline ovarian subtypes. Nine of 26 patients demonstrated bilateral disease on MRI; synchronous contralateral ovarian disease included three benign, five serous borderline, and one serous invasive tumour. A history of a metachronous mucinous borderline tumour was identified in one patient. MRI appearances were classified into four morphological categories: group 1 (6/31, 19%), unilocular cysts; group 2 (6/31, 19%), minimally septate cysts with papillary projections; group 3 (14/31, 45%), markedly septate lesions with plaque-like excrescences; and group 4 (5/31, 16%), predominantly solid with exophytic papillary projections, all of serous subtype. There was a significant difference in mean volume between serous (841.5 cm{sup 3}) and mucinous (6358.2 cm{sup 3}) subtypes (p = 0.009). All tumours demonstrated at least one MRI feature suggestive of malignancy. The present review demonstrates the variable MRI appearances of borderline ovarian tumours along with imaging features suggestive of tumour subtype. In patients in whom the clinical features are suggestive of a borderline ovarian tumour (young age and normal or minimally elevated CA125), the ability to predict a borderline disease using morphological features observed on MRI would be extremely helpful in surgical planning, with the potential to offer fertility or ovary-preserving surgery. Future studies are required to further this aim.

  12. Gastric metastases originating from occult breast lobular carcinoma: diagnostic and therapeutic problems

    Directory of Open Access Journals (Sweden)

    Russo Leila

    2008-07-01

    Full Text Available Abstract Background Breast cancer is the most frequent malignant tumour to metastasize into the gastrointestinal tract in female and is second only to malignant melanoma. Nevertheless gastrointestinal metastases arising from breast cancer are quite rare. The upper gastrointestinal tract is more frequently involved and lobular infiltrating carcinoma has a greater predilection compared to the ductal type. Case presentation The authors describe the case of a 70 years old woman with a preoperative diagnosis of gastric undifferentiated medullary – type carcinoma, which was the first manifestation of an occult breast carcinoma. The primary site of carcinoma was identified with the use of a panel of selected immunohistochemical markers. Conclusion Our goal in this case report is to increase the awareness of surgeons and clinicians to rule out the possibility of mammary origin in circumstance of gastric cancer occurring in female, even in patients without a previous or concurrent history of breast carcinoma. Although not a particularly common event, it is, nevertheless, reported in the literature. The differentiation between primary gastric carcinoma and metastatic breast carcinoma is essential for planning the correct therapeutic approach, in order to avoid the patient unnecessary surgery.

  13. Klinefelter's syndrome associated with breast carcinoma and Paget's disease of the nipple.

    Science.gov (United States)

    Moshakis, V; Fordyce, M J; Griffiths, J D

    1983-09-01

    We describe a patient with Klinefelter's syndrome associated with multi-focal breast carcinoma and Paget's disease of the nipple. Reviewing the 16 previously documented cases in the world literature, it is apparent that patients with this syndrome have an increased incidence of breast carcinoma. There is no evidence to date to suggest that such tumour is morphologically or biologically different from breast cancer in females and normal men.

  14. Genome-wide association study identifies multiple loci associated with both mammographic density and breast cancer risk

    Science.gov (United States)

    Lindström, Sara; Thompson, Deborah J.; Paterson, Andrew D.; Li, Jingmei; Gierach, Gretchen L.; Scott, Christopher; Stone, Jennifer; Douglas, Julie A.; dos-Santos-Silva, Isabel; Fernandez-Navarro, Pablo; Verghase, Jajini; Smith, Paula; Brown, Judith; Luben, Robert; Wareham, Nicholas J.; Loos, Ruth J.F.; Heit, John A.; Pankratz, V. Shane; Norman, Aaron; Goode, Ellen L.; Cunningham, Julie M.; deAndrade, Mariza; Vierkant, Robert A.; Czene, Kamila; Fasching, Peter A.; Baglietto, Laura; Southey, Melissa C.; Giles, Graham G.; Shah, Kaanan P.; Chan, Heang-Ping; Helvie, Mark A.; Beck, Andrew H.; Knoblauch, Nicholas W.; Hazra, Aditi; Hunter, David J.; Kraft, Peter; Pollan, Marina; Figueroa, Jonine D.; Couch, Fergus J.; Hopper, John L.; Hall, Per; Easton, Douglas F.; Boyd, Norman F.; Vachon, Celine M.; Tamimi, Rulla M.

    2015-01-01

    Mammographic density reflects the amount of stromal and epithelial tissues in relation to adipose tissue in the breast and is a strong risk factor for breast cancer. Here we report the results from meta-analysis of genome-wide association studies (GWAS) of three mammographic density phenotypes: dense area, non-dense area and percent density in up to 7,916 women in stage 1 and an additional 10,379 women in stage 2. We identify genome-wide significant (P<5×10−8) loci for dense area (AREG, ESR1, ZNF365, LSP1/TNNT3, IGF1, TMEM184B, SGSM3/MKL1), non-dense area (8p11.23) and percent density (PRDM6, 8p11.23, TMEM184B). Four of these regions are known breast cancer susceptibility loci, and four additional regions were found to be associated with breast cancer (P<0.05) in a large meta-analysis. These results provide further evidence of a shared genetic basis between mammographic density and breast cancer and illustrate the power of studying intermediate quantitative phenotypes to identify putative disease susceptibility loci. PMID:25342443

  15. Use of deep whole-genome sequencing data to identify structure risk variants in breast cancer susceptibility genes.

    Science.gov (United States)

    Guo, Xingyi; Shi, Jiajun; Cai, Qiuyin; Shu, Xiao-Ou; He, Jing; Wen, Wanqing; Allen, Jamie; Pharoah, Paul; Dunning, Alison; Hunter, David J; Kraft, Peter; Easton, Douglas F; Zheng, Wei; Long, Jirong

    2018-03-01

    Functional disruptions of susceptibility genes by large genomic structure variant (SV) deletions in germlines are known to be associated with cancer risk. However, few studies have been conducted to systematically search for SV deletions in breast cancer susceptibility genes. We analysed deep (> 30x) whole-genome sequencing (WGS) data generated in blood samples from 128 breast cancer patients of Asian and European descent with either a strong family history of breast cancer or early cancer onset disease. To identify SV deletions in known or suspected breast cancer susceptibility genes, we used multiple SV calling tools including Genome STRiP, Delly, Manta, BreakDancer and Pindel. SV deletions were detected by at least three of these bioinformatics tools in five genes. Specifically, we identified heterozygous deletions covering a fraction of the coding regions of BRCA1 (with approximately 80kb in two patients), and TP53 genes (with ∼1.6 kb in two patients), and of intronic regions (∼1 kb) of the PALB2 (one patient), PTEN (three patients) and RAD51C genes (one patient). We confirmed the presence of these deletions using real-time quantitative PCR (qPCR). Our study identified novel SV deletions in breast cancer susceptibility genes and the identification of such SV deletions may improve clinical testing.

  16. Sentinel node lymphoscintigraphy in breast cancer: problems, solutions and clinical utility

    International Nuclear Information System (INIS)

    Wye, D.A.; Cohn, D.; Evans, S.G.; Larcos, G.; Ung, O.; Barry, P.

    1999-01-01

    Full text: Axillary lymph node status is an essential element in the staging of breast cancer. Recently, lymphatic mapping and sentinel node (SN) identification with lymphoscintigraphy has been promoted. The purposes of this study were to determine: (1) factors important in optimal identification of SNs preoperatively and (2) accuracy of SNs in predicting axillary lymph node status. Lymphoscintigraphy using 99 Tc m -antimony trisulphide colloid was performed in 35 patients before axillary dissection surgery. Four injections (20 MBq in 0.5 ml) were administered either around the biopsy cavity/scar or peritumorally. Sequential images in the anterior, anterior oblique and lateral projections were obtained until a SN was identified and in some patients delayed images (up to 15 h) were required. SNs were marked on the patient's skin in two planes. During surgery, a hand-held gamma probe was used to localize the marked SNs, which were removed prior to complete axillary dissection. Dissected lymph nodes were evaluated histopathologically for tumour involvement. To optimize SN identification, we found that breast cleaning post-injection, breast massage, imaging with arms both raised and lowered, and using different symbols to mark multiple SNs were necessary. In 32/35 patients (91%), a SN was successfully identified. Drainage patterns varied and were primarily to the axilla, internal mammary chain and intra clavicular areas. The SN appears to be an accurate predictor of axillary node status. In conclusion, breast lymphoscintigraphy is a simple procedure which appears to accurately identify sentinel nodes

  17. Receptor conversion in distant breast cancer metastases

    NARCIS (Netherlands)

    Hoefnagel, L.D.C.

    2013-01-01

    The routine pathological work-up of breast cancer includes the evaluation of the estrogen receptor (ERα), progesterone receptor (PR) and human epidermal growth factor receptor 2 (HER2) which reveals biological information about the tumour as well as provides predictive biomarkers regarding hormonal

  18. Pregnancy after treatment of breast cancer--a population-based study on behalf of Danish Breast Cancer Cooperative Group

    DEFF Research Database (Denmark)

    Kroman, N.; Jensen, M.B.; Wohlfahrt, J.

    2008-01-01

    , 10 236 women with primary breast cancer aged 45 years or less at the time of diagnosis were followed for 95 616 person years. Among these, 371 women experienced pregnancy after treatment of breast cancer. In a multivariate analysis that included age at diagnosis, stage of disease, and pregnancy...... history prior to diagnosis, women who had a full-term pregnancy subsequent to breast cancer treatment were found to have a reduced risk of dying (relative risk: 0.73; 95% confidence interval: 0.54-0.99) compared with other women with breast cancer. The effect was not significantly modified by age...... at diagnosis, tumour size, nodal status, or pregnancy history before diagnosis of breast cancer. Neither spontaneous abortions nor induced abortions subsequent to breast cancer treatment had a negative impact on prognosis. CONCLUSION: In line with our previous study, but based on more than twice the patient...

  19. Exome sequencing identifies rare deleterious mutations in DNA repair genes FANCC and BLM as potential breast cancer susceptibility alleles.

    Directory of Open Access Journals (Sweden)

    Ella R Thompson

    2012-09-01

    Full Text Available Despite intensive efforts using linkage and candidate gene approaches, the genetic etiology for the majority of families with a multi-generational breast cancer predisposition is unknown. In this study, we used whole-exome sequencing of thirty-three individuals from 15 breast cancer families to identify potential predisposing genes. Our analysis identified families with heterozygous, deleterious mutations in the DNA repair genes FANCC and BLM, which are responsible for the autosomal recessive disorders Fanconi Anemia and Bloom syndrome. In total, screening of all exons in these genes in 438 breast cancer families identified three with truncating mutations in FANCC and two with truncating mutations in BLM. Additional screening of FANCC mutation hotspot exons identified one pathogenic mutation among an additional 957 breast cancer families. Importantly, none of the deleterious mutations were identified among 464 healthy controls and are not reported in the 1,000 Genomes data. Given the rarity of Fanconi Anemia and Bloom syndrome disorders among Caucasian populations, the finding of multiple deleterious mutations in these critical DNA repair genes among high-risk breast cancer families is intriguing and suggestive of a predisposing role. Our data demonstrate the utility of intra-family exome-sequencing approaches to uncover cancer predisposition genes, but highlight the major challenge of definitively validating candidates where the incidence of sporadic disease is high, germline mutations are not fully penetrant, and individual predisposition genes may only account for a tiny proportion of breast cancer families.

  20. Enhancer of the rudimentary gene homologue (ERH expression pattern in sporadic human breast cancer and normal breast tissue

    Directory of Open Access Journals (Sweden)

    Knüchel Ruth

    2008-05-01

    Full Text Available Abstract Background The human gene ERH (Enhancer of the Rudimentary gene Homologue has previously been identified by in silico analysis of four million ESTs as a gene differentially expressed in breast cancer. The biological function of ERH protein has not been fully elucidated, however functions in cell cycle progression, pyrimidine metabolism a possible interaction with p21(Cip1/Waf1 via the Ciz1 zinc finger protein have been suggested. The aim of the present study was a systematic characterization of ERH expression in human breast cancer in order to evaluate possible clinical applications of this molecule. Methods The expression pattern of ERH was analyzed using multiple tissue northern blots (MTN on a panel of 16 normal human tissues and two sets of malignant/normal breast and ovarian tissue samples. ERH expression was further analyzed in breast cancer and normal breast tissues and in tumorigenic as well as non-tumorigenic breast cancer cell lines, using quantitative RT-PCR and non-radioisotopic in situ hybridization (ISH. Results Among normal human tissues, ERH expression was most abundant in testis, heart, ovary, prostate, and liver. In the two MTN sets of malignant/normal breast and ovarian tissue,ERH was clearly more abundantly expressed in all tumours than in normal tissue samples. Quantitative RT-PCR analyses showed that ERH expression was significantly more abundant in tumorigenic than in non-tumorigenic breast cancer cell lines (4.5-fold; p = 0.05, two-tailed Mann-Whitney U-test; the same trend was noted in a set of 25 primary invasive breast cancers and 16 normal breast tissue samples (2.5-fold; p = 0.1. These findings were further confirmed by non-radioisotopic ISH in human breast cancer and normal breast tissue. Conclusion ERH expression is clearly up-regulated in malignant as compared with benign breast cells both in primary human breast cancer and in cell models of breast cancer. Since similar results were obtained for ovarian

  1. Thyroid cancer in a patient with a germline MSH2 mutation. Case report and review of the Lynch syndrome expanding tumour spectrum

    Directory of Open Access Journals (Sweden)

    Stulp Rein P

    2008-02-01

    Full Text Available Abstract Lynch syndrome (HNPCC is a dominantly inherited disorder characterized by germline defects in DNA mismatch repair (MMR genes and the development of a variety of cancers, predominantly colorectal and endometrial. We present a 44-year-old woman who was shown to carry the truncating MSH2 gene mutation that had previously been identified in her family. Recently, she had been diagnosed with an undifferentiated carcinoma of the thyroid and an adenoma of her coecum. Although the thyroid carcinoma was not MSI-high (1 out of 5 microsatellites instable, it did show complete loss of immunohistochemical expression for the MSH2 protein, suggesting that this tumour was not coincidental. Although the risks for some tumour types, including breast cancer, soft tissue sarcoma and prostate cancer, are not significantly increased in Lynch syndrome, MMR deficiency in the presence of a corresponding germline defect has been demonstrated in incidental cases of a growing range of tumour types, which is reviewed in this paper. Interestingly, the MSH2-associated tumour spectrum appears to be wider than that of MLH1 and generally the risk for most extra-colonic cancers appears to be higher for MSH2 than for MLH1 mutation carriers. Together with a previously reported case, our findings show that anaplastic thyroid carcinoma can develop in the setting of Lynch syndrome. Uncommon Lynch syndrome-associated tumour types might be useful in the genetic analysis of a Lynch syndrome suspected family if samples from typical Lynch syndrome tumours are unavailable.

  2. Bilateral symmetry analysis of breast MRI

    International Nuclear Information System (INIS)

    Alterson, Robert; Plewes, Donald B

    2003-01-01

    Mammographic interpretation often uses symmetry between left and right breasts to indicate the site of potential tumour masses. This approach has not been applied to breast images obtained from MRI. We present an automatic technique for breast symmetry detection based on feature extraction techniques which does not require any efforts to co-register breast MRI data. The approach applies computer-vision techniques to detect natural biological symmetries in breast MR scans based on three objective measures of similarity: multiresolution non-orthogonal wavelet representation, three-dimensional intensity distributions and co-occurrence matrices. Statistical distributions that are invariant to feature localization are computed for each of the extracted image features. These distributions are later compared against each other to account for perceptual similarity. Studies based on 51 normal MRI scans of randomly selected patients showed that the sensitivity of symmetry detection rate approached 94%. The symmetry analysis procedure presented in this paper can be applied as an aid in detecting breast tissue changes arising from disease

  3. Intracapillary HbO2 saturations in murine tumours and human tumour xenografts measured by cryospectrophotometry: relationship to tumour volume, tumour pH and fraction of radiobiologically hypoxic cells.

    Science.gov (United States)

    Rofstad, E K; Fenton, B M; Sutherland, R M

    1988-05-01

    Frequency distributions for intracapillary HbO2 saturation were determined for two murine tumour lines (KHT, RIF-1) and two human ovarian carcinoma xenograft lines (MLS, OWI) using a cryospectrophotometric method. The aim was to search for possible relationships between HbO2 saturation status and tumour volume, tumour pH and fraction of radiobiologically hypoxic cells. Tumour pH was measured by 31P NMR spectroscopy. Hypoxic fractions were determined from cell survival curves for tumours irradiated in vivo and assayed in vitro. Tumours in the volume range 100-4000 mm3 were studied and the majority of the vessels were found to have HbO2 saturations below 10%. The volume-dependence of the HbO2 frequency distributions differed significantly among the four tumour lines; HbO2 saturation status decreased with increasing tumour volume for the KHT, RIF-1 and MLS lines and was independent of tumour volume for the OWI line. The data indicated that the rate of decrease in HbO2 saturation status during tumour growth was related to the rate of development of necrosis. The volume-dependence of tumour pH was very similar to that of the HbO2 saturation status for all tumour lines. Significant correlations were therefore found between HbO2 saturation status and tumour pH, both within tumour lines and across the four tumour lines, reflecting that the volume-dependence of both parameters probably was a compulsory consequence of reduced oxygen supply conditions during tumour growth. Hypoxic fraction increased during tumour growth for the KHT, RIF-1 and MLS lines and was volume-independent for the OWI line, suggesting a relationship between HbO2 saturation status and hypoxic fraction within tumour lines. However, there was no correlation between these two parameters across the four tumour lines, indicating that the hypoxic fraction of a tumour is not determined only by the oxygen supply conditions; other parameters may also be important, e.g. oxygen diffusivity, rate of oxygen

  4. Analysis of radiation-induced angiosarcoma of the breast.

    Science.gov (United States)

    Zemanova, M; Rauova, K; Boljesikova, E; Machalekova, K; Krajcovicova, I; Lehotska, V; Mikulova, M; Svec, J

    2014-01-01

    Breast angiosarcoma may occur de novo, or as a complication of radiation therapy, or chronic lymphedema secondary to axillary lymph node dissection for mammary carcinoma. Both primary and secondary angiosarcomas may present with bruise like skin discoloration, which may delay the diagnosis. Imaging findings are nonspecific. In case of high-grade tumours, MRI may be used effectively to determine lesion extent by showing rapid enhancement, nevertheless earliest possible diagnostics is crucial therefore any symptoms of angiosarcoma have to be carefully analysed. The case analysed here reports on results of 44-year old premenopausal woman who was treated for a T1N1M0 invasive ductal carcinoma. After a biopsy diagnosis of carcinoma, the patient underwent quadrantectomy with axillary lymph node dissection. She received partial 4 cycles of chemotherapy with adriamycin and cyclophosphamide, followed by radiation treatment. Thereafter, a standard postoperative radiotherapy was applied at our institution four months after chemotherapy (TD 46 Gy in 23 fractions followed by a 10 Gy electron boost to the tumour bed). Adjuvant chemotherapy was finished six months after operation, followed by tamoxifen. Follow up: no further complications were detected during regular check-ups. However, 12-years later, patient reported significant changes at breast region which was exposed to radiation during treatment of original tumour. In this article, we describe the clinical presentation, imaging and pathological findings of secondary angiosarcoma of the breast after radiotherapy (Fig. 2, Ref. 26).

  5. In situ immune response after neoadjuvant chemotherapy for breast cancer predicts survival.

    Science.gov (United States)

    Ladoire, Sylvain; Mignot, Grégoire; Dabakuyo, Sandrine; Arnould, Laurent; Apetoh, Lionel; Rébé, Cedric; Coudert, Bruno; Martin, Francois; Bizollon, Marie Hélène; Vanoli, André; Coutant, Charles; Fumoleau, Pierre; Bonnetain, Franck; Ghiringhelli, François

    2011-07-01

    Accumulating preclinical evidence suggests that anticancer immune responses contribute to the success of chemotherapy. However, the predictive value of tumour-infiltrating lymphocytes after neoadjuvant chemotherapy for breast cancer remains unknown. We hypothesized that the nature of the immune infiltrate following neoadjuvant chemotherapy would predict patient survival. In a series of 111 consecutive HER2- and a series of 51 non-HER2-overexpressing breast cancer patients treated by neoadjuvant chemotherapy, we studied by immunohistochemistry tumour infiltration by FOXP3 and CD8 T lymphocytes before and after chemotherapy. Kaplan-Meier analysis and Cox modelling were used to assess relapse-free survival (RFS) and overall survival (OS). A predictive scoring system using American Joint Committee on Cancer (AJCC) pathological staging and immunological markers was created. Association of high CD8 and low FOXP3 cell infiltrates after chemotherapy was significantly associated with improved RFS (p = 0.02) and OS (p = 0.002), and outperformed classical predictive factors in multivariate analysis. A combined score associating CD8/FOXP3 ratio and pathological AJCC staging isolated a subgroup of patients with a long-term overall survival of 100%. Importantly, this score also identified patients with a favourable prognosis in an independent cohort of HER2-negative breast cancer patients. These results suggest that immunological CD8 and FOXP3 cell infiltrate after treatment is an independent predictive factor of survival in breast cancer patients treated with neoadjuvant chemotherapy and provides new insights into the role of the immune milieu and cancer. Copyright © 2011 Pathological Society of Great Britain and Ireland. Published by John Wiley & Sons, Ltd.

  6. Imaging in unilateral Wilms tumour

    International Nuclear Information System (INIS)

    Brisse, Herve J.; Smets, Anne M.; Kaste, Sue C.; Owens, Catherine M.

    2008-01-01

    Wilms tumour is one of the most common malignancies in children, with an excellent prognosis after therapy. There is a very diverse approach to treatment according to geographical location. This variation in therapeutic attitude toward Wilms tumour, particularly between the United States and Europe, has consequences for the choice of imaging modality at diagnosis. In Europe, the International Society of Paediatric Oncology (SIOP) treatment protocol is based on chemotherapy followed by surgery. Imaging (US, CT and MRI), clinical history and examination will help predict whether the findings are consistent with Wilms tumour. Furthermore, in the UK preoperative image-guided biopsy is advised to help identify the small group of patients who, despite typical imaging features of Wilms tumour, have other types of neoplasia that require alternative management. In the United States, the National Wilms Tumor Study (NWTS) advises surgery prior to chemo- and radiotherapy. Hence imaging must provide detailed anatomical information for surgical planning. This article discusses the role of imaging at diagnosis and the relative strengths and weaknesses of the available radiological techniques. We also focus on imaging the lung for metastatic disease and the consequences (to the patient's ultimate outcome) of CT-diagnosed small pulmonary nodules and discuss the radiological diagnosis and consequences of tumour rupture present at diagnosis. (orig.)

  7. Lifestyle influences on the association between pre-diagnostic hormone replacement therapy and breast cancer prognosis - results from The Danish 'Diet, Cancer and Health' prospective cohort

    DEFF Research Database (Denmark)

    Holm, Marianne; Olsen, Anja; Kroman, Niels

    2014-01-01

    OBJECTIVES: The association between pre-diagnostic hormone replacement therapy (HRT) and breast cancer specific mortality as well as potential influences from other lifestyle factors on the association was investigated. STUDY DESIGN: Female participants from the prospective cohort "Diet, Cancer......, and Health" diagnosed with breast cancer (BC) were identified and their pre-diagnostic HRT use evaluated for association with tumour biology and breast cancer outcome in multivariate analysis. MAIN OUTCOME MEASURE: Breast cancer specific mortality. RESULTS: Of the 1212 patients originally considered 1064...... were included. Of these, 105 women died from breast cancer during a median follow-up of 6.3 years (range 0.2-14.3 years). In multivariate analyses women who used HRT at enrolment into the cohort study had 47% lower risk of dying from breast cancer as compared to women who had previously or never used...

  8. Factors influencing late stage of breast cancer at presentation in a district Hospital - Segamat Hospital, Johor.

    Science.gov (United States)

    Cheng, M L; Ling, D Y; Nanu P, K P; Nording, H; Lim, C H

    2015-06-01

    In Malaysia, late stage presentation of breast cancer (stage III or IV) has been a healthcare problem that varies geographically throughout the country. This study aims to understand the factors influencing late stage of breast cancer at presentation among Malaysian women in Segamat Hospital, Johor, which is a district hospital. A retrospective descriptive study was conducted on secondary data of all newly diagnosed breast cancer women from 1st August 2011 to 28th February 2014. Secondary data includes age, ethnicity, marital status, family history, education level, occupation, presenting symptom, duration of symptom, tumour size, tumour pathology, tumour grading, oestrogen, progesterone and HER-2 receptor status were collected and analysed using SPSS version 20.0.0. In total, data from 52 women was analysed and two women were excluded for incompleteness as these women defaulted. Late stage at presentation was 59.6% of all new cases (17.3% stage III and 42.3% stage IV). The commonest age group of all women diagnosed with breast cancer was in the 5th decade. Majority of them were Malay, married and housewives with no family history of breast cancer. The statistically significant factors associated with late stage at presentation include Malay ethnicity (p=0.019), presenting symptoms other than breast lump (p=0.047), and duration of breast lump more than 3 months (p=0.009). The study demonstrated presentation at late stage of breast cancer is a major health concern among Malaysian women in district hospital. This may be attributed to different sociocultural beliefs, strong belief in complementary and alternative medicine, lack of awareness, and difficult accessibility to healthcare services.

  9. Urokinase plasminogen activator (uPA and plasminogen activator inhibitor type-1 (PAI-1 in breast cancer - correlation with traditional prognostic factors

    Directory of Open Access Journals (Sweden)

    Lampelj Maja

    2015-12-01

    Full Text Available Background. Urokinase plasminogen activator (uPA and plasminogen activator inhibitor type-1 (PAI-1 play a key role in tumour invasion and metastasis. High levels of both proteolytic enzymes are associated with poor prognosis in breast cancer patients. The purpose of this study was to evaluate the correlation between traditional prognostic factors and uPA and PAI-1 expression in primary tumour of breast cancer patients.

  10. Iodide transport and breast cancer.

    Science.gov (United States)

    Poole, Vikki L; McCabe, Christopher J

    2015-10-01

    Breast cancer is the second most common cancer worldwide and the leading cause of cancer death in women, with incidence rates that continue to rise. The heterogeneity of the disease makes breast cancer exceptionally difficult to treat, particularly for those patients with triple-negative disease. To address the therapeutic complexity of these tumours, new strategies for diagnosis and treatment are urgently required. The ability of lactating and malignant breast cells to uptake and transport iodide has led to the hypothesis that radioiodide therapy could be a potentially viable treatment for many breast cancer patients. Understanding how iodide is transported, and the factors regulating the expression and function of the proteins responsible for iodide transport, is critical for translating this hypothesis into reality. This review covers the three known iodide transporters - the sodium iodide symporter, pendrin and the sodium-coupled monocarboxylate transporter - and their role in iodide transport in breast cells, along with efforts to manipulate them to increase the potential for radioiodide therapy as a treatment for breast cancer. © 2015 Society for Endocrinology.

  11. High-resolution analysis of 16q22.1 in breast carcinoma using DNA amplifiable probes (multiplex amplifiable probe hybridization technique) and immunohistochemistry.

    Science.gov (United States)

    Rakha, Emad A; Armour, John A L; Pinder, Sarah E; Paish, Claire E; Ellis, Ian O

    2005-05-01

    Loss of the chromosomal material at 16q22.1 is one of the most frequent genetic aberrations found in both lobular and low-grade nonlobular invasive carcinoma of the breast, indicating the presence of a tumour suppressor gene (TSG) at this region in these tumours. However, the TSG (s) at the 16q22.1 in the more frequent nonlobular carcinomas is still unknown. Multiplex Amplifiable Probe Hybridisation (MAPH) is a simple, accurate and a high-resolution technique that provides an alternative approach to DNA copy-number measurement. The aim of our study was to examine the most likely candidate genes at 16q22.1 using MAPH assay combined with protein expression analysis by immunohistochemistry. We identified deletion at 16q22.1 that involves some or all of these genes. We also noticed that the smallest region of deletion at 16q22.1 could be delineated to a 3 Mb region centromeric to the P-cadherin gene. Apart from the correlation between E-cadherin protein expression and its gene copy number, no correlation was detected between the expression of E2F-4, CTCF, TRF2 or P-cadherin with their gene's copy number. In the malignant tissues, no significant loss or decrease of protein expression of any gene other than E-cadherin was seen in association with any specific tumour type. No expression of VE-cadherin or Ksp-cadherin was detected in the normal and/or malignant tissues of the breast in these cases. However, there was a correlation between increased nuclear expression of E2F-4 and tumours with higher histological grade (p = 0.04) and positive lymph node disease (p = 0.02), suggesting that it may have an oncogenic rather than a tumour suppressor role. The malignant breast tissues also showed abnormal cytoplasmic cellular localisation of CTCF, compared to its expression in the normal parenchymal cells. In conclusion, we have demonstrated that MAPH is a potential technique for assessment of genomic imbalances in malignant tissues. Although our results support E-cadherin as the

  12. Intake of whole grain products and risk of breast cancer by hormone receptor status and histology among postmenopausal women

    DEFF Research Database (Denmark)

    Egeberg, Rikke; Olsen, Anja; Loft, Steffen

    2009-01-01

    No clear relationship between whole grain products and risk of breast cancer has been established. In a large prospective cohort study, we investigated the association between intake of whole grain products and risk of breast cancer by tumour receptor status [oestrogen receptor (ER......) and progesterone receptor (PR)] and tumour histology (ductal/lobular). It was further investigated whether the association differed by use of hormone replacement therapy (HRT). The study included 25,278 postmenopausal women participating in the Danish Diet, Cancer and Health cohort study (1993-1997). During a mean...... follow-up time of 9.6 years, 978 breast cancer cases were diagnosed. Associations between intake of whole grain products and the breast cancer rate were analysed using Cox's regression model. A higher intake of whole grain products was not associated with a lower risk of breast cancer. Per an increment...

  13. Target volume definition for external beam partial breast radiotherapy: Clinical, pathological and technical studies informing current approaches

    International Nuclear Information System (INIS)

    Kirby, Anna M.; Coles, Charlotte E.; Yarnold, John R.

    2010-01-01

    Partial breast irradiation (PBI) is currently under investigation in several phase III trials and, following a recent consensus statement, its use off-study may increase despite ongoing uncertainty regarding optimal target volume definition. We review the clinical, pathological and technical evidence for target volume definition in external beam partial breast irradiation (EB-PBI). The optimal method of tumour bed (TB) delineation requires X-ray CT imaging of implanted excision cavity wall markers. The definition of clinical target volume (CTV) as TB plus concentric 15 mm margins is based on the anatomical distribution of multifocal and multicentric disease around the primary tumour in mastectomy specimens, and the clinical locations of local tumour relapse (LR) after breast conservation surgery. If the majority of LR originate from foci of residual invasive and/or intraduct disease in the vicinity of the TB after complete microscopic resection, CTV margin logically takes account of the position of primary tumour within the surgical resection specimen. The uncertain significance of independent primary tumours as sources of preventable LR, and of wound healing responses in stimulating LR, increases the difficulties in defining optimal CTV. These uncertainties may resolve after long-term follow-up of current PBI trials. By contrast, a commonly used 10 mm clinical to planning target volume (PTV) margin has a stronger evidence base, although departmental set-up errors need to be confirmed locally. A CTV-PTV margin >10 mm may be required in women with larger breasts and/or large seromas, whilst the role of image-guided radiotherapy with or without TB markers in reducing CTV-PTV margins needs to be explored.

  14. Computer-aided interpretation of dynamic magnetic resonance imaging reflects histopathology of invasive breast cancer

    International Nuclear Information System (INIS)

    Baltzer, Pascal A.T.; Vag, Tibor; Dietzel, Matthias; Beger, Sebastian; Freiberg, Christian; Kaiser, Werner A.; Gajda, Mieczyslaw; Camara, Oumar

    2010-01-01

    To perform a semiautomated software-based comparison of invasive breast carcinoma dynamic enhancement patterns in MR mammography with histological prognostic factors considering whole lesion volumes. A total of 128 patients with 145 invasive breast carcinomas underwent dynamic MR mammography. Kinetic features from the invasive breast lesions were obtained using commercially available software to automatically assess volume enhancement characteristics of a manually chosen lesion. Findings were compared with histological factors determining tumour aggressiveness (lymph node status, LN; oestrogen/progesterone receptor (ER/PR) status; HER-2/neu status; tumour grade) by using nonparametric rank tests and binary logistic regression analysis (BLRA). Volume enhancement characteristics were significantly influenced by LN, ER/PR and HER-2/neu status (P<0.05). BLRA implied that total lesion and plateau voxel volume were independent predictors of ER/PR and HER-2/neu status. Strongest initial enhancement predicted negative ER/PR, and time to peak of the most suspect curve was inversely correlated with positive LN status. On the other hand, no statistical significance could be observed between histological tumour grading and kinetic features. Histopathological criteria associated with poor prognosis lead to significantly more aggressive dynamic enhancement patterns in MR mammography. In this study, higher lesion volumes as well as higher and earlier initial enhancement were independent covariates predicting higher tumour aggressiveness. (orig.)

  15. The Succinated Proteome of FH-Mutant Tumours

    Directory of Open Access Journals (Sweden)

    Ming Yang

    2014-08-01

    Full Text Available Inherited mutations in the Krebs cycle enzyme fumarate hydratase (FH predispose to hereditary leiomyomatosis and renal cell cancer (HLRCC. Loss of FH activity in HLRCC tumours causes accumulation of the Krebs cycle intermediate fumarate to high levels, which may act as an oncometabolite through various, but not necessarily mutually exclusive, mechanisms. One such mechanism, succination, is an irreversible non-enzymatic modification of cysteine residues by fumarate, to form S-(2-succinocysteine (2SC. Previous studies have demonstrated that succination of proteins including glyceraldehyde 3-phosphate dehydrogenase (GAPDH, kelch-like ECH-associated protein 1 (KEAP1 and mitochondrial aconitase (ACO2 can have profound effects on cellular metabolism. Furthermore, immunostaining for 2SC is a sensitive and specific biomarker for HLRCC tumours. Here, we performed a proteomic screen on an FH-mutant tumour and two HLRCC-derived cancer cell lines and identified 60 proteins where one or more cysteine residues were succinated; 10 of which were succinated at cysteine residues either predicted, or experimentally proven, to be functionally significant. Bioinformatic enrichment analyses identified most succinated targets to be involved in redox signaling. To our knowledge, this is the first proteomic-based succination screen performed in human tumours and cancer-derived cells and has identified novel 2SC targets that may be relevant to the pathogenesis of HLRCC.

  16. Changing pattern of malignancies: analysis of histopathology based tumour registry data and comparison of three decades at armed forces institute of pathology rawalpindi, Pakistan

    International Nuclear Information System (INIS)

    Jamal, S.

    2014-01-01

    Objective: To assess the pattern of malignancies from tumour registry data and to find any changing pattern by comparing corresponding data from earlier periods. Methods: The descriptive study was carried out at the Department of Histopathology, Armed Forces Institute of Pathology (AFIP), Rawalpindi, Pakistan. All malignant tumours from 2002-2011 were analysed for age groups, gender distribution, and type of tumour with relation to the site. Tumours of paediatric age group were also assessed separately. Comparison with national and international studies and the data of previous decades - 1977-1988 and 1992-2001 was done to find any changing pattern. SPSS 15 was used for statistical analysis. Results: A total of 32718 malignant tumours were analysed. Of them, males were 19191 and 13527 were females (M:F ratio: 1.4:1). Majority of the patients were between 50-70 years of age. In males, urinary bladder tumours 2153 (11.2%), followed by combined lymphoma/leukaemia 2020 (10.5%) and prostate 1825 (9.5%) were top three malignancies, whereas in females breast 4178 (30.9%) was the commonest. Comparison of different decades showed that in males in the first monograph lymphoma was the commonest, then it was prostatic carcinoma in the second monograph, and now tumours of urinary bladder were on top position. In females, carcinoma cervix, which was at number 5 and 9 in the two earlier monographs was not found in the list of current 10 common tumours. Conclusion: The study showed some interesting features, particularly in male malignancies and those related to urinary bladder tumours. The persistent increasing frequency of breast carcinoma in females is also alarming, and requires extensive efforts of awareness, screening and early detection programmes. (author)

  17. A difficult decision: what should we do when malignant tumours are diagnosed in patients supported by left ventricular assist devices?

    Science.gov (United States)

    Smail, Hassiba; Pfister, Christian; Baste, Jean-Marc; Nafeh-Bizet, Catherine; Gay, Arnaud; Barbay, Virginie; Bessou, Jean-Paul; Peillon, Christophe; Litzler, Pierre-Yves

    2015-09-01

    Left ventricular assist devices (LVADs) are used as a bridge to heart transplantation. During the preimplantation or pretransplantation screening, malignant tumours can be discovered. Owing to the lack of guidelines, the management is difficult. We describe our perioperative approach and the patients' outcomes. Between 2006 and 2014, 55 patients underwent implantation of HeartMate II LVAD. Five were diagnosed with malignant tumours: 2 renal, 2 lung and 1 breast tumours. The renal tumours were diagnosed during the preimplantation screening. An LVAD was implanted in both followed by partial nephrectomies 8 and 9 months later. The lung cancers were diagnosed after device implantation, a left pulmonary segmentectomy and a right upper sleeve lobectomy were performed. The breast cancer was diagnosed few months after support and a tumourectomy with lymphadenectomy was performed. Tumour resection was performed successfully in all patients. Prior to surgery haemostasis, device and heart function were evaluated. During surgery, haemodynamics and anticoagulation were monitored. Reoperations were necessary to evacuate haemothorax after lobectomy and an abdominal haematoma post-nephrectomy. After discussion with oncologists, 3 patients were relisted for heart transplantation. Two were successfully transplanted 2 and 3 years after partial nephrectomy with an actual survival of 56 and 59 months after the cancer diagnosis. The follow-up revealed no cancer recurrences. Malignant tumours during support with LVAD can be successfully resected. A multidisciplinary evaluation in these high-risk patients is mandatory. After careful evaluation, regaining the patient's heart transplant candidacy is possible. © The Author 2015. Published by Oxford University Press on behalf of the European Association for Cardio-Thoracic Surgery. All rights reserved.

  18. The immunomodulator PSK induces in vitro cytotoxic activity in tumour cell lines via arrest of cell cycle and induction of apoptosis

    Directory of Open Access Journals (Sweden)

    Garrido Federico

    2008-03-01

    Full Text Available Abstract Background Protein-bound polysaccharide (PSK is derived from the CM-101 strain of the fungus Coriolus versicolor and has shown anticancer activity in vitro and in in vivo experimental models and human cancers. Several randomized clinical trials have demonstrated that PSK has great potential in adjuvant cancer therapy, with positive results in the adjuvant treatment of gastric, esophageal, colorectal, breast and lung cancers. These studies have suggested the efficacy of PSK as an immunomodulator of biological responses. The precise molecular mechanisms responsible for its biological activity have yet to be fully elucidated. Methods The in vitro cytotoxic anti-tumour activity of PSK has been evaluated in various tumour cell lines derived from leukaemias, melanomas, fibrosarcomas and cervix, lung, pancreas and gastric cancers. Tumour cell proliferation in vitro was measured by BrdU incorporation and viable cell count. Effect of PSK on human peripheral blood lymphocyte (PBL proliferation in vitro was also analyzed. Studies of cell cycle and apoptosis were performed in PSK-treated cells. Results PSK showed in vitro inhibition of tumour cell proliferation as measured by BrdU incorporation and viable cell count. The inhibition ranged from 22 to 84%. Inhibition mechanisms were identified as cell cycle arrest, with cell accumulation in G0/G1 phase and increase in apoptosis and caspase-3 expression. These results indicate that PSK has a direct cytotoxic activity in vitro, inhibiting tumour cell proliferation. In contrast, PSK shows a synergistic effect with IL-2 that increases PBL proliferation. Conclusion These results indicate that PSK has cytotoxic activity in vitro on tumour cell lines. This new cytotoxic activity of PSK on tumour cells is independent of its previously described immunomodulatory activity on NK cells.

  19. The prognostic value of oncogenic antigen 519 (OA-519) expression and proliferative activity detected by antibody MIB-1 in node-negative breast cancer

    DEFF Research Database (Denmark)

    Jensen, V; Ladekarl, M; Holm-Nielsen, P

    1995-01-01

    The prognostic value of oncogenic antigen 519 (OA-519) expression and tumour proliferative activity was evaluated in a retrospective series of 118 patients with low-risk breast cancer. Low risk was defined as negative axillary nodes, tumour diameter histological evidence...... analysis, both the MIB-1 index and OA-519 expression were of independent prognostic value (2p breast cancer who might benefit from adjuvant therapy....

  20. Investigation of gene-environment interactions between 47 newly identified breast cancer susceptibility loci and environmental risk factors

    NARCIS (Netherlands)

    Rudolph, Anja; Milne, Roger L.; Truong, Thérèse; Knight, Julia A.; Seibold, Petra; Flesch-Janys, Dieter; Behrens, Sabine; Eilber, Ursula; Bolla, Manjeet K.; Wang, Qin; Dennis, Joe; Dunning, Alison M.; Shah, Mitul; Munday, Hannah R.; Darabi, Hatef; Eriksson, Mikael; Brand, Judith S.; Olson, Janet; Vachon, Celine M.; Hallberg, Emily; Castelao, J. Esteban; Carracedo, Angel; Torres, Maria; Li, Jingmei; Humphreys, Keith; Cordina-Duverger, Emilie; Menegaux, Florence; Flyger, Henrik; Nordestgaard, Børge G.; Nielsen, Sune F.; Yesilyurt, Betul T.; Floris, Giuseppe; Leunen, Karin; Engelhardt, Ellen G.; Broeks, Annegien; Rutgers, Emiel J.; Glendon, Gord; Mulligan, Anna Marie; Cross, Simon; Reed, Malcolm; Gonzalez-Neira, Anna; Arias Perez, José Ignacio; Provenzano, Elena; Apicella, Carmel; Southey, Melissa C.; Spurdle, Amanda; Häberle, Lothar; Beckmann, Matthias W.; Ekici, Arif B.; Dieffenbach, Aida Karina; Arndt, Volker; Stegmaier, Christa; McLean, Catriona; Baglietto, Laura; Chanock, Stephen J.; Lissowska, Jolanta; Sherman, Mark E.; Brüning, Thomas; Hamann, Ute; Ko, Yon-Dschun; Orr, Nick; Schoemaker, Minouk; Ashworth, Alan; Kosma, Veli-Matti; Kataja, Vesa; Hartikainen, Jaana M.; Mannermaa, Arto; Swerdlow, Anthony; Giles, Graham G.; Brenner, Hermann; Fasching, Peter A.; Chenevix-Trench, Georgia; Hopper, John; Benítez, Javier; Cox, Angela; Andrulis, Irene L.; Lambrechts, Diether; Gago-Dominguez, Manuela; Couch, Fergus; Czene, Kamila; Bojesen, Stig E.; Easton, Doug F.; Schmidt, Marjanka K.; Guénel, Pascal; Hall, Per; Pharoah, Paul D. P.; Garcia-Closas, Montserrat; Chang-Claude, Jenny

    2015-01-01

    A large genotyping project within the Breast Cancer Association Consortium (BCAC) recently identified 41 associations between single nucleotide polymorphisms (SNPs) and overall breast cancer (BC) risk. We investigated whether the effects of these 41 SNPs, as well as six SNPs associated with estrogen

  1. [Day surgery in breast reconstructive surgery: our experience].

    Science.gov (United States)

    Fierro, N; D'Ermo, G; Barbetti, E; Mazza, E; Gallinaro, L S; Amanti, C; De Biasio, G; Galassi, G; Galassi, G

    2004-10-01

    Breast cancer is the most common tumour in Italy in the female population, counting for about 40000 new cases every year. The psychological aspects of breast mutilation and the social and economic implications are receiving increasing attention. Despite of the diffusion of screening programs to detect pre-clinical breast cancers, 30% of patients still undergo radical interventions. Therefore, many women present serious limitations of their social-life that can lead to severe depression since, in occidental countries, the biological function of the breast is less considered than its primary role of femininity and sexuality. The gold-standard is to conceal oncological radicality and aesthetic preservation. The Authors present their experience analysing the techniques employed.

  2. Malignant eccrine breast spiradenoma. A case report and literature review

    Directory of Open Access Journals (Sweden)

    Alejandra de Andrés Gómez

    2015-01-01

    Conclusion: Eccrine spiradenomas are rare adnexal tumours of the skin. Intraparenquimatous breast location is especially infrequent. Diagnosis is based on histopathological examination. MES metastasizes (40%, so a close follow up is recommended.

  3. Association analysis identifies 65 new breast cancer risk loci

    NARCIS (Netherlands)

    Michailidou, Kyriaki; Lindström, Sara; Dennis, Joe; Beesley, Jonathan; Hui, Shirley; Kar, Siddhartha; Lemaçon, Audrey; Soucy, Penny; Glubb, Dylan; Rostamianfar, Asha; Bolla, Manjeet K.; Wang, Qin; Tyrer, Jonathan; Dicks, Ed; Lee, Andrew; Wang, Zhaoming; Allen, Jamie; Keeman, Renske; Eilber, Ursula; French, Juliet D.; Qing Chen, Xiao; Fachal, Laura; McCue, Karen; McCart Reed, Amy E.; Ghoussaini, Maya; Carroll, Jason S.; Jiang, Xia; Finucane, Hilary; Adams, Marcia; Adank, Muriel A.; Ahsan, Habibul; Aittomäki, Kristiina; Anton-Culver, Hoda; Antonenkova, Natalia N.; Arndt, Volker; Aronson, Kristan J.; Arun, Banu; Auer, Paul L.; Bacot, François; Barrdahl, Myrto; Baynes, Caroline; Beckmann, Matthias W.; Behrens, Sabine; Benitez, Javier; Bermisheva, Marina; Bernstein, Leslie; Blomqvist, Carl; Bogdanova, Natalia V.; Bojesen, Stig E.; Bonanni, Bernardo; Børresen-Dale, Anne-Lise; Brand, Judith S.; Brauch, Hiltrud; Brennan, Paul; Brenner, Hermann; Brinton, Louise; Broberg, Per; Brock, Ian W.; Broeks, Annegien; Brooks-Wilson, Angela; Brucker, Sara Y.; Brüning, Thomas; Burwinkel, Barbara; Butterbach, Katja; Cai, Qiuyin; Cai, Hui; Caldés, Trinidad; Canzian, Federico; Carracedo, Angel; Carter, Brian D.; Castelao, Jose E.; Chan, Tsun L.; David Cheng, Ting-Yuan; Seng Chia, Kee; Choi, Ji-Yeob; Christiansen, Hans; Clarke, Christine L.; Collée, Margriet; Conroy, Don M.; Cordina-Duverger, Emilie; Cornelissen, Sten; Cox, David G.; Cox, Angela; Cross, Simon S.; Cunningham, Julie M.; Czene, Kamila; Daly, Mary B.; Devilee, Peter; Doheny, Kimberly F.; Dörk, Thilo; Dos-Santos-Silva, Isabel; Dumont, Martine; Durcan, Lorraine; Dwek, Miriam; Eccles, Diana M.; Ekici, Arif B.; Eliassen, A. Heather; Ellberg, Carolina; Elvira, Mingajeva; Engel, Christoph; Eriksson, Mikael; Fasching, Peter A.; Figueroa, Jonine; Flesch-Janys, Dieter; Fletcher, Olivia; Flyger, Henrik; Fritschi, Lin; Gaborieau, Valerie; Gabrielson, Marike; Gago-Dominguez, Manuela; Gao, Yu-Tang; Gapstur, Susan M.; García-Sáenz, José A.; Gaudet, Mia M.; Georgoulias, Vassilios; Giles, Graham G.; Glendon, Gord; Goldberg, Mark S.; Goldgar, David E.; González-Neira, Anna; Grenaker Alnæs, Grethe I.; Grip, Mervi; Gronwald, Jacek; Grundy, Anne; Guénel, Pascal; Haeberle, Lothar; Hahnen, Eric; Haiman, Christopher A.; Håkansson, Niclas; Hamann, Ute; Hamel, Nathalie; Hankinson, Susan; Harrington, Patricia; Hart, Steven N.; Hartikainen, Jaana M.; Hartman, Mikael; Hein, Alexander; Heyworth, Jane; Hicks, Belynda; Hillemanns, Peter; Ho, Dona N.; Hollestelle, Antoinette; Hooning, Maartje J.; Hoover, Robert N.; Hopper, John L.; Hou, Ming-Feng; Hsiung, Chia-Ni; Huang, Guanmengqian; Humphreys, Keith; Ishiguro, Junko; Ito, Hidemi; Iwasaki, Motoki; Iwata, Hiroji; Jakubowska, Anna; Janni, Wolfgang; John, Esther M.; Johnson, Nichola; Jones, Kristine; Jones, Michael; Jukkola-Vuorinen, Arja; Kaaks, Rudolf; Kabisch, Maria; Kaczmarek, Katarzyna; Kang, Daehee; Kasuga, Yoshio; Kerin, Michael J.; Khan, Sofia; Khusnutdinova, Elza; Kiiski, Johanna I.; Kim, Sung-Won; Knight, Julia A.; Kosma, Veli-Matti; Kristensen, Vessela N.; Krüger, Ute; Kwong, Ava; Lambrechts, Diether; Le Marchand, Loic; Lee, Eunjung; Lee, Min Hyuk; Lee, Jong Won; Neng Lee, Chuen; Lejbkowicz, Flavio; Li, Jingmei; Lilyquist, Jenna; Lindblom, Annika; Lissowska, Jolanta; Lo, Wing-Yee; Loibl, Sibylle; Long, Jirong; Lophatananon, Artitaya; Lubinski, Jan; Luccarini, Craig; Lux, Michael P.; Ma, Edmond S. K.; MacInnis, Robert J.; Maishman, Tom; Makalic, Enes; Malone, Kathleen E.; Kostovska, Ivana Maleva; Mannermaa, Arto; Manoukian, Siranoush; Manson, JoAnn E.; Margolin, Sara; Mariapun, Shivaani; Martinez, Maria Elena; Matsuo, Keitaro; Mavroudis, Dimitrios; McKay, James; McLean, Catriona; Meijers-Heijboer, Hanne; Meindl, Alfons; Menéndez, Primitiva; Menon, Usha; Meyer, Jeffery; Miao, Hui; Miller, Nicola; Taib, Nur Aishah Mohd; Muir, Kenneth; Mulligan, Anna Marie; Mulot, Claire; Neuhausen, Susan L.; Nevanlinna, Heli; Neven, Patrick; Nielsen, Sune F.; Noh, Dong-Young; Nordestgaard, Børge G.; Norman, Aaron; Olopade, Olufunmilayo I.; Olson, Janet E.; Olsson, Håkan; Olswold, Curtis; Orr, Nick; Pankratz, V. Shane; Park, Sue K.; Park-Simon, Tjoung-Won; Lloyd, Rachel; Perez, Jose I. A.; Peterlongo, Paolo; Peto, Julian; Phillips, Kelly-Anne; Pinchev, Mila; Plaseska-Karanfilska, Dijana; Prentice, Ross; Presneau, Nadege; Prokofyeva, Darya; Pugh, Elizabeth; Pylkäs, Katri; Rack, Brigitte; Radice, Paolo; Rahman, Nazneen; Rennert, Gadi; Rennert, Hedy S.; Rhenius, Valerie; Romero, Atocha; Romm, Jane; Ruddy, Kathryn J.; Rüdiger, Thomas; Rudolph, Anja; Ruebner, Matthias; Rutgers, Emiel J. T.; Saloustros, Emmanouil; Sandler, Dale P.; Sangrajrang, Suleeporn; Sawyer, Elinor J.; Schmidt, Daniel F.; Schmutzler, Rita K.; Schneeweiss, Andreas; Schoemaker, Minouk J.; Schumacher, Fredrick; Schürmann, Peter; Scott, Rodney J.; Scott, Christopher; Seal, Sheila; Seynaeve, Caroline; Shah, Mitul; Sharma, Priyanka; Shen, Chen-Yang; Sheng, Grace; Sherman, Mark E.; Shrubsole, Martha J.; Shu, Xiao-Ou; Smeets, Ann; Sohn, Christof; Southey, Melissa C.; Spinelli, John J.; Stegmaier, Christa; Stewart-Brown, Sarah; Stone, Jennifer; Stram, Daniel O.; Surowy, Harald; Swerdlow, Anthony; Tamimi, Rulla; Taylor, Jack A.; Tengström, Maria; teo, Soo H.; Beth Terry, Mary; Tessier, Daniel C.; Thanasitthichai, Somchai; Thöne, Kathrin; Tollenaar, Rob A. E. M.; Tomlinson, Ian; Tong, Ling; Torres, Diana; Truong, Thérèse; Tseng, Chiu-Chen; Tsugane, Shoichiro; Ulmer, Hans-Ulrich; Ursin, Giske; Untch, Michael; Vachon, Celine; van Asperen, Christi J.; van den Berg, David; van den Ouweland, Ans M. W.; van der Kolk, Lizet; van der Luijt, Rob B.; Vincent, Daniel; Vollenweider, Jason; Waisfisz, Quinten; Wang-Gohrke, Shan; Weinberg, Clarice R.; Wendt, Camilla; Whittemore, Alice S.; Wildiers, Hans; Willett, Walter; Winqvist, Robert; Wolk, Alicja; Wu, Anna H.; Xia, Lucy; Yamaji, Taiki; Yang, Xiaohong R.; Har Yip, Cheng; Yoo, Keun-Young; Yu, Jyh-Cherng; Zheng, Wei; Zheng, Ying; Zhu, Bin; Ziogas, Argyrios; Ziv, Elad; Lakhani, Sunil R.; Antoniou, Antonis C.; Droit, Arnaud; Andrulis, Irene L.; Amos, Christopher I.; Couch, Fergus J.; Pharoah, Paul D. P.; Chang-Claude, Jenny; Hall, Per; Hunter, David J.; Milne, Roger L.; García-Closas, Montserrat; Schmidt, Marjanka K.; Chanock, Stephen J.; Dunning, Alison M.; Edwards, Stacey L.; Bader, Gary D.; Chenevix-Trench, Georgia; Simard, Jacques; Kraft, Peter; Easton, Douglas F.

    2017-01-01

    Breast cancer risk is influenced by rare coding variants in susceptibility genes, such as BRCA1, and many common, mostly non-coding variants. However, much of the genetic contribution to breast cancer risk remains unknown. Here we report the results of a genome-wide association study of breast

  4. Does shear wave ultrasound independently predict axillary lymph node metastasis in women with invasive breast cancer?

    Science.gov (United States)

    Evans, Andrew; Rauchhaus, Petra; Whelehan, Patsy; Thomson, Kim; Purdie, Colin A; Jordan, Lee B; Michie, Caroline O; Thompson, Alastair; Vinnicombe, Sarah

    2014-01-01

    Shear wave elastography (SWE) shows promise as an adjunct to greyscale ultrasound examination in assessing breast masses. In breast cancer, higher lesion stiffness on SWE has been shown to be associated with features of poor prognosis. The purpose of this study was to assess whether lesion stiffness at SWE is an independent predictor of lymph node involvement. Patients with invasive breast cancer treated by primary surgery, who had undergone SWE examination were eligible. Data were retrospectively analysed from 396 consecutive patients. The mean stiffness values were obtained using the Aixplorer® ultrasound machine from SuperSonic Imagine Ltd. Measurements were taken from a region of interest positioned over the stiffest part of the abnormality. The average of the mean stiffness value obtained from each of two orthogonal image planes was used for analysis. Associations between lymph node involvement and mean lesion stiffness, invasive cancer size, histologic grade, tumour type, ER expression, HER-2 status and vascular invasion were assessed using univariate and multivariate logistic regression. At univariate analysis, invasive size, histologic grade, HER-2 status, vascular invasion, tumour type and mean stiffness were significantly associated with nodal involvement. Nodal involvement rates ranged from 7 % for tumours with mean stiffness 150 kPa. At multivariate analysis, invasive size, tumour type, vascular invasion, and mean stiffness maintained independent significance. Mean stiffness at SWE is an independent predictor of lymph node metastasis and thus can confer prognostic information additional to that provided by conventional preoperative tumour assessment and staging.

  5. Typing and grading of cytological category C5 breast lesions

    International Nuclear Information System (INIS)

    Zafar, N.; Jamal, S.; Mamoon, N.; Luqman, M.; Anwar, M.

    2005-01-01

    Objective: To determine the tumour type, cytological grade and nuclear grade on fine-needle aspiration smears in cytological category C5 breast lesions and compare them with histopathological findings. Subjects and Methods: Out of all patients referred to AFIP, Rawalpindi for fine-needle aspiration of breast masses, those adjudged C5 (malignant) were chosen for this study. History, clinical details and mammographic findings were noted. Aspirated smears were examined and an attempt was made to ascertain tumour type, cytological grade and nuclear grade. On excision of these lesions, the cytological findings were compared with those on paraffin-embedded histological sections. Results: A total of 71 patients were included in this study. Of these, 64 (90.14%) were cytologically diagnosed as ductal carcinoma, 4 (5.63%) lobular carcinoma, 2 (2.82%) mucinous carcinoma and 1 (1.41%) as medullary carcinoma. Seventy (98.60%) tumours were correctly typed on aspiration smears. Sixty-eight (95.77%) cases were cytologically graded with accuracy. Nuclear grading was even better on cytology and, excluding one malignant lymphoma, all 70 (100%) smears were assessed correctly. Conclusion: Overall efficiency of the tumour typing, cytological grading and nuclear grading on aspirated material turned out to be quite accurate. In expert hands, cytological examination can be of great help in pre-operative planning and in cases where tumour morphology in paraffin-embedded material has been distorted by neo-adjuvant therapy prior to excision. (author)

  6. Mystery of bilateral breast masses

    Directory of Open Access Journals (Sweden)

    Nausheen Khan

    2011-12-01

    Full Text Available Leiomyosarcoma (LMS is an uncommon malignant tumour of smooth muscle origin. It arises in the gastro intestinal tract, retroperitoneum, urinary bladder, uterus and soft tissue. Peritoneal leiomyosarcomatosis (PL is defined as a peritoneal dissemination of a primary sarcoma. We present a case of leiomyosarcomatosis with wide spread dissemination including involvement of both breasts.

  7. Recent childbirth is an adverse prognostic factor in breast cancer and melanoma, but not in Hodgkin lymphoma.

    Science.gov (United States)

    Møller, Henrik; Purushotham, Arnie; Linklater, Karen M; Garmo, Hans; Holmberg, Lars; Lambe, Mats; Yallop, Deborah; Devereux, Stephen

    2013-11-01

    The relationship between gestation, childbirth and cancer prognosis is unknown for most cancers (e.g. Hodgkin lymphoma), whereas a body of evidence exists for melanoma and breast cancer. The national cancer registration and hospital discharge data for women in England (1998-2007) were linked, and the records for Hodgkin lymphoma, melanoma and breast cancer were indexed as to whether women had delivered a child in separate time periods prior to their cancer diagnosis. Survival analyses were conducted in order to characterise prognosis in relation to childbirth, with statistical adjustment for age and (where possible) stage. For melanoma and breast cancer, survival was strongly reduced in women who gave birth in the year prior to cancer diagnosis. The age-adjusted hazard ratios (HR) with 95% confidence intervals (CI) were 2.06 (1.42-3.01) for melanoma and 1.84 (1.64-2.06) for breast cancer. The associations were only slightly attenuated by further adjustment for tumour stage. For breast cancer, the excess death rate in women with a recent childbirth peaked at 2 years and remained elevated for 6 to 8 years. Previous childbirth had no overall effect on the outcome of Hodgkin lymphoma. Melanoma and breast cancer prognosis are adversely affected by recent gestation and childbirth in a way that is not due to stage of the cancer, but rather to inherent biological properties of the tumours. Possible biological mechanisms include immunosuppression (melanoma), the hormonal milieu in gestation and a tumour promoting microenvironment post-partum (breast cancer). Copyright © 2013 The Authors. Published by Elsevier Ltd.. All rights reserved.

  8. Region of the eye. Strategy for the management of malignant tumours of the orbit

    International Nuclear Information System (INIS)

    Freeman, J.E.

    1984-01-01

    The strategy for the management of the various malignant tumours of the orbit was tabulated and also illustrated in diagrams. Table 1. Strategy for retinoblastoma; Table 2. Strategy for malignant melanoma: (a) intra-ocular, (b) epibulbar; Table 3. Strategy for squamous cell carcinoma: (a) conjunctival, (b) palpebral; Table 4. Strategy for basal cell carcinoma: (a) palpebral, (b) intra-orbital; Table 5. Strategy for rhabdomyosarcoma (and embryoma) of the orbit; Table 6. Strategy for lymphosarcoma of the orbit; Table 7. Strategy for other tumours of the orbit or adnexa: (A) hystiocytosis X, (B) adenocarcinoma of the lachrymal gland, (C) optic nerve glioma, (D) para-nasal sinus tumours involving orbit; Table 8. Strategy for systemic or metastatic disease involving the orbit or contents: (a) intra-ocular [(i) leukaemia, (ii) carcinoma of the breast or of the bronchus], (b) orbital or peri-orbital [(i) leukaemia, (ii) neuroblastoma, (iii) histiocytosis X, (iv) lymphoma

  9. Normal and pathological breast, the histological basis

    Energy Technology Data Exchange (ETDEWEB)

    Guinebretiere, J.M. [Department of Pathology, Centre Rene-Huguenin, 35 rue Dailly, 92210 Saint Cloud (France)]. E-mail: jm.guinebretiere@stcloud-huguenin.org; Menet, E. [Department of Pathology, Centre Rene-Huguenin, 35 rue Dailly, 92210 Saint Cloud (France); Tardivon, A. [Department of Radiology, Institut Curie, 26 rue d' Ulm, 75248 Paris Cedex 5 (France); Cherel, P. [Department of Radiology, Centre Rene-Huguenin, 35 rue Dailly, 92210 Saint Cloud (France); Vanel, D. [Department of Diagnostic Radiology, Institut Gustave-Roussy, 39 rue Camille Desmoulins, 94805 Villejuif (France)

    2005-04-01

    Breast tissue is heterogeneous, associating connective and glandular structures, which grow and change cyclically under hormonal regulation. Hormones are also thought to be the main determinant of the major benign and malignant pathologies encountered in the breast. Benign lesions are more frequent and fibrocystic changes are by far the most common among them. They usually associate different entities (adenosis, fibrosis, cysts and hyperplasia) but vary in intensity and extension. Thus, their clinical and radiographic presentation is extremely different from one patient to another. Adenofibroma is the most frequent tumour. It also undergoes modifications according to hormonal conditions. About 90% of malignant tumours are primary carcinoma. The incidence of intra-ductal carcinoma has risen dramatically since the development of screening because of its ability to induce calcification. Two mechanisms could be involved in the formation of calcification: one active (tumour cell secretion of vesicles), the other passive (necrotic cell fragments are released). Invasive carcinoma comprises numerous histological types. Stromal reactions essentially determines their shape: a fibrous reaction commonly found in ductal carcinoma creates a stellate lesion while other stroma, inflammatory (medullary carcinoma), vascular (papillary carcinoma) or mucinous determine nodular lesions whose borders push the surrounding tissue. The histological features which give rise to the radiographic pattern will be emphasised.

  10. [Feasibility and cosmetic outcome of oncoplastic surgery in breast cancer treatment].

    Science.gov (United States)

    Sherwell-Cabello, Santiago; Maffuz-Aziz, Antonio; Villegas-Carlos, Felipe; Domínguez-Reyes, Carlos; Labastida-Almendaro, Sonia; Rodríguez-Cuevas, Sergio

    2015-01-01

    Breast cancer is the leading oncological cause of death in Mexican women over 25 years old. Given the need to improve postoperative cosmetic results in patients with breast cancer, oncoplastic surgery has been developed, which allows larger tumour resections and minor cosmetic alterations. To determine the oncological feasibility and cosmetic outcome of oncoplastic surgery at the Instituto de Enfermedades de la Mama, FUCAM, AC. A review was conducted from January 2010 to July 2013, which included patients with breast cancer diagnosis treated with conventional breast-conserving surgery or with oncoplastic surgery in the Institute of Diseases of the Breast, FUCAM AC. Clinical and histopathological parameters were compared between the two groups, and a questionnaire of cosmetic satisfaction and quality of life was applied. Of the 171 patients included, 95 of them were treated with conventional breast-conserving surgery and 76 with oncoplastic surgery. Pathological tumour size was significantly larger in patients treated with oncoplastic surgery (p = 0.002). There were no differences found between the groups as regards the number of patients with positive surgical margin, the rate of complications, and cosmetic satisfaction. This study demonstrates the oncological feasibility and high cosmetic satisfaction of oncoplastic surgery with minimal psycho-social impact on patients. Copyright © 2015 Academia Mexicana de Cirugía A.C. Published by Masson Doyma México S.A. All rights reserved.

  11. Clinicopathological Characteristics of Triple-negative Breast Cancers in the Northeast Region of Turkey

    Directory of Open Access Journals (Sweden)

    Bülent Yıldız

    2014-06-01

    Full Text Available Background: Triple-negative (TN breast cancer is a subtype of breast cancer characterised by a loss of estrogen receptor (ER, progesterone receptor (PR expression, and the absence of human epidermal growth factor (HER2 overexpression. Aims: To identify the relationships between clinicopathological characteristics of TN breast cancers in the northeast region of Turkey and disease free survival (DFS and overall survival (OS. Study Design: Retrospective clinical study. Methods: Seven hundred and eighty non-metastatic breast cancer patients were enrolled in this study. The relationships between TN breast cancer and other breast cancers with respect to clinicopathological characteristics, as well as DFS and OS, were studied. Results: The triple-negative phenotype was detected in 204 patients (27.1%. Patients with triple-negative breast cancer had more grade 2-3 tumours compared to those with other types of breast cancer (92.5% versus 84.3%, p=0.004. Invasive ductal carcinoma histology, on the other hand, was less prevalent in patients with TN breast cancer (77% versus 84.5%, p=0.016. No significant differences were identified between the groups in other clinicopathological variables. Relapse and mortality rates were higher in the TN group during the follow-up of both groups [57 (27.9% versus 89 (16.2%, p<0.001 for relapse; 27 (13.2% versus 37 (6.8%, p=0.005 for mortality]. The univariate analysis demonstrated shorter DFS and OS for patients with TN breast cancer compared to those with other types of breast cancer. In the multivariate analysis, patients with TN breast cancer were 2.21 times more likely to develop relapse, while the likelihood of death increased 3.21-fold (p<0.001 and p<0.001. Conclusion: Triple-negative breast cancers demonstrate a more aggressive clinical course compared to other breast cancers. More effective strategies should be developed for the treatment of this subgroup of breast cancer.

  12. Gene expression meta-analysis identifies metastatic pathways and transcription factors in breast cancer

    International Nuclear Information System (INIS)

    Thomassen, Mads; Tan, Qihua; Kruse, Torben A

    2008-01-01

    Metastasis is believed to progress in several steps including different pathways but the determination and understanding of these mechanisms is still fragmentary. Microarray analysis of gene expression patterns in breast tumors has been used to predict outcome in recent studies. Besides classification of outcome, these global expression patterns may reflect biological mechanisms involved in metastasis of breast cancer. Our purpose has been to investigate pathways and transcription factors involved in metastasis by use of gene expression data sets. We have analyzed 8 publicly available gene expression data sets. A global approach, 'gene set enrichment analysis' as well as an approach focusing on a subset of significantly differently regulated genes, GenMAPP, has been applied to rank pathway gene sets according to differential regulation in metastasizing tumors compared to non-metastasizing tumors. Meta-analysis has been used to determine overrepresentation of pathways and transcription factors targets, concordant deregulated in metastasizing breast tumors, in several data sets. The major findings are up-regulation of cell cycle pathways and a metabolic shift towards glucose metabolism reflected in several pathways in metastasizing tumors. Growth factor pathways seem to play dual roles; EGF and PDGF pathways are decreased, while VEGF and sex-hormone pathways are increased in tumors that metastasize. Furthermore, migration, proteasome, immune system, angiogenesis, DNA repair and several signal transduction pathways are associated to metastasis. Finally several transcription factors e.g. E2F, NFY, and YY1 are identified as being involved in metastasis. By pathway meta-analysis many biological mechanisms beyond major characteristics such as proliferation are identified. Transcription factor analysis identifies a number of key factors that support central pathways. Several previously proposed treatment targets are identified and several new pathways that may

  13. Imaging features of automated breast volume scanner: Correlation with molecular subtypes of breast cancer

    Energy Technology Data Exchange (ETDEWEB)

    Zheng, Feng-Yang, E-mail: fyzheng16@fudan.edu.cn [Department of Ultrasound, Zhongshan Hospital, Fudan University, Shanghai 200032 (China); Shanghai Institute of Medical Imaging, Shanghai 200032 (China); Lu, Qing, E-mail: lu.qing@zs-hospital.sh.cn [Department of Ultrasound, Zhongshan Hospital, Fudan University, Shanghai 200032 (China); Huang, Bei-Jian, E-mail: huang.beijian@zs-hospital.sh.cn [Department of Ultrasound, Zhongshan Hospital, Fudan University, Shanghai 200032 (China); Shanghai Institute of Medical Imaging, Shanghai 200032 (China); Xia, Han-Sheng, E-mail: zs12036@126.com [Department of Ultrasound, Zhongshan Hospital, Fudan University, Shanghai 200032 (China); Yan, Li-Xia, E-mail: dndyanlixia@163.com [Department of Ultrasound, Zhongshan Hospital, Fudan University, Shanghai 200032 (China); Wang, Xi, E-mail: wang.xi@zs-hospital.sh.cn [Department of Ultrasound, Zhongshan Hospital, Fudan University, Shanghai 200032 (China); Shanghai Institute of Medical Imaging, Shanghai 200032 (China); Yuan, Wei, E-mail: yuan.wei@zs-hospital.sh.cn [Department of Pathology, Zhongshan Hospital, Fudan University, Shanghai 200032 (China); Wang, Wen-Ping, E-mail: wang.wenping@zs-hospital.sh.cn [Department of Ultrasound, Zhongshan Hospital, Fudan University, Shanghai 200032 (China); Shanghai Institute of Medical Imaging, Shanghai 200032 (China)

    2017-01-15

    Highlights: • ABVS imaging features have a strong correlation with breast cancer molecular subtypes. • Retraction phenomenon on the coronal planes was the most important predictor for Luminal A and Triple Negative subtypes. • ABVS expand the scope of ultrasound in identifying breast cancer molecular subtypes. - Abstract: Objectives: To investigate the correlation between the imaging features obtained by an automated breast volume scanner (ABVS) and molecular subtypes of breast cancer. Methods: We examined 303 malignant breast tumours by ABVS for specific imaging features and by immunohistochemical analysis to determine the molecular subtype. ABVS imaging features, including retraction phenomenon, shape, margins, echogenicity, post-acoustic features, echogenic halo, and calcifications were analysed by univariate and multivariate logistic regression analyses to determine the significant predictive factors of the molecular subtypes. Results: By univariate logistic regression analysis, the predictive factors of the Luminal-A subtype (n = 128) were retraction phenomenon (odds ratio [OR] = 10.188), post-acoustic shadowing (OR = 5.112), and echogenic halo (OR = 3.263, P < 0.001). The predictive factors of the Human-epidermal-growth-factor-receptor-2-amplified subtype (n = 39) were calcifications (OR = 6.210), absence of retraction phenomenon (OR = 4.375), non-mass lesions (OR = 4.286, P < 0.001), absence of echogenic halo (OR = 3.851, P = 0.035), and post-acoustic enhancement (OR = 3.641, P = 0.008). The predictors for the Triple-Negative subtype (n = 47) were absence of retraction phenomenon (OR = 5.884), post-acoustic enhancement (OR = 5.255, P < 0.001), absence of echogenic halo (OR = 4.138, P = 0.002), and absence of calcifications (OR = 3.363, P = 0.001). Predictors for the Luminal-B subtype (n = 89) had a relatively lower association (OR ≤ 2.328). By multivariate logistic regression analysis, retraction phenomenon was the strongest independent predictor for

  14. Imaging features of automated breast volume scanner: Correlation with molecular subtypes of breast cancer

    International Nuclear Information System (INIS)

    Zheng, Feng-Yang; Lu, Qing; Huang, Bei-Jian; Xia, Han-Sheng; Yan, Li-Xia; Wang, Xi; Yuan, Wei; Wang, Wen-Ping

    2017-01-01

    Highlights: • ABVS imaging features have a strong correlation with breast cancer molecular subtypes. • Retraction phenomenon on the coronal planes was the most important predictor for Luminal A and Triple Negative subtypes. • ABVS expand the scope of ultrasound in identifying breast cancer molecular subtypes. - Abstract: Objectives: To investigate the correlation between the imaging features obtained by an automated breast volume scanner (ABVS) and molecular subtypes of breast cancer. Methods: We examined 303 malignant breast tumours by ABVS for specific imaging features and by immunohistochemical analysis to determine the molecular subtype. ABVS imaging features, including retraction phenomenon, shape, margins, echogenicity, post-acoustic features, echogenic halo, and calcifications were analysed by univariate and multivariate logistic regression analyses to determine the significant predictive factors of the molecular subtypes. Results: By univariate logistic regression analysis, the predictive factors of the Luminal-A subtype (n = 128) were retraction phenomenon (odds ratio [OR] = 10.188), post-acoustic shadowing (OR = 5.112), and echogenic halo (OR = 3.263, P < 0.001). The predictive factors of the Human-epidermal-growth-factor-receptor-2-amplified subtype (n = 39) were calcifications (OR = 6.210), absence of retraction phenomenon (OR = 4.375), non-mass lesions (OR = 4.286, P < 0.001), absence of echogenic halo (OR = 3.851, P = 0.035), and post-acoustic enhancement (OR = 3.641, P = 0.008). The predictors for the Triple-Negative subtype (n = 47) were absence of retraction phenomenon (OR = 5.884), post-acoustic enhancement (OR = 5.255, P < 0.001), absence of echogenic halo (OR = 4.138, P = 0.002), and absence of calcifications (OR = 3.363, P = 0.001). Predictors for the Luminal-B subtype (n = 89) had a relatively lower association (OR ≤ 2.328). By multivariate logistic regression analysis, retraction phenomenon was the strongest independent predictor for

  15. A FIVE-YEAR HISTOPATHOLOGICAL REVIEW OF CNS TUMOURS IN A TERTIARY CENTRE WITH EMPHASIS ON DIAGNOSTIC ASPECTS OF UNCOMMON TUMOURS

    Directory of Open Access Journals (Sweden)

    Premalatha Pidakala

    2016-06-01

    Full Text Available BACKGROUND Tumours of central nervous system (CNS are of varied histogenesis and show divergent lines of differentiation and morphological features. These tumours show specific predilection for age and sex groups, more commonly than of tumours of other systems. Though tumours of glial tissue are more common, other tumours of neural, ependymal and meningeal origin are not uncommon. Metastatic disease is the common encounter in elderly. Tumour diagnosis is not always straight forward as many non-neoplastic lesions and reactive proliferations mimic tumours. Immunohistochemistry may help in problematic cases and thus can be used as an adjuvant tool in the diagnosis of such cases in addition to the routine histopathological staining methods. An accurate histological diagnosis is of extreme importance in these sites as exact diagnosis helps in proper management and favourable clinical outcome. MATERIAL & METHODS This study is on a retrospective and prospective basis in our institution from January 2011 to January, 2016. Our institute is a tertiary care center attached to a medical college catering to the needs of a rural based population. During this period, a total of 717 central nervous system tumour specimens were received and diagnosed based on examination of Haematoxylin and Eosin stained sections of formalin fixed and paraffin embedded specimens. Immunohistochemical markers (IHC were applied in selective cases for an accurate diagnosis and a number of rare cases were diagnosed based on morphology and IHC marker studies. RESULTS Age and sex incidence and anatomic distribution of various tumours were studied. In adults, meningiomas occurred most frequently in the present study followed by nerve sheath tumours, astrocytomas, metastatic deposits, glioblastomas and pituitary adenomas. Embryonal tumours occurred frequently in children. Other rare tumours identified are amyloidogenic pituitary adenoma, central neurocytoma, glioneuronal tumour with

  16. Total {sup 18}F-dopa PET tumour uptake reflects metabolic endocrine tumour activity in patients with a carcinoid tumour

    Energy Technology Data Exchange (ETDEWEB)

    Fiebrich, Helle-Brit; Walenkamp, Annemiek M.; Vries, Elisabeth G.E. de [University Medical Centre Groningen, Department of Medical Oncology, Groningen (Netherlands); Jong, Johan R. de; Koopmans, Klaas Pieter; Dierckx, Rudi A.J.O.; Brouwers, Adrienne H. [University Medical Centre Groningen, Department of Nuclear Medicine and Molecular Imaging, Groningen (Netherlands); Kema, Ido P. [University Medical Centre Groningen, Department of Laboratory Medicine, Groningen (Netherlands); Sluiter, Wim; Links, Thera P. [University Medical Centre Groningen, Department of Endocrinology, Groningen (Netherlands)

    2011-10-15

    Positron emission tomography (PET) using 6-[{sup 18}F]fluoro-L-dihydroxyphenylalanine ({sup 18}F-dopa) has an excellent sensitivity to detect carcinoid tumour lesions. {sup 18}F-dopa tumour uptake and the levels of biochemical tumour markers are mediated by tumour endocrine metabolic activity. We evaluated whether total {sup 18}F-dopa tumour uptake on PET, defined as whole-body metabolic tumour burden (WBMTB), reflects tumour load per patient, as measured with tumour markers. Seventy-seven consecutive carcinoid patients who underwent an {sup 18}F-dopa PET scan in two previously published studies were analysed. For all tumour lesions mean standardised uptake values (SUVs) at 40% of the maximal SUV and tumour volume on {sup 18}F-dopa PET were determined and multiplied to calculate a metabolic burden per lesion. WBMTB was the sum of the metabolic burden of all individual lesions per patient. The 24-h urinary serotonin, urine and plasma 5-hydroxindoleacetic acid (5-HIAA), catecholamines (nor)epinephrine, dopamine and their metabolites, measured in urine and plasma, and serum chromogranin A served as tumour markers. All but 1 were evaluable for WBMTB; 74 patients had metastatic disease. {sup 18}F-dopa PET detected 979 lesions. SUV{sub max} on {sup 18}F-dopa PET varied up to 29-fold between individual lesions within the same patients. WBMTB correlated with urinary serotonin (r = 0.51) and urinary and plasma 5-HIAA (r = 0.78 and 0.66). WBMTB also correlated with urinary norepinephrine, epinephrine, dopamine and plasma dopamine, but not with serum chromogranin A. Tumour load per patient measured with {sup 18}F-dopa PET correlates with tumour markers of the serotonin and catecholamine pathway in urine and plasma in carcinoid patients, reflecting metabolic tumour activity. (orig.)

  17. Expression of Monocarboxylate Transporters 1, 2, and 4 in Human Tumours and Their Association with CD147 and CD44

    Directory of Open Access Journals (Sweden)

    Céline Pinheiro

    2010-01-01

    Full Text Available Monocarboxylate transporters (MCTs are important cellular pH regulators in cancer cells; however, the value of MCT expression in cancer is still poorly understood. In the present study, we analysed MCT1, MCT2, and MCT4 protein expression in breast, colon, lung, and ovary neoplasms, as well as CD147 and CD44. MCT expression frequency was high and heterogeneous among the different tumours. Comparing with normal tissues, there was an increase in MCT1 and MCT4 expressions in breast carcinoma and a decrease in MCT4 plasma membrane expression in lung cancer. There were associations between CD147 and MCT1 expressions in ovarian cancer as well as between CD147 and MCT4 in both breast and lung cancers. CD44 was only associated with MCT1 plasma membrane expression in lung cancer. An important number of MCT1 positive cases are negative for both chaperones, suggesting that MCT plasma membrane expression in tumours may depend on a yet nonidentified regulatory protein.

  18. Childhood Adrenocortical Tumours: a Review

    Directory of Open Access Journals (Sweden)

    Marques-Pereira Rosana

    2006-05-01

    Full Text Available Abstract Childhood adrenocortical tumour (ACT is not a common disease, but in southern Brazil the prevalence is 15 times higher than in other parts of the world. One hundred and thirty-seven patients have been identified and followed by our group over the past four decades. Affected children are predominantly girls, with a female-to-male ratio of 3.5:1 in patients below 4 years of age. Virilization alone (51.6% or mixed with Cushing's syndrome (42.0% was the predominant clinical picture observed in these patients. Tumours are unilateral, affecting both glands equally. TP53 R337H germline mutations underlie most childhood ACTs in southern Brazil. Epidemiological data from our casuistic studies revealed that this mutation has ~10% penetrance for ACT. Surgery is the definitive treatment, and a complete resection should always be attempted. Although adjuvant chemotherapy has shown some encouraging results, its influence on overall outcome is small. The survival rate is directly correlated to tumour size; patients with small, completely excised tumours have survival rates close to 90%, whereas in those patients with inoperable tumours and/or metastatic disease it is less than 10%. In the group of patients with large, excisable tumours, half of them have an intermediate outcome. Recent molecular biology techniques and genomic approaches may help us to better understand the pathogenesis of ACT, the risk of developing a tumour when TP53 R337H is present, and to predict its outcome. An ongoing pilot study consisting of close monitoring of healthy carriers of the TP53 R337H mutation - siblings and first-degree relatives of known affected cases - aims at the early detection of ACTs and an improvement of the cure rate.

  19. Knowledge and opinions on oncoplastic surgery among breast and plastic surgeons

    DEFF Research Database (Denmark)

    Carstensen, Lena Felicia; Rose, Michael; Bentzon, Niels

    2015-01-01

    surgeons and 22 plastic surgeons; the response rate was 67%. All breast surgery units had an established cooperation with plastic surgeons. Most breast surgeons used unilateral displacement techniques; plastic surgeons also included breast reduction techniques and replacement with local flaps. Almost all...... of implementation of OPS in Denmark. METHODS: An electronic questionnaire was sent to breast and plastic surgeons performing breast cancer treatment. The questionnaire included demographics, education, experience with operative procedures and opinions on OPS. RESULTS: The questionnaire was sent to 50 breast...... symmetrisation procedures were performed by plastic surgeons. Breast surgeons had sought more specific education, both international observerships and specific courses. In both groups of surgeons, the majority expressed that both tumour removal and reconstruction should be performed by doctors of their own...

  20. Sildenafil citrate improves the delivery and anticancer activity of doxorubicin formulations in a mouse model of breast cancer.

    Science.gov (United States)

    Greish, Khaled; Fateel, Maryam; Abdelghany, Sara; Rachel, Nanitha; Alimoradi, Houman; Bakhiet, Moiz; Alsaie, Ahmed

    2017-11-21

    Sildenafil is an approved drug for the treatment of erectile dysfunction. The drug exerts its action through the relaxation of smooth muscles and the modulation of vascular endothelial permeability. In this work, we tested whether the aforementioned effects of sildenafil on tumour vasculatures could result in an improvement of anticancer drug concentration in tumour tissues and hence improves its anticancer effect. Sildenafil when added to doxorubicin showed synergistic anticancer activity against 4T1 breast cancer cells in vitro. Adding 1, 30 and 100 μM of Viagra to 1 μM of doxorubicin resulted in 1.8-fold, 6.2-fold and 21-fold statistically significant increases in its cytotoxic effect, respectively. As a result, 4T1 tumour-bearing mice showed up to 2.7-fold increase in drug concentrations of the fluorescent Dye DiI and doxorubicin in tumour tissues, as well as their nanoformulations. Animals treated with the combinations of both Sildenafil citrate and doxorubicin showed a statistically significant 4.7-fold reduction in tumour size compared to doxorubicin alone. This work highlights the effect of Sildenafil on tumour vasculatures and provides a rational for further testing the combination on breast cancer patients.