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Sample records for advanced breast tumours

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

    International Nuclear Information System (INIS)

    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

  2. DNA methylation profiling in doxorubicin treated primary locally advanced breast tumours identifies novel genes associated with survival and treatment response

    Directory of Open Access Journals (Sweden)

    Børresen-Dale Anne-Lise

    2010-03-01

    Full Text Available Abstract Background Breast cancer is the most frequent cancer in women and consists of a heterogeneous collection of diseases with distinct histopathological, genetic and epigenetic characteristics. In this study, we aimed to identify DNA methylation based biomarkers to distinguish patients with locally advanced breast cancer who may benefit from neoadjuvant doxorubicin treatment. Results We investigated quantitatively the methylation patterns in the promoter regions of 14 genes (ABCB1, ATM, BRCA1, CDH3, CDKN2A, CXCR4, ESR1, FBXW7, FOXC1, GSTP1, IGF2, HMLH1, PPP2R2B, and PTEN in 75 well-described pre-treatment samples from locally advanced breast cancer and correlated the results to the available clinical and molecular parameters. Six normal breast tissues were used as controls and 163 unselected breast cancer cases were used to validate associations with histopathological and clinical parameters. Aberrant methylation was detected in 9 out of the 14 genes including the discovery of methylation at the FOXC1 promoter. Absence of methylation at the ABCB1 promoter correlated with progressive disease during doxorubicin treatment. Most importantly, the DNA methylation status at the promoters of GSTP1, FOXC1 and ABCB1 correlated with survival, whereby the combination of methylated genes improved the subdivision with respect to the survival of the patients. In multivariate analysis GSTP1 and FOXC1 methylation status proved to be independent prognostic markers associated with survival. Conclusions Quantitative DNA methylation profiling is a powerful tool to identify molecular changes associated with specific phenotypes. Methylation at the ABCB1 or GSTP1 promoter improved overall survival probably due to prolonged availability and activity of the drug in the cell while FOXC1 methylation might be a protective factor against tumour invasiveness. FOXC1 proved to be general prognostic factor, while ABCB1 and GSTP1 might be predictive factors for the response

  3. 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 tum...... tumour cell survival and metastases. Brain metastases frequently occur in patients with advanced breast cancer.Effective treatment strategies are therefore needed against brain metastasis from breast carcinoma....

  4. Breast-conserving surgery is contraindicated for recurrent giant multifocal phyllodes tumours of breast

    OpenAIRE

    Weledji, Elroy P; Enow-Orock, George; Ngowe, Marcelin N.; Aminde, Leopold

    2014-01-01

    Background The controversy between breast conserving surgery and simple mastectomy for phyllodes tumours of the breast remains because of the unpredictable nature of the disease. Although some benign tumours may show an unusually aggressive behaviour, modified radical surgery for phyllodes tumours offers no survival advantage, and recently more conservative surgical approaches have been deployed. Case presentation A 30-year-old woman with a giant multifocal tumour of the breast underwent brea...

  5. CyberKnifeR and neo-adjuvant chemotherapy for locally advanced breast tumours: results of the dose escalation phase I

    International Nuclear Information System (INIS)

    CyberKnife allows the performance of stereotactic radiotherapy of thorax tumours with accuracy and with a real time target tracking system. The authors aimed at demonstrating the interest of this system for the treatment of breast cancers. They report a phase I study of dose escalation. A neo-adjuvant based chemotherapy is associated with the irradiation. Breast surgery is performed six to eight weeks after the sixth chemotherapy session cycle. The aim was to determine the maximum tolerated dose for the hypo-fractionated radiotherapy. Cutaneous toxicity is the limiting factor. 25 patients have been treated with different dose levels (from 18,5 to 31,5 Gy). Results are promising and must be confirmed, notably through a randomized multicentre phase II study. Short communication

  6. Effects of childhood body size on breast cancer tumour characteristics

    OpenAIRE

    Li, Jingmei; Humphreys, Keith; Eriksson, Louise; Czene, Kamila; Liu, Jianjun; Hall, Per

    2010-01-01

    Introduction Although a role of childhood body size in postmenopausal breast cancer risk has been established, less is known about its influence on tumour characteristics. Methods We studied the relationships between childhood body size and tumour characteristics in a Swedish population-based case-control study consisting of 2,818 breast cancer cases and 3,111 controls. Our classification of childhood body size was derived from a nine-level somatotype. Relative risks were estimated by odds ra...

  7. Breast spindle cell tumours: about eight cases

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    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.

  8. Breast tumour visualization using 3D quantitative ultrasound methods

    Science.gov (United States)

    Gangeh, Mehrdad J.; Raheem, Abdul; Tadayyon, Hadi; Liu, Simon; Hadizad, Farnoosh; Czarnota, Gregory J.

    2016-04-01

    Breast cancer is one of the most common cancer types accounting for 29% of all cancer cases. Early detection and treatment has a crucial impact on improving the survival of affected patients. Ultrasound (US) is non-ionizing, portable, inexpensive, and real-time imaging modality for screening and quantifying breast cancer. Due to these attractive attributes, the last decade has witnessed many studies on using quantitative ultrasound (QUS) methods in tissue characterization. However, these studies have mainly been limited to 2-D QUS methods using hand-held US (HHUS) scanners. With the availability of automated breast ultrasound (ABUS) technology, this study is the first to develop 3-D QUS methods for the ABUS visualization of breast tumours. Using an ABUS system, unlike the manual 2-D HHUS device, the whole patient's breast was scanned in an automated manner. The acquired frames were subsequently examined and a region of interest (ROI) was selected in each frame where tumour was identified. Standard 2-D QUS methods were used to compute spectral and backscatter coefficient (BSC) parametric maps on the selected ROIs. Next, the computed 2-D parameters were mapped to a Cartesian 3-D space, interpolated, and rendered to provide a transparent color-coded visualization of the entire breast tumour. Such 3-D visualization can potentially be used for further analysis of the breast tumours in terms of their size and extension. Moreover, the 3-D volumetric scans can be used for tissue characterization and the categorization of breast tumours as benign or malignant by quantifying the computed parametric maps over the whole tumour volume.

  9. Assessment of breast cancer tumour size using six different methods

    Energy Technology Data Exchange (ETDEWEB)

    Meier-Meitinger, Martina; Uder, Michael; Schulz-Wendtland, Ruediger; Adamietz, Boris [Erlangen University Hospital, Institute of Diagnostic Radiology, Erlangen (Germany); Haeberle, Lothar; Fasching, Peter A.; Bani, Mayada R.; Heusinger, Katharina; Beckmann, Matthias W. [Erlangen University Hospital, University Breast Center, Department of Gynecology and Obstetrics, Erlangen (Germany); Wachter, David [Erlangen University Hospital, Institute of Pathology, Erlangen (Germany)

    2011-06-15

    Tumour size estimates using mammography (MG), conventional ultrasound (US), compound imaging (CI) and real-time elastography (RTE) were compared with histopathological specimen sizes. The largest diameters of 97 malignant breast lesions were measured. Two US and CI measurements were made: US1/CI1 (hypoechoic nucleus only) and US2/CI2 (hypoechoic nucleus plus hyperechoic halo). Measurements were compared with histopathological tumour sizes using linear regression and Bland-Altman plots. Size prediction was best with ultrasound (US/CI/RTE: R{sup 2} 0.31-0.36); mammography was poorer (R{sup 2} = 0.19). The most accurate method was US2, while US1 and CI1 were poorest. Bland-Altman plots showed better size estimation with US2, CI2 and RTE, with low variation, while mammography showed greatest variability. Smaller tumours were better assessed than larger ones. CI2 and US2 performed best for ductal tumours and RTE for lobular cancers. Tumour size prediction accuracy did not correlate significantly with breast density, but on MG tumours were more difficult to detect in high-density tissue. The size of ductal tumours is best predicted with US2 and CI2, while for lobular cancers RTE is best. Hyperechoic tumour surroundings should be included in US and CI measurements and RTE used as an additional technique in the clinical staging process. (orig.)

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

    International Nuclear Information System (INIS)

    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-[18F] 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.)

  11. Potentialities of steady-state and transient thermography in breast tumour depth detection: A numerical study.

    Science.gov (United States)

    Amri, Amina; Pulko, Susan Helen; Wilkinson, Anthony James

    2016-01-01

    Breast thermography still has inherent limitations that prevent it from being fully accepted as a breast screening modality in medicine. The main challenges of breast thermography are to reduce false positive results and to increase the sensitivity of a thermogram. Further, it is still difficult to obtain information about tumour parameters such as metabolic heat, tumour depth and diameter from a thermogram. However, infrared technology and image processing have advanced significantly and recent clinical studies have shown increased sensitivity of thermography in cancer diagnosis. The aim of this paper is to study numerically the possibilities of extracting information about the tumour depth from steady state thermography and transient thermography after cold stress with no need to use any specific inversion technique. Both methods are based on the numerical solution of Pennes bioheat equation for a simple three-dimensional breast model. The effectiveness of two approaches used for depth detection from steady state thermography is assessed. The effect of breast density on the steady state thermal contrast has also been studied. The use of a cold stress test and the recording of transient contrasts during rewarming were found to be potentially suitable for tumour depth detection during the rewarming process. Sensitivity to parameters such as cold stress temperature and cooling time is investigated using the numerical model and simulation results reveal two prominent depth-related characteristic times which do not strongly depend on the temperature of the cold stress or on the cooling period. PMID:26522612

  12. Techniques of tumour bed boost irradiation in breast conserving therapy: Current evidence and suggested guidelines

    Energy Technology Data Exchange (ETDEWEB)

    Jalali, Rakesh; Singh, Suruchi; Budrukkar, Ashwini [Tata Memorial Hospital, Mumbai (India)

    2007-10-15

    Breast conservation surgery followed by external beam radiotherapy to breast has become the standard of care in management of early carcinoma breast. A boost to the tumour bed after whole breast radiotherapy is employed in view of the pattern of tumour bed recurrences in the index quadrant and was particularly considered in patients with some adverse histopathological characteristics such as positive margins, extensive intraductal carcinoma (EIC), lymphovascular invasion (LVI), etc. There is however, now, a conclusive evidence of improvement in local control rates after a boost radiotherapy dose in patients even without such factors and for all age groups. The maximum absolute reduction of local recurrences by the addition of boost is especially seen in young premenopausal patients. At the same time, the addition of boost is associated with increased risk of worsening of cosmesis and no clear cut survival advantage. Radiological modalities such as fluoroscopy, ultrasound and CT scan have aided in accurate delineation of tumour bed with increasing efficacy. A widespread application of these techniques might ultimately translate into improved local control with minimal cosmetic deficit. The present article discusses the role of radiotherapy boost and the means to delineate and deliver the same, identify the high risk group, optimal technique and the doses and fractionations to be used. It also discusses the extent of adverse cosmetic outcome after boost delivery, means to minimise it and relevance of tumour bed in present day scenario of advanced radiotherapy delivery techniques like (IMRT)

  13. Techniques of tumour bed boost irradiation in breast conserving therapy: Current evidence and suggested guidelines

    International Nuclear Information System (INIS)

    Breast conservation surgery followed by external beam radiotherapy to breast has become the standard of care in management of early carcinoma breast. A boost to the tumour bed after whole breast radiotherapy is employed in view of the pattern of tumour bed recurrences in the index quadrant and was particularly considered in patients with some adverse histopathological characteristics such as positive margins, extensive intraductal carcinoma (EIC), lymphovascular invasion (LVI), etc. There is however, now, a conclusive evidence of improvement in local control rates after a boost radiotherapy dose in patients even without such factors and for all age groups. The maximum absolute reduction of local recurrences by the addition of boost is especially seen in young premenopausal patients. At the same time, the addition of boost is associated with increased risk of worsening of cosmesis and no clear cut survival advantage. Radiological modalities such as fluoroscopy, ultrasound and CT scan have aided in accurate delineation of tumour bed with increasing efficacy. A widespread application of these techniques might ultimately translate into improved local control with minimal cosmetic deficit. The present article discusses the role of radiotherapy boost and the means to delineate and deliver the same, identify the high risk group, optimal technique and the doses and fractionations to be used. It also discusses the extent of adverse cosmetic outcome after boost delivery, means to minimise it and relevance of tumour bed in present day scenario of advanced radiotherapy delivery techniques like (IMRT)

  14. Numerical modelling of biopotential field for detection of breast tumour.

    Science.gov (United States)

    Ng, E Y K; Ng, W K; Sim, L S J; Rajendra Acharya, U

    2007-08-01

    Breast cancer is a disease characterised by the uncontrolled growth of abnormal cells. These cancer cells can travel through the body by way of blood or lymph nodes. Previous studies have indicated that, changes in the electrical properties of abnormal breast are more significant compared to the breast normal tissues. In the present study, a simple 2D models of breast (close to realistic), with and without artificially inserted malignant cancer were simulated, based upon electrical activity within the breast. We developed an inhomogeneous female breast model, closer to the actual, by considering a breast as a hemisphere with various layers of unequal thickness in supine condition. In order to determine the potential distribution developed due to a dipole source, isotropic homogeneous conductivity was assigned to each of these compartments and the volume conductor problem was solved using finite element method. Significant changes in the potential distribution were recoded in the malignant and normal breast regions. The surface potential decreases about 0.5%, for the small malignant region of surface area 13 mm(2) (spherical diameter=2mm). And it (surface potential) decreases about 16.4% for large malignant surface area of 615 mm(2) (spherical diameter=14 mm). Hence, the results show that, the sizes of tumours result in the reduction of surface potential and follows a fourth order polynomial equation. Thus, biofield analysis yields promising results in the detection of the breast cancer of various sizes. PMID:17145053

  15. Aggressive surgical palliation for advanced girdle tumours

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    Andrew Burd

    2012-01-01

    Full Text Available Background: The surgical management of advanced, incurable, malignant disease presents particular ethical and technical challenges. The clear goal is palliation and the surgical futility must be avoided. This case series presents some particular challenges in end-of-life surgery. Materials and Methods: Fifteen patients referred with advanced malignant disease involving a limb girdle were reviewed. Results: In one case, a patient pleaded for surgery after initially requesting a delay to seek treatment from a Chinese Traditional Herbalist. The increase in tumour bulk led to problems with surgery and the patient died in a hospital a few weeks later. This case illustrates ′futility′ not recognized and encountered. The remaining 14 patients exhibited positive palliation with improved quality of dying and appreciation expressed by patients, relatives and staff. Conclusion: In selected cases, with a skilled and experienced surgical team, patients with advanced malignant disease can still benefit from aggressive surgical palliation. The margin of error is small between palliation being attempted and futility being achieved. This considerably adds to the challenge of end-of-life surgery.

  16. Comprehensive molecular portraits of human breast tumours

    NARCIS (Netherlands)

    Koboldt, Daniel C.; Fulton, Robert S.; McLellan, Michael D.; Schmidt, Heather; Kalicki-Veizer, Joelle; McMichael, Joshua F.; Fulton, Lucinda L.; Dooling, David J.; Ding, Li; Mardis, Elaine R.; Wilson, Richard K.; Ally, Adrian; Balasundaram, Miruna; Butterfield, Yaron S. N.; Carlsen, Rebecca; Carter, Candace; Chu, Andy; Chuah, Eric; Chun, Hye-Jung E.; Coope, Robin J. N.; Dhalla, Noreen; Guin, Ranabir; Hirst, Carrie; Hirst, Martin; Holt, Robert A.; Lee, Darlene; Li, Haiyan I.; Mayo, Michael; Moore, Richard A.; Mungall, Andrew J.; Pleasance, Erin; Robertson, A. Gordon; Schein, Jacqueline E.; Shafiei, Arash; Sipahimalani, Payal; Slobodan, Jared R.; Stoll, Dominik; Tam, Angela; Thiessen, Nina; Varhol, Richard J.; Wye, Natasja; Zeng, Thomas; Zhao, Yongjun; Birol, Inanc; Jones, Steven J. M.; Marra, Marco A.; Cherniack, Andrew D.; Saksena, Gordon; Onofrio, Robert C.; Pho, Nam H.; Carter, Scott L.; Schumacher, Steven E.; Tabak, Barbara; Hernandez, Bryan; Gentry, Jeff; Nguyen, Huy; Crenshaw, Andrew; Ardlie, Kristin; Beroukhim, Rameen; Winckler, Wendy; Getz, Gad; Gabriel, Stacey B.; Meyerson, Matthew; Chin, Lynda; Park, Peter J.; Kucherlapati, Raju; Hoadley, Katherine A.; Auman, J. Todd; Fan, Cheng; Turman, Yidi J.; Shi, Yan; Li, Ling; Topal, Michael D.; He, Xiaping; Chao, Hann-Hsiang; Prat, Aleix; Silva, Grace O.; Iglesia, Michael D.; Zhao, Wei; Usary, Jerry; Berg, Jonathan S.; Adams, Michael; Booker, Jessica; Wu, Junyuan; Gulabani, Anisha; Bodenheimer, Tom; Hoyle, Alan P.; Simons, Janae V.; Soloway, Matthew G.; Mose, Lisle E.; Jefferys, Stuart R.; Balu, Saianand; Parker, Joel S.; Hayes, D. Neil; Perou, Charles M.; Malik, Simeen; Mahurkar, Swapna; Shen, Hui; Weisenberger, Daniel J.; Triche, Timothy; Lai, Phillip H.; Bootwalla, Moiz S.; Maglinte, Dennis T.; Berman, Benjamin P.; Van den Berg, David J.; Baylin, Stephen B.; Laird, Peter W.; Creighton, Chad J.; Donehower, Lawrence A.; Getz, Gad; Noble, Michael; Voet, Doug; Saksena, Gordon; Gehlenborg, Nils; DiCara, Daniel; Zhang, Juinhua; Zhang, Hailei; Wu, Chang-Jiun; Liu, Spring Yingchun; Lawrence, Michael S.; Zou, Lihua; Sivachenko, Andrey; Lin, Pei; Stojanov, Petar; Jing, Rui; Cho, Juok; Sinha, Raktim; Park, Richard W.; Nazaire, Marc-Danie; Robinson, Jim; Thorvaldsdottir, Helga; Mesirov, Jill; Park, Peter J.; Chin, Lynda; Reynolds, Sheila; Kreisberg, Richard B.; Bernard, Brady; Bressler, Ryan; Erkkila, Timo; Lin, Jake; Thorsson, Vesteinn; Zhang, Wei; Shmulevich, Ilya; Ciriello, Giovanni; Weinhold, Nils; Schultz, Nikolaus; Gao, Jianjiong; Cerami, Ethan; Gross, Benjamin; Jacobsen, Anders; Sinha, Rileen; Aksoy, B. Arman; Antipin, Yevgeniy; Reva, Boris; Shen, Ronglai; Taylor, Barry S.; Ladanyi, Marc; Sander, Chris; Anur, Pavana; Spellman, Paul T.; Lu, Yiling; Liu, Wenbin; Verhaak, Roel R. G.; Mills, Gordon B.; Akbani, Rehan; Zhang, Nianxiang; Broom, Bradley M.; Casasent, Tod D.; Wakefield, Chris; Unruh, Anna K.; Baggerly, Keith; Coombes, Kevin; Weinstein, John N.; Haussler, David; Benz, Christopher C.; Stuart, Joshua M.; Benz, Stephen C.; Zhu, Jingchun; Szeto, Christopher C.; Scott, Gary K.; Yau, Christina; Paul, Evan O.; Carlin, Daniel; Wong, Christopher; Sokolov, Artem; Thusberg, Janita; Mooney, Sean; Ng, Sam; Goldstein, Theodore C.; Ellrott, Kyle; Grifford, Mia; Wilks, Christopher; Ma, Singer; Craft, Brian; Yan, Chunhua; Hu, Ying; Meerzaman, Daoud; Gastier-Foster, Julie M.; Bowen, Jay; Ramirez, Nilsa C.; Black, Aaron D.; Pyatt, Robert E.; White, Peter; Zmuda, Erik J.; Frick, Jessica; Lichtenberg, Taram.; Brookens, Robin; George, Myra M.; Gerken, Mark A.; Harper, Hollie A.; Leraas, Kristen M.; Wise, Lisa J.; Tabler, Teresa R.; McAllister, Cynthia; Barr, Thomas; Hart-Kothari, Melissa; Tarvin, Katie; Saller, Charles; Sandusky, George; Mitchell, Colleen; Iacocca, Mary V.; Brown, Jennifer; Rabeno, Brenda; Czerwinski, Christine; Petrelli, Nicholas; Dolzhansky, Oleg; Abramov, Mikhail; Voronina, Olga; Potapova, Olga; Marks, Jeffrey R.; Suchorska, Wiktoria M.; Murawa, Dawid; Kycler, Witold; Ibbs, Matthew; Korski, Konstanty; Spychala, Arkadiusz; Murawa, Pawel; Brzezinski, Jacek J.; Perz, Hanna; Lazniak, Radoslaw; Teresiak, Marek; Tatka, Honorata; Leporowska, Ewa; Bogusz-Czerniewicz, Marta; Malicki, Julian; Mackiewicz, Andrzej; Wiznerowicz, Maciej; Van Le, Xuan; Kohl, Bernard; Viet Tien, Nguyen; Thorp, Richard; Van Bang, Nguyen; Sussman, Howard; Duc Phu, Bui; Hajek, Richard; Phi Hung, Nguyen; Viet The Phuong, Tran; Quyet Thang, Huynh; Khan, Khurram Zaki; Penny, Robert; Mallery, David; Curley, Erin; Shelton, Candace; Yena, Peggy; Ingle, James N.; Couch, Fergus J.; Lingle, Wilma L.; King, Tari A.

    2012-01-01

    We analysed primary breast cancers by genomic DNA copy number arrays, DNA methylation, exome sequencing, messenger RNA arrays, microRNA sequencing and reverse-phase protein arrays. Our ability to integrate information across platforms provided key insights into previously defined gene expression sub

  17. Attenuating Tumour Angiogenesis: A Preventive Role of Metformin against Breast Cancer

    Directory of Open Access Journals (Sweden)

    Shan Gao

    2015-01-01

    Full Text Available Metformin is one of the most widely prescribed antidiabetics for type 2 diabetes. A critical role of metformin against tumorigenesis has recently been implicated, although several studies also reported the lack of anticancer property of the antidiabetics. Given the controversies regarding the potential role of metformin against tumour progression, the effect of metformin against breast, cervical, and ovarian tumour cell lines was examined followed by in vivo assessment of metformin on tumour growth using xenograft breast cancer models. Significant inhibitory impact of metformin was observed in MCF-7, HeLa, and SKOV-3 cells, suggesting an antiproliferative property of metformin against breast, cervical, and ovarian tumour cells, respectively, with the breast tumour cells, MCF-7, being the most responsive. In vivo assessment was subsequently carried out, where mice with breast tumours were treated with metformin (20 mg/kg body weight or sterile PBS solution for 15 consecutive days. No inhibition of breast tumour progression was detected. However, tumour necrosis was significantly increased in the metformin-treated group, accompanied by decreased capillary formation within the tumours. Thus, despite the lack of short-term benefit of metformin against tumour progression, a preventive role of metformin against breast cancer was implicated, which is at partially attributable to the attenuation of tumour angiogenesis.

  18. Attenuating tumour angiogenesis: a preventive role of metformin against breast cancer.

    Science.gov (United States)

    Gao, Shan; Jiang, Jingcheng; Li, Pan; Song, Huijuan; Wang, Weiwei; Li, Chen; Kong, Deling

    2015-01-01

    Metformin is one of the most widely prescribed antidiabetics for type 2 diabetes. A critical role of metformin against tumorigenesis has recently been implicated, although several studies also reported the lack of anticancer property of the antidiabetics. Given the controversies regarding the potential role of metformin against tumour progression, the effect of metformin against breast, cervical, and ovarian tumour cell lines was examined followed by in vivo assessment of metformin on tumour growth using xenograft breast cancer models. Significant inhibitory impact of metformin was observed in MCF-7, HeLa, and SKOV-3 cells, suggesting an antiproliferative property of metformin against breast, cervical, and ovarian tumour cells, respectively, with the breast tumour cells, MCF-7, being the most responsive. In vivo assessment was subsequently carried out, where mice with breast tumours were treated with metformin (20 mg/kg body weight) or sterile PBS solution for 15 consecutive days. No inhibition of breast tumour progression was detected. However, tumour necrosis was significantly increased in the metformin-treated group, accompanied by decreased capillary formation within the tumours. Thus, despite the lack of short-term benefit of metformin against tumour progression, a preventive role of metformin against breast cancer was implicated, which is at partially attributable to the attenuation of tumour angiogenesis. PMID:25883966

  19. CASE SERIES ON PHYLLODES TUMOUR OF THE BREAST

    Directory of Open Access Journals (Sweden)

    Sri

    2015-11-01

    Full Text Available : BACKGROUND: Phyllodes tumor of breast is one of the rare neoplasms comprising less than 1% of all breast tumours.aim of the study is to evaluate the clinical charecteristics, treatment regimens and complications of phyllodes tumor in our institution. PATIENTS AND METHODS: We have retrospectively reviewed the medical records of 2 years from 2013 to 2015 of patients who presented to our department, government general hospital, Kakinada. RESULTS: 342 patients presented with breast tumors of which 126 are malignant and 216 are benign. Phyllodes tumor constituted 8 cases of the total breastlump cases presented in our institution from 2013 to 2015. 3 out of 8 cases are recurrent. CONCLUSION: In benign cases wide local excision with clear margins is sufficient to prevent recurrence. In recurrent and malignant cases simple mastectomy has to be done.

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

    International Nuclear Information System (INIS)

    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

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

    International Nuclear Information System (INIS)

    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

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

    KAUST Repository

    Simone, Giuseppina

    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.

  3. Are ipsilateral breast tumour invasive recurrences in young (⩽40 years) women more aggressive than their primary tumours?

    OpenAIRE

    Sigal-Zafrani, B; Bollet, M. A.; Antoni, G; Savignoni, A.; Vincent-Salomon, A; Pierga, J-Y; Salmon, R; Sastre-Garau, X; Fourquet, A

    2007-01-01

    The characteristics of ipsilateral breast tumour recurrences (IBTRs) relative to those of their primary tumours (PTs) remain scarcely studied. Of 70 young (⩽40 years) premenopausal women with IBTRs, we studied a series of 63 with paired histological data. Median follow-up since IBTR was 10 years. Rates of histological types, grades or hormonal receptors were not significantly different in PTs and in IBTRs. The concordance between IBTRs and their PTs was good for histological types. IBTRs with...

  4. Blood vessel hyperpermeability and pathophysiology in human tumour xenograft models of breast cancer: a comparison of ectopic and orthotopic tumours

    International Nuclear Information System (INIS)

    Human tumour xenografts in immune compromised mice are widely used as cancer models because they are easy to reproduce and simple to use in a variety of pre-clinical assessments. Developments in nanomedicine have led to the use of tumour xenografts in testing nanoscale delivery devices, such as nanoparticles and polymer-drug conjugates, for targeting and efficacy via the enhanced permeability and retention (EPR) effect. For these results to be meaningful, the hyperpermeable vasculature and reduced lymphatic drainage associated with tumour pathophysiology must be replicated in the model. In pre-clinical breast cancer xenograft models, cells are commonly introduced via injection either orthotopically (mammary fat pad, MFP) or ectopically (subcutaneous, SC), and the organ environment experienced by the tumour cells has been shown to influence their behaviour. To evaluate xenograft models of breast cancer in the context of EPR, both orthotopic MFP and ectopic SC injections of MDA-MB-231-H2N cells were given to NOD scid gamma (NSG) mice. Animals with matched tumours in two size categories were tested by injection of a high molecular weight dextran as a model nanocarrier. Tumours were collected and sectioned to assess dextran accumulation compared to liver tissue as a positive control. To understand the cellular basis of these observations, tumour sections were also immunostained for endothelial cells, basement membranes, pericytes, and lymphatic vessels. SC tumours required longer development times to become size matched to MFP tumours, and also presented wide size variability and ulcerated skin lesions 6 weeks after cell injection. The 3 week MFP tumour model demonstrated greater dextran accumulation than the size matched 5 week SC tumour model (for P < 0.10). Immunostaining revealed greater vascular density and thinner basement membranes in the MFP tumour model 3 weeks after cell injection. Both the MFP and SC tumours showed evidence of insufficient lymphatic drainage

  5. Blood vessel hyperpermeability and pathophysiology in human tumour xenograft models of breast cancer: a comparison of ectopic and orthotopic tumours

    Directory of Open Access Journals (Sweden)

    Ho Karyn S

    2012-12-01

    Full Text Available Abstract Background Human tumour xenografts in immune compromised mice are widely used as cancer models because they are easy to reproduce and simple to use in a variety of pre-clinical assessments. Developments in nanomedicine have led to the use of tumour xenografts in testing nanoscale delivery devices, such as nanoparticles and polymer-drug conjugates, for targeting and efficacy via the enhanced permeability and retention (EPR effect. For these results to be meaningful, the hyperpermeable vasculature and reduced lymphatic drainage associated with tumour pathophysiology must be replicated in the model. In pre-clinical breast cancer xenograft models, cells are commonly introduced via injection either orthotopically (mammary fat pad, MFP or ectopically (subcutaneous, SC, and the organ environment experienced by the tumour cells has been shown to influence their behaviour. Methods To evaluate xenograft models of breast cancer in the context of EPR, both orthotopic MFP and ectopic SC injections of MDA-MB-231-H2N cells were given to NOD scid gamma (NSG mice. Animals with matched tumours in two size categories were tested by injection of a high molecular weight dextran as a model nanocarrier. Tumours were collected and sectioned to assess dextran accumulation compared to liver tissue as a positive control. To understand the cellular basis of these observations, tumour sections were also immunostained for endothelial cells, basement membranes, pericytes, and lymphatic vessels. Results SC tumours required longer development times to become size matched to MFP tumours, and also presented wide size variability and ulcerated skin lesions 6 weeks after cell injection. The 3 week MFP tumour model demonstrated greater dextran accumulation than the size matched 5 week SC tumour model (for P  Conclusions Dextran accumulation and immunostaining results suggest that small MFP tumours best replicate the vascular permeability required to observe the EPR effect

  6. Attenuating Tumour Angiogenesis: A Preventive Role of Metformin against Breast Cancer

    OpenAIRE

    Shan Gao; Jingcheng Jiang; Pan Li; Huijuan Song; Weiwei Wang; Chen Li; Deling Kong

    2015-01-01

    Metformin is one of the most widely prescribed antidiabetics for type 2 diabetes. A critical role of metformin against tumorigenesis has recently been implicated, although several studies also reported the lack of anticancer property of the antidiabetics. Given the controversies regarding the potential role of metformin against tumour progression, the effect of metformin against breast, cervical, and ovarian tumour cell lines was examined followed by in vivo assessment of metformin on tumour ...

  7. Pharmacoeconomics of Bisphosphonates for Skeletal-Related Event Prevention in Metastatic Non-Breast Solid Tumours

    OpenAIRE

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

    2012-01-01

    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 met...

  8. 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)

    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

  9. 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.

  10. Periostin promotes immunosuppressive premetastatic niche formation to facilitate breast tumour metastasis.

    Science.gov (United States)

    Wang, Zhe; Xiong, Shanshan; Mao, Yubin; Chen, Mimi; Ma, Xiaohong; Zhou, Xueliang; Ma, Zhenling; Liu, Fan; Huang, Zhengjie; Luo, Qi; Ouyang, Gaoliang

    2016-08-01

    Periostin (POSTN) is a limiting factor in the metastatic colonization of disseminated tumour cells. However, the role of POSTN in regulating the immunosuppressive function of immature myeloid cells in tumour metastasis has not been documented. Here, we demonstrate that POSTN promotes the pulmonary accumulation of myeloid-derived suppressor cells (MDSCs) during the early stage of breast tumour metastasis. Postn deletion decreases neutrophil and monocytic cell populations in the bone marrow of mice and suppresses the accumulation of MDSCs to premetastatic sites. We also found that POSTN-deficient MDSCs display reduced activation of ERK, AKT and STAT3 and that POSTN deficiency decreases the immunosuppressive functions of MDSCs during tumour progression. Moreover, the pro-metastatic role of POSTN is largely limited to ER-negative breast cancer patients. Lysyl oxidase contributes to POSTN-promoted premetastatic niche formation and tumour metastasis. Our findings indicate that POSTN is essential for immunosuppressive premetastatic niche formation in the lungs during breast tumour metastasis and is a potential target for the prevention and treatment of breast tumour metastasis. Copyright © 2016 Pathological Society of Great Britain and Ireland. Published by John Wiley & Sons, Ltd. PMID:27193093

  11. Cell Biological Markers in Breast Tumours: Applications in cyto- and histopathology

    NARCIS (Netherlands)

    V. Kuenen-Boumeester (Vibeke)

    1998-01-01

    textabstractBreast cancer is the most common malignant tumour among women in the western world, affecting 8-12 % of the female population. In the Netherlands, breast cancer occurs yearly in IOOO per IOO,OOO women with an absolute incidence of 9,000 new cases per year. The etiology is multifactorial.

  12. 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.; Thomsen, C.; Roslind, A.; Nolsoe, C.P.

    2008-01-01

    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...

  13. Host microenvironment in breast cancer development: Inflammatory and immune cells in tumour angiogenesis and arteriogenesis

    International Nuclear Information System (INIS)

    Breast cancer progression is associated with and dependent upon robust neovascularization. It is becoming clear that tumour-associated 'normal' cells, such as immune/inflammatory cells, endothelial cells and stromal cells, conspire with cancer cells in promoting this process. In particular, infiltrating immune/inflammatory cells secrete a diverse repertoire of growth factors and proteases that enable them to enhance tumour growth by stimulating angiogenesis and, as we suggest here, by promoting 'tumour arteriogenesis' – enlargement of feeding vessels supplying the expanding tumour capillary bed. Macrophages and their chemoattractants (e.g. macrophage chemoattractant protein-1) are critical for the arteriogenic process in ischaemia, and probably also in breast neoplasia. A better understanding of these various cellular and molecular constituents of breast cancer neovascularization may be useful in designing more effective therapies

  14. 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)

    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

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

    International Nuclear Information System (INIS)

    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)

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

    International Nuclear Information System (INIS)

    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

  17. Down-regulation of osteopontin attenuates breast tumour progression in vivo.

    Science.gov (United States)

    Chakraborty, Goutam; Jain, Shalini; Patil, Tushar V; Kundu, Gopal C

    2008-12-01

    Development of breast tumour malignancies results in enhanced expression of various oncogenic molecules. Elevated expression of osteopontin (OPN) in higher grades of breast carcinoma correlates with enhanced expressions of several oncogenic molecules (urokinase-type plasminogen activator [uPA], matrix metalloproteinase-2/-9 [MMP-2 and -9]) and increased angiogenic potential of breast carcinoma. In this study, using in vitro and multiple in vivo models, we have demonstrated that silencing of OPN by its specific small interfering RNA (siRNA) down-regulates the expressions of oncogenic molecules such as uPA, MMP-2 and -9 resulting in inhibition of in vitro cell motility and in vivo tumourigenicity in mice. Moreover our results demonstrated that OPN-/- mice showed slower progression of tumour growth in breast cancer model as compared to wild-type mice. Furthermore, the data showed that injection of carcinogenic compound, pristane (2, 6,10,14-tetramethylpen-tadecane) induces breast tumour progression leading to enhanced expression of OPN and other oncogenic molecules in mammary fat pad of nude- and wild-type mice but not in OPN-/- mice. However, intratumoural injection of OPN siRNA to pristane-induced tumour significantly suppressed these effects. Our data revealed that knocking down of OPN effectively curb breast cancer progression and further suggested that developing of OPN-based therapeutics might be an emerging approach for the next generation of breast cancer management. PMID:18266970

  18. 18F-FDG PET and biomarkers for tumour angiogenesis in early breast cancer

    International Nuclear Information System (INIS)

    Tumour angiogenesis is an independent and strong prognostic factor in early breast carcinoma. We performed this study to investigate the ability of 18F-FDG to detect angiogenesis in early breast carcinoma using PET/CT. Twenty consecutive patients with early (T1-T2) breast carcinoma were recruited prospectively for 18F-FDG PET/CT. The PET/CT data were used to calculate whole tumour maximum standardized uptake value (SUVmax) and mean standardized uptake value (SUVmean). All patients underwent subsequent surgery without prior chemotherapy or radiotherapy. The excised tumour underwent immunohistochemistry for vascular endothelial growth factor (VEGF), CD105 and glucose transporter protein 1 (GLUT1). The SUVmax showed the following correlation with tumour histology: CD105: r = 0.60, p = 0.005; GLUT1: r = 0.21, p = 0.373; VEGF: r = -0.16, p = 0.496. The SUVmean showed the following correlation with tumour histology: CD105: r = 0.65, p = 0.002; GLUT1: r = 0.34, p = 0.144; VEGF: r = -0.18, p = 0.443 18F-FDG uptake is highly significantly associated with angiogenesis as measured by the immunohistochemistry with CD105 for new vessel formation. Given that tumour angiogenesis is an important prognostic indicator and a predictor of treatment response, 18F-FDG PET may have a role in the management of primary breast cancer patients even in early-stage disease. (orig.)

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

    International Nuclear Information System (INIS)

    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.)

  20. 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.)

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

    International Nuclear Information System (INIS)

    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

  2. BREAST TUMOUR PRESENTING AS RECURRENT DEEP VEIN THROMBOSIS

    OpenAIRE

    2006-01-01

    Deep vein thrombosis development during the course of treatment of breast carcinoma has been well described, but carcinoma breast presenting with DVT for the first time is highly unusual. We present the case of a 45 year old women with recurrent deep vein thrombosis of left lower limb. During the second episode she was found to have infiltrating ductal carcinoma of the right breast with axillary lymph node metastasis. To our knowledge there have been only one literature report of breast carci...

  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. The Impact of Tumour Characteristics on Hereditary Breast Cancer Screening

    NARCIS (Netherlands)

    M.M.A. Tilanus-Linthorst (Madeleine)

    2006-01-01

    textabstractIn the Western world breast cancer is a fairly common disease in women, nearly one in ten is diagnosed with breast cancer during her life. Worldwide 1.200.000 women are diagnosed with breast cancer annually, in the Netherlands about 12.000, 25% of them before age 50 years 1. Worldwide th

  5. Phyllodes tumours of the breast: retrospective analysis of a University Hospital's experience.

    Science.gov (United States)

    Toh, Y F; Cheah, P L; Looi, L M; Teoh, K H; Tan, P H

    2016-04-01

    Taking cognizance of the purported variation of phyllodes tumours in Asians compared with Western populations, this study looked at phyllodes tumours of the breast diagnosed at the Department of Pathology, University of Malaya Medical Centre over an 8-year period with regards to patient profiles, tumour parameters, treatment offered and outcome. Sixty-four new cases of phyllodes tumour were diagnosed during the period, however only 30 (21 benign, 4 borderline and 5 malignant) finally qualified for entry into the study. These were followed-up for 4-102 months (average = 41.7 months). Thirteen cases (8 benign, 3 borderline, 2 malignant) were Chinese, 9 (all benign) Malay, 7 (4 benign, 1 borderline, 2 malignant) Indian and 1 (malignant) Indonesian. Prevalence of benign versus combined borderline and malignant phyllodes showed a marginally significant difference (p=0.049) between the Malays and Chinese. Patients' ages ranged from 21-70 years with a mean of 44.9 years with no significant difference in age between benign, borderline or malignant phyllodes tumours. Except for benign phyllodes tumours (mean size = 5.8 cm) being significantly smaller at presentation compared with borderline (mean size = 12.5 cm) and malignant (mean size = 15.8 cm) (ppregnancy, breast feeding, hormonal contraception and tumour laterality did not differ between the three categories. Family history of breast cancer was noted in 2 cases of benign phyllodes. Local excision was performed in 17 benign, 2 borderline and 3 malignant tumours and mastectomy in 4 benign, 2 borderline and 2 malignant tumours. Surgical clearance was not properly recorded in 10 benign phyllodes tumours. Six benign and all 4 borderline and 5 malignant tumours had clearances of <10 mm. Two benign tumours recurred locally at 15 and 49 months after local excision, however information regarding surgical clearance was not available in both cases. One patient with a malignant tumour developed a radiologically-diagnosed lung

  6. Does giant breast tumour have an increased complication risk for subcutaneous mastectomy and reconstruction?

    Directory of Open Access Journals (Sweden)

    Coban Yusuf

    2006-01-01

    Full Text Available Prosthetic breast reconstruction after subcutaneous mastectomy has some complications such as skin necrosis, loss of areola-nipple, haematoma, seroma, infection, displacement of implants, areola nipple disposition and inadequate skin construction resulting in skin wrinkles. We discuss whether giant breast tumour has an increased complication risk after the surgery, in this paper which reports a patient with giant breast tumour i.e., a large recurrent fibroadenoma in the same breast. Subcutaneous mastectomy was performed without skin reduction through submammary incision. Total muscular coverage was provided for immediate reconstruction using 350 cc gel- filled breast implant. Though haematoma or seroma didn′t exist, superficial skin necrosis developed subsequently. Spontaneous epithelisation was observed all of the necrosis area to cover this area in a few weeks. Initially, skin coverage and areola nipple position on the breast was acceptable, but 8 months after the operation, skin reconstruction was not good enough to provide good skin envelope. Just as as skin lack or insufficiency is a severe problem in breast reconstruction, excess skin may be another trouble for providing an acceptable breast shape.

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

    International Nuclear Information System (INIS)

    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

  8. 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.

  9. Large expansion of morphologically heterogeneous mammary epithelial cells, including the luminal phenotype, from human breast tumours

    Czech Academy of Sciences Publication Activity Database

    Krásná, Luboslava; Dudorkinová, D.; Vedralová, J.; Veselý, Pavel; Pokorná, Eva; Kudláčková, I.; Chaloupková, Alena; Petruželka, L.; Daneš, J.; Matoušková, Eva

    2002-01-01

    Roč. 2002, č. 71 (2002), s. 219-235. ISSN 0167-6806 Institutional research plan: CEZ:AV0Z5052915 Keywords : human breast tumours * in vitro cultivation * keratins Subject RIV: EB - Genetics ; Molecular Biology Impact factor: 3.132, year: 2002

  10. Parametric study of the biopotential equation for breast tumour identification using ANOVA and Taguchi method.

    Science.gov (United States)

    Ng, Eddie Y K; Ng, W Kee

    2006-03-01

    Extensive literatures have shown significant trend of progressive electrical changes according to the proliferative characteristics of breast epithelial cells. Physiologists also further postulated that malignant transformation resulted from sustained depolarization and a failure of the cell to repolarize after cell division, making the area where cancer develops relatively depolarized when compared to their non-dividing or resting counterparts. In this paper, we present a new approach, the Biofield Diagnostic System (BDS), which might have the potential to augment the process of diagnosing breast cancer. This technique was based on the efficacy of analysing skin surface electrical potentials for the differential diagnosis of breast abnormalities. We developed a female breast model, which was close to the actual, by considering the breast as a hemisphere in supine condition with various layers of unequal thickness. Isotropic homogeneous conductivity was assigned to each of these compartments and the volume conductor problem was solved using finite element method to determine the potential distribution developed due to a dipole source. Furthermore, four important parameters were identified and analysis of variance (ANOVA, Yates' method) was performed using design (n = number of parameters, 4). The effect and importance of these parameters were analysed. The Taguchi method was further used to optimise the parameters in order to ensure that the signal from the tumour is maximum as compared to the noise from other factors. The Taguchi method used proved that probes' source strength, tumour size and location of tumours have great effect on the surface potential field. For best results on the breast surface, while having the biggest possible tumour size, low amplitudes of current should be applied nearest to the breast surface. PMID:16929931

  11. The devil is in the methods: lineage tracing, functional screens and sequencing, hormones, tumour-stroma interactions, and expansion of human breast tumours as xenografts

    OpenAIRE

    dM Vivanco, María; Stingl, John; Clarke, Robert B.; Bentires-Alj, Mohamed

    2011-01-01

    The meeting of the European Network for Breast Development and Cancer (ENBDC) on 'Methods in Mammary Gland Development and Cancer' has become an annual international rendezvous for scientists with interests in the normal and neoplastic breast. The third meeting in this series, held in April-May 2011 in Weggis, Switzerland, focussed on functional screens and sequencing, hormones, lineage tracing, tumor-stroma interactions and the expansion of human breast tumours as xenografts.

  12. Feasibility of breast conservation after neoadjuvant taxene based chemotherapy in locally advanced breast cancer: a Prospective Phase I trial

    Directory of Open Access Journals (Sweden)

    El-Sayed Mohamed I

    2010-08-01

    Full Text Available Abstract Background Neoadjuvant chemotherapy is the standard care for locally advanced breast cancer. Our study aimed at evaluating the feasibility of breast conversation surgery (BCS after neoadjuvant chemotherapy. Patients and methods Forty five patients had stage IIB (except those with T2N1 disease and stage IIIA were selected to 3 cycles taxane-based neoadjuvant chemotherapy. Patient who had tumours ≤5 cm underwent a tentative BCS while patients who had tumour size >5 cm underwent radical surgery. Negative margin is essential for BCS. Adjuvant chemotherapy and 3-D radiotherapy ± hormonal treatment were given to all patients. Results Thirty four patients had BCS. Response to chemotherapy was the only statistically significant factor which influences the BCS. Incidence of local recurrence was 5.9% for patients who had BCS at a median follow up 24 months. Conclusion Breast conservation is feasible in selected cases of locally advanced, non metastatic cancer breast. We recommend that patients who have tumour size ≤4 cm after chemotherapy are the best candidates for BCS.

  13. Advanced breast cancer. 2005-2007 period

    International Nuclear Information System (INIS)

    Exploratory study was conducted, observational (cohort study), application, in order to evaluate the performance of advanced breast cancer in Clinical and Surgical Teaching Hospital 'Jose Ramon Lopez Tabrane' during the period from January 2005 to December 2007. Our main objective was to understand the behavior of advanced cancer breast cancer in our midst in the aforementioned period. Our sample consisted of 44 patients, which was applied to the study Statistical analysis for the different variables used, expressing results in tables. The 4th and 5th decade of life, and the white skin color were variable representative in our sample. The right breast and upper quadrant outside were the most frequent sites of breast cancer. More than half of the patients had a tumor larger than 5 cm and metastatic nodes. Madden mastectomy was the most frequently used providing the greatest number of complications. We recommend the importance of breast self-examination and diagnosis preclinical use of mammography. (Author)

  14. Radioresponsiveness of locally advanced breast cancer. Analysis of factors influencing the response to radiation therapy

    International Nuclear Information System (INIS)

    The radioresponsiveness of locally advanced breast cancer was studied in 239 patients treated with primary RT from 1977 to 1985. The response to RT was assessed on clinical and histological bases. For patients with no residual disease or heavily damaged residual disease in the breast and negative axillary lymph nodes after RT, the 5-year probability of local tumour control (LTC) was 90%. Response to RT was mainly affected by the T and N stages. Primary tumour size or RT dose had only a moderate influence on tumour response in this stage of the disease. The 5-year LTC was 37% for N3 and 43% for T4d conditions. Heavy tumour tissue damage was associated with microcapillary lesions, while the microvasculature around the florid tumour growth was in better condition. Microcapillaries have to be regarded as an important target in RT. The oxygen supply may worsen during fractionated RT as a result of vascular damage. Chronically hypoxic cells may be killed earlier than euoxic ones. Findings indicate that the radioresponsiveness of locally advanced breast cancer is more likely to be attributable to the biological nature of the disease than to chronically hypoxic cells present during RT. (author)

  15. Impact of family history of breast cancer on tumour characteristics, treatment, risk of second cancer and survival among men with breast cancer

    OpenAIRE

    Bouchardy Magnin, Christine; Rapiti Aylward, Elisabetta; Fioretta, Gérald; Schubert, Hyma; Chappuis, Pierre; Vlastos, Georges; Benhamou, Simone

    2013-01-01

    Male breast cancer patients have a higher risk of developing a second primary cancer, but whether this risk differs according to the family history of breast or ovarian cancers remains to be elucidated. We aimed to determine the effect of a positive family history among men diagnosed with breast cancer on tumour characteristics, treatment, second cancer occurrence and overall survival.

  16. A CLINICAL STUDY OF LOCALLY ADVANCED CARCINOMA OF BREAST

    Directory of Open Access Journals (Sweden)

    Mrinalini

    2015-06-01

    Full Text Available BACKGROUND : In India it is observed that most of the patients of breast cancer clinically present in late stage due to their ignorance of disease despite so much advancement in its detection and management. Locally advanced breast cancer (LABC accounts for 30 - 35% of all cases of breast cancers in India. This study aims to evaluate C linical features, Investigations, various Treatment modalities and the Clinico - pathological correlation & outcome of various treatment modalities of LABC, with special emphasis on Neo - adjuvant chemotherapy (NACT in Indian setting. MATERIAL AND METHOD : This was a non - randomised prospective observational study. We analyzed 57 patients of LABC Stage IIIB & IIIC presenting at Government Medical College, Nagpur, Maharashtra, a tertiary care C entre from September 2012 to November 2014. RESULTS : Stage IIIB comprised 84.21% patients while remaining 15.79% were having Stage IIIC disease. Skin involvement was observed in 91.23% patients. 15.79% showed supraclavicular lymph node involvement. 32 patients received NACT (2 to 6 cycles. Out of these 32, complete clinical response (cCR was 12.5%, partial response (cPR was 68.75% and pathological CR (pCR was 6.25% with Total Objective response (cCR+cPR 81.25%. Feasibility of Breast Conserving Surgery (BCS was observed in 12.5% patients. 25 patients underwent primary surgery followed by adjuvant chemotherapy. Modified Radical Mastectomy was performed in 89.48% patients. CONCLUSIONS : With overall clinical response of 81.25%, n eoadjuvant chemotherapy is the best treatment option for patients with Locally Advanced Breast Cancer with added advantage of in vivo testing the sensitivity of chemotherapeutic agents, early management of micrometastasis and down staging the primary tumour with feasibility of BCS. Patients presenting LABC constitute a diverse group for whic h a variety of treatment modalities should be instituted with co o rdinated treatment planning among surgeons

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

    International Nuclear Information System (INIS)

    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

  18. Detection of Circulating Tumour Cells from Blood of Breast Cancer Patients via RT-qPCR

    Energy Technology Data Exchange (ETDEWEB)

    Andergassen, Ulrich; Kölbl, Alexandra C.; Hutter, Stefan; Friese, Klaus; Jeschke, Udo, E-mail: udo.jeschke@med.uni-muenchen.de [Department of Obstetrics and Gynaecology, Ludwig Maximilians University of Munich, Munich, Maistrasse 11, D-80337 Munich (Germany)

    2013-09-25

    Breast cancer is still the most frequent cause of cancer-related death in women worldwide. Often death is not caused only by the primary tumour itself, but also by metastatic lesions. Today it is largely accepted, that these remote metastases arise out of cells, which detach from the primary tumour, enter circulation, settle down at secondary sites in the body and are called Circulating Tumour Cells (CTCs). The occurrence of such minimal residual diseases in the blood of breast cancer patients is mostly linked to a worse prognosis for therapy outcome and overall survival. Due to their very low frequency, the detection of CTCs is, still a technical challenge. RT-qPCR as a highly sensitive method could be an approach for CTC-detection from peripheral blood of breast cancer patients. This assumption is based on the fact that CTCs are of epithelial origin and therefore express a different gene panel than surrounding blood cells. For the technical approach it is necessary to identify appropriate marker genes and to correlate their gene expression levels to the number of tumour cells within a sample in an in vitro approach. After that, samples from adjuvant and metastatic patients can be analysed. This approach may lead to new concepts in diagnosis and treatment.

  19. Detection of Circulating Tumour Cells from Blood of Breast Cancer Patients via RT-qPCR

    Directory of Open Access Journals (Sweden)

    Udo Jeschke

    2013-09-01

    Full Text Available Breast cancer is still the most frequent cause of cancer-related death in women worldwide. Often death is not caused only by the primary tumour itself, but also by metastatic lesions. Today it is largely accepted, that these remote metastases arise out of cells, which detach from the primary tumour, enter circulation, settle down at secondary sites in the body and are called Circulating Tumour Cells (CTCs. The occurrence of such minimal residual diseases in the blood of breast cancer patients is mostly linked to a worse prognosis for therapy outcome and overall survival. Due to their very low frequency, the detection of CTCs is, still a technical challenge. RT-qPCR as a highly sensitive method could be an approach for CTC-detection from peripheral blood of breast cancer patients. This assumption is based on the fact that CTCs are of epithelial origin and therefore express a different gene panel than surrounding blood cells. For the technical approach it is necessary to identify appropriate marker genes and to correlate their gene expression levels to the number of tumour cells within a sample in an in vitro approach. After that, samples from adjuvant and metastatic patients can be analysed. This approach may lead to new concepts in diagnosis and treatment.

  20. Detection of Circulating Tumour Cells from Blood of Breast Cancer Patients via RT-qPCR

    International Nuclear Information System (INIS)

    Breast cancer is still the most frequent cause of cancer-related death in women worldwide. Often death is not caused only by the primary tumour itself, but also by metastatic lesions. Today it is largely accepted, that these remote metastases arise out of cells, which detach from the primary tumour, enter circulation, settle down at secondary sites in the body and are called Circulating Tumour Cells (CTCs). The occurrence of such minimal residual diseases in the blood of breast cancer patients is mostly linked to a worse prognosis for therapy outcome and overall survival. Due to their very low frequency, the detection of CTCs is, still a technical challenge. RT-qPCR as a highly sensitive method could be an approach for CTC-detection from peripheral blood of breast cancer patients. This assumption is based on the fact that CTCs are of epithelial origin and therefore express a different gene panel than surrounding blood cells. For the technical approach it is necessary to identify appropriate marker genes and to correlate their gene expression levels to the number of tumour cells within a sample in an in vitro approach. After that, samples from adjuvant and metastatic patients can be analysed. This approach may lead to new concepts in diagnosis and treatment

  1. 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.)

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

    International Nuclear Information System (INIS)

    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

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

    Directory of Open Access Journals (Sweden)

    Saleh Farid

    2007-09-01

    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 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 Conclusion Breast cancer in Kuwait seems to be more aggressive than what is currently seen in Europe, North America, Australia, and parts of Asia. Further investigations regarding the features observed in this study need to be performed.

  4. Breast Cancer with Neoductgenesis: Histopathological Criteria and Its Correlation with Mammographic and Tumour Features

    Directory of Open Access Journals (Sweden)

    Wenjing Zhou

    2014-01-01

    Full Text Available Introduction. Breast cancer with mammographic casting type calcifications, high grade DCIS with an abnormal number of ducts, periductal desmoplastic reaction, lymphocyte infiltration, and tenascin-C (TN-C overexpression has been proposed to represent a more aggressive form of breast cancer and has been denominated as breast cancer with neoductgenesis. We developed histopathological criteria for neoductgenesis in order to study reproducibility and correlation with other tumour markers. Methods. 74 cases of grades 2 and 3 DCIS, with or without an invasive component, were selected. A combined score of the degree(s of concentration of ducts, lymphocyte infiltration, and periductal fibrosis was used to classify cases as showing neoductgenesis, or not. Diagnostic reproducibility, correlation with tumour markers, and mammographic features were studied. Results. Twenty-three of 74 cases were diagnosed with neoductgenesis. The kappa value between pathologists showed moderate reproducibility (0.50 (95% CI; 0.41–0.60. Neoductgenesis correlated significantly with malignant type microcalcifications and TN-C expression (P=0.008 and 0.04 and with ER, PR, and HER2 status (P<0.00001 for all three markers. Conclusions. We developed histological criteria for breast cancer with neoductgenesis. Neoductgenesis, by our applied histopathological definition was related to more aggressive tumour biology and malignant mammographic calcifications.

  5. Palbociclib for Advanced Breast Cancer

    Science.gov (United States)

    An interim analysis of the PALOMA3 trial shows that women with hormone receptor-positive metastatic breast cancer who received palbociclib plus fulvestrant had longer progression-free survival rates than women who received a placebo plus fulvestrant.

  6. 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.

  7. Survival of women with locally advanced breast cancer at a teaching hospital in Lahore

    International Nuclear Information System (INIS)

    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)

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

    International Nuclear Information System (INIS)

    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

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

    International Nuclear Information System (INIS)

    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)

  10. Pseudoangiomatous stromal hyperplasia (PASH) tumour at the surgical scar site in a patient of carcinoma breast.

    Science.gov (United States)

    Abrari, Andleeb

    2011-01-01

    A patient on follow-up post surgery for carcinoma breast, presented with a nodule under the surgical scar. The sinister eventuality of recurrent carcinoma was clinically considered first. The lesion was biopsied and the histopathology was diagnostic of pseudoangiomatous stromal hyperplasia tumour. The nodule was excised and the patient's clinical denouement has been uneventful in the 4 months which have elapsed after this event. PMID:22688488

  11. 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

  12. Expression of membrane transporters and metabolic enzymes involved in estrone-3-sulphate disposition in human breast tumour tissues.

    Science.gov (United States)

    Banerjee, Nilasha; Miller, Naomi; Allen, Christine; Bendayan, Reina

    2014-06-01

    Two-thirds of newly diagnosed hormone-dependent (HR?) breast cancers are detected in post-menopausal patients where estrone-3-sulphate (E3S) is the predominant source for tumour estradiol. Understanding intra-tumoral fate of E3S would facilitate in the identification of novel molecular targets for HR? post-menopausal breast cancer patients. Hence this study investigates the clinical expression of (i) organic anion-transporting polypeptides (OATPs), (ii) multidrug resistance protein (MRP-1), breast cancer resistance proteins (BCRP), and (iii) sulphatase (STS), 17β-hydroxysteroid dehydrogenase (17β-HSD-1), involved in E3S uptake, efflux and metabolism, respectively. Fluorescent and brightfield images of stained tumour sections (n = 40) were acquired at 4× and 20× magnification, respectively. Marker densities were measured as the total area of positive signal divided by the surface area of the tumour section analysed and was reported as % area (ImageJ software). Tumour, stroma and non-tumour tissue areas were also quantified (Inform software), and the ratio of optical intensity per histologic area was reported as % area/tumour, % area/stroma and % area/non-tumour. Functional role of OATPs and STS was further investigated in HR? (MCF-7, T47-D, ZR-75) and HR-(MDA-MB-231) cells by transport studies conducted in the presence or absence of specific inhibitors. Amongst all the transporters and enzymes, OATPs and STS have significantly (p < 0.0001) higher expression in HR? tumour sections with highest target signals obtained from the tumour regions of the tissues. Specific OATP-mediated E3S uptake and STS-mediated metabolism were also observed in all HR? breast cancer cells. These observations suggest the potential of OATPs as novel molecular targets for HR? breast cancers. PMID:24831777

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

    International Nuclear Information System (INIS)

    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.)

  14. 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.)

  15. Diffusion-weighted imaging in breast cancer: relationship between apparent diffusion coefficient and tumour aggressiveness

    Energy Technology Data Exchange (ETDEWEB)

    Costantini, M.; Belli, P.; Rinaldi, P. [Department of Bio-Sciences and Radiological Imaging, Catholic University, Rome (Italy); Bufi, E., E-mail: reagandus@alice.i [Department of Bio-Sciences and Radiological Imaging, Catholic University, Rome (Italy); Giardina, G. [Department of Bio-Sciences and Radiological Imaging, Catholic University, Rome (Italy); Franceschini, G. [Department of Surgery, Catholic University, Rome (Italy); Petrone, G. [Department of Pathology, Catholic University, Rome (Italy); Bonomo, L. [Department of Bio-Sciences and Radiological Imaging, Catholic University, Rome (Italy)

    2010-12-15

    Aim: To assess the utility of diffusion-weighted imaging in diagnosing and characterizing breast malignancy. Materials and methods: From April 2006 to April 2009, all consecutive patients with breast cancer undergoing breast magnetic resonance imaging (MRI) and subsequent surgery in our hospital were enrolled in this study. MRI was performed using a 1.5 T MRI unit using a dedicated, bilateral, four-channel breast coil. The MRI protocol included a diffusion sequence acquired using b values of 0 and 1000 s/mm{sup 2}. For each malignant lesion the relationships between tumour grade and histology and the relative value of the apparent diffusion coefficient (ADC) were analysed. Results: There were 136 female patients with 162 lesions. Histology revealed 149 invasive carcinomas and 13 ductal carcinomas in situ. There were 34 grade 1, 61 grade 2, and 67 grade 3 lesions. The mean ADC value of all malignant lesions was 1.03 x 10{sup -3} mm{sup 2}/s. The mean ADC values for invasive and in situ carcinomas were 1.03 x 10{sup -3} mm{sup 2}/s and 1.05 x 10{sup -3} mm{sup 2}/s, respectively. The mean ADC values for grade 1, 2, and 3 tumours were 1.25 x 10{sup -3} mm{sup 2}/s, 1.02 x 10{sup -3} mm{sup 2}/s, and 0.92 x 10{sup -3} mm{sup 2}/s, respectively. A statistically significant (p < 0.001) inverse correlation was disclosed between the ADC value and the tumour grading. The mean ADC value of the 'less aggressive' group of disease (G1 and in situ lesions) was 1.19 x 10{sup -3} mm{sup 2}/s, whereas the mean ADC value of the 'more aggressive' group (G2-G3 invasive carcinomas) was 0.96 x 10{sup -3} mm{sup 2}/s (p < 0.001). Conclusion: The study confirms the usefulness of diffusion imaging in assessing the aggressiveness of breast tumours. ADC appears to be a promising parameter in the evaluation of the degree of malignancy of breast cancer tissue.

  16. Epstein-Barr Virus, Human Papillomavirus and Mouse Mammary Tumour Virus as Multiple Viruses in Breast Cancer

    OpenAIRE

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

    2012-01-01

    Background 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. Materials and Methods 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 l...

  17. FDG PET and tumour markers in the diagnosis of recurrent and metastatic breast cancer.

    Science.gov (United States)

    Siggelkow, Wulf; Rath, Werner; Buell, Udalrich; Zimny, Michael

    2004-06-01

    Breast cancer continues to be one of the most common cancers in North America and Western Europe. Positron emission tomography with 2-[fluorine-18]-fluoro-2-deoxy-D-glucose (FDG PET) represents a non-invasive functional imaging modality that is based on metabolic characteristics of malignant tumours. In breast cancer, FDG PET is more accurate than conventional methods for staging of distant metastases or local recurrences and enables early assessment of treatment response in patients undergoing primary chemotherapy. Recent data indicate a rationale for the use of FDG PET in cases of asymptomatically elevated tumour marker levels in the presence of uncertain results of conventional imaging. Despite the fact that PET cannot rule out microscopic disease, it does have particular value in providing, in a single examination, a reliable assessment of the true extent of the disease. This technique is complementary to morphological imaging for primary diagnosis, staging and re-staging. It may become the method of choice for the assessment of asymptomatic patients with elevated tumour marker levels. This method, however, cannot replace invasive procedures if microscopic disease is of clinical relevance. PMID:15146295

  18. FDG PET and tumour markers in the diagnosis of recurrent and metastatic breast cancer

    Energy Technology Data Exchange (ETDEWEB)

    Siggelkow, Wulf [Department of Obstetrics and Gynaecology, RWTH Aachen (Germany); Universitaets-Frauenklinik, Klinikum der RWTH Aachen, Pauwels-Strasse 30, 52074, Aachen (Germany); Rath, Werner [Department of Obstetrics and Gynaecology, RWTH Aachen (Germany); Buell, Udalrich; Zimny, Michael [Department of Nuclear Medicine, RWTH Aachen (Germany)

    2004-06-01

    Breast cancer continues to be one of the most common cancers in North America and Western Europe. Positron emission tomography with 2-[fluorine-18]-fluoro-2-deoxy-d-glucose (FDG PET) represents a non-invasive functional imaging modality that is based on metabolic characteristics of malignant tumours. In breast cancer, FDG PET is more accurate than conventional methods for staging of distant metastases or local recurrences and enables early assessment of treatment response in patients undergoing primary chemotherapy. Recent data indicate a rationale for the use of FDG PET in cases of asymptomatically elevated tumour marker levels in the presence of uncertain results of conventional imaging. Despite the fact that PET cannot rule out microscopic disease, it does have particular value in providing, in a single examination, a reliable assessment of the true extent of the disease. This technique is complementary to morphological imaging for primary diagnosis, staging and re-staging. It may become the method of choice for the assessment of asymptomatic patients with elevated tumour marker levels. This method, however, cannot replace invasive procedures if microscopic disease is of clinical relevance. (orig.)

  19. Influence of electrical and thermal properties on RF ablation of breast cancer: is the tumour preferentially heated?

    Directory of Open Access Journals (Sweden)

    Sandstedt Bengt

    2005-07-01

    Full Text Available Abstract Background Techniques based on radio frequency (RF energy have many applications in medicine, in particular tumour ablation. Today, mammography screening detects many breast cancers at an early stage, facilitating treatment by minimally invasive techniques such as radio frequency ablation (RFA. The breast cancer is mostly surrounded by fat, which during RFA-treatment could result in preferential heating of the tumour due to the substantial differences in electrical parameters. The object of this study was to investigate if this preferential heating existed during experimental in vitro protocols and during computer simulations. Methods Excised breast material from four patients with morphologically diagnosed breast cancers were treated with our newly developed RFA equipment. Subsequently, two finite element method (FEM models were developed; one with only fat and one with fat and an incorporated breast cancer of varying size. The FEM models were solved using temperature dependent electrical conductivity versus constant conductivity, and transient versus steady-state analyses. Results Our experimental study performed on excised breast tissue showed a preferential heating of the tumour, even if associated with long tumour strands. The fat between these tumour strands was surprisingly unaffected. Furthermore, the computer simulations demonstrated that the difference in electrical and thermal parameters between fat and tumour tissue can cause preferential heating of the tumour. The specific absorption rate (SAR distribution changed significantly when a tumour was present in fatty tissue. The degree of preferential heating depended on tissue properties, tumour shape, and placement relative to the electrode. Temperature dependent electrical conductivity increased the thermal lesion volume, but did not change the preferential heating. Transient solutions decreased the thermal lesion volume but increased the preferential heating of the tumour

  20. Predictive value of serum medroxyprogesterone acetate concentration for response in advanced or recurrent breast cancer.

    Science.gov (United States)

    Nishimura, R; Nagao, K; Matsuda, M; Baba, K; Matsuoka, Y; Yamashita, H; Fukuda, M; Higuchi, A; Ikeda, K

    1997-08-01

    Medroxyprogesterone acetate (MPA) is one of the most commonly prescribed drugs for endocrine therapy of metastatic breast cancer. In this study, the serum MPA concentration was measured by high-performance liquid chromatography (HPLC) and evaluated for its usefulness in predicting the response in 79 cases of advanced or recurrent breast cancers. Overall, 29 patients (37%) achieved an objective response. The response rate correlated significantly with the oestrogen receptor (ER) status (P = 0.03), proliferative activity determined by DNA polymerase alpha (P = 0.04), the disease-free interval (DFI) (P = 0.05) and the serum MPA concentration (P < 0.001). Patients with ER-positive tumours, lower proliferative activity, a longer (DFI) or a higher serum MPA concentration responded more frequently. The mean serum MPA concentration in the responders with ER-positive tumours (P = 0.01) or tumours with a lower proliferative activity (P = 0.008) were significantly lower than in cases with ER-negative tumours or tumours with a higher proliferative activity, respectively. Cases with soft tissue metastases showed responses at significantly lower MPA concentrations (P = 0.003) than those with bone or visceral metastases. Furthermore, there was a dramatic decrease in the MPA concentration when a responder with a high concentration became unresponsive to the therapy. Thus, the serum MPA concentration is a determining factor for the response to treatment. PMID:9337682

  1. Progress in diagnosis of breast cancer: Advances in radiology technology

    Directory of Open Access Journals (Sweden)

    J Mari Beth Linder

    2015-01-01

    Full Text Available Breast cancer is the leading cause of cancer in females between the ages of 15 and 54, and the second leading cause of cancer death in women in the United States. Diagnosis begins with detection by breast examination (clinical breast exam or breast self-exam or by radiologic studies, like mammography. Many advances in the diagnosis of breast cancer have taken place in recent years. This article will review the history of radiologic advances in the diagnosis of breast cancer. Use of technological advancements in digital breast tomosynthesis, magnetic resonance imaging, and ultrasound in breast cancer diagnosis will be presented. Advantages and disadvantages of these diagnostic interventions when compared to older, traditional X-ray films will be discussed. It is important for all nurses, including radiology and oncology nurses, to be well informed about these varied diagnostic modalities, and appreciate the fact that advances in radiologic imaging technologies can yield improved outcomes for breast cancer patients.

  2. 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

  3. Addition of vasopressin synthetic analogue [V(4)Q(5)]dDAVP to standard chemotherapy enhances tumour growth inhibition and impairs metastatic spread in aggressive breast tumour models.

    Science.gov (United States)

    Garona, Juan; Pifano, Marina; Pastrian, Maria B; Gomez, Daniel E; Ripoll, Giselle V; Alonso, Daniel F

    2016-08-01

    [V(4)Q(5)]dDAVP is a novel 2nd generation vasopressin analogue with robust antitumour activity against metastatic breast cancer. We recently reported that, by acting on vasopressin V2r membrane receptor present in tumour cells and microvascular endothelium, [V(4)Q(5)]dDAVP inhibits angiogenesis and metastatic progression of the disease without overt toxicity. Despite chemotherapy remaining as a primary therapeutic option for aggressive breast cancer, its use is limited by low selectivity and associated adverse effects. In this regard, we evaluated potential combinational benefits by adding [V(4)Q(5)]dDAVP to standard-of-care chemotherapy. In vitro, combination of [V(4)Q(5)]dDAVP with sub-IC50 concentrations of paclitaxel or carmustine resulted in a cooperative inhibition of breast cancer cell growth in comparison to single-agent therapy. In vivo antitumour efficacy of [V(4)Q(5)]dDAVP addition to chemotherapy was first evaluated using the triple-negative MDA-MB-231 breast cancer xenograft model. Tumour-bearing mice were treated with i.v. injections of [V(4)Q(5)]dDAVP (0.3 μg/kg, thrice weekly) in combination with weekly cycles of paclitaxel (10 mg/kg i.p.). After 6 weeks of treatment, combination regimen resulted in greater tumour growth inhibition compared to monotherapy. [V(4)Q(5)]dDAVP addition was also associated with reduction of local aggressiveness, and impairment of tumour invasion and infiltration of the skin. Benefits of combined therapy were confirmed in the hormone-independent and metastatic F3II breast cancer model by combining [V(4)Q(5)]dDAVP with carmustine (25 mg/kg i.p.). Interestingly, [V(4)Q(5)]dDAVP plus cytotoxic agents severely impaired colony forming ability of tumour cells and inhibited breast cancer metastasis to lung. The present study shows that [V(4)Q(5)]dDAVP may complement conventional chemotherapy by modulating metastatic progression and early stages of microtumour establishment, and thus supports further preclinical testing of

  4. mTOR inhibition in management of advanced breast cancer

    Directory of Open Access Journals (Sweden)

    Shona Nag

    2012-01-01

    Full Text Available The mTOR pathway is becoming increasingly important in several cancers including breast cancer. This review will focus on the role of its inhibition in the management of advanced breast cancer.

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

    International Nuclear Information System (INIS)

    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.

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

    Energy Technology Data Exchange (ETDEWEB)

    Johnson, S., E-mail: sarahjljohnson@gmail.co [Peninsula Radiology Academy, Plymouth International Business Park, Plymouth (United Kingdom); Brown, S.; Porter, G.; Steel, J.; Paisley, K.; Watkins, R.; Holgate, C. [Peninsula Radiology Academy, Plymouth International Business Park, Plymouth (United Kingdom)

    2011-06-15

    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.

  7. Progress in diagnosis of breast cancer: Advances in radiology technology

    OpenAIRE

    J Mari Beth Linder; Alan D Schiska

    2015-01-01

    Breast cancer is the leading cause of cancer in females between the ages of 15 and 54, and the second leading cause of cancer death in women in the United States. Diagnosis begins with detection by breast examination (clinical breast exam or breast self-exam) or by radiologic studies, like mammography. Many advances in the diagnosis of breast cancer have taken place in recent years. This article will review the history of radiologic advances in the diagnosis of breast cancer. Use of technolog...

  8. Applying machine learning approaches to improving the accuracy of breast-tumour diagnosis via fine needle aspiration

    Institute of Scientific and Technical Information of China (English)

    YUAN Qian-fei; CAI Cong-zhong; XIAO Han-guang; LIU Xing-hua

    2007-01-01

    Diagnosis and treatment of breast cancer have been improved during the last decade; however, breast cancer is still a leading cause of death among women in the whole world. Early detection and accurate diagnosis of this disease has been demonstrated an approach to long survival of the patients. As an attempt to develop a reliable diagnosing method for breast cancer, we integrated support vector machine (SVM), k-nearest neighbor and probabilistic neural network into a complex machine learning approach to detect malignant breast tumour through a set of indicators consisting of age and ten cellular features of fine-needle aspiration of breast which were ranked according to signal-to-noise ratio to identify determinants distinguishing benign breast tumours from malignant ones. The method turned out to significantly improve the diagnosis, with a sensitivity of 94.04%, a specificity of 97.37%, and an overall accuracy up to 96.24% when SVM was adopted with the sigmoid kernel function under 5-fold cross validation. The results suggest that SVM is a promising methodology to be further developed into a practical adjunct implement to help discerning benign and malignant breast tumours and thus reduce the incidence of misdiagnosis.

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

    International Nuclear Information System (INIS)

    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

  10. CyberKnife{sup R} and neo-adjuvant chemotherapy for locally advanced breast tumours: results of the dose escalation phase I; CyberKnife{sup R} et chimiotherapie neoadjuvante pour les tumeurs du sein localement evoluees: resultats de la phase I d'escalade de dose

    Energy Technology Data Exchange (ETDEWEB)

    Bondiau, P.Y.; Ferrero, J.M.; Raoust, I.; Flipo, B.; Lallement, M.; Peyrotes, I.; Chapellier, C.; Chamorey, E.; Courdi, A. [Centre Antoine-Lacassagne, Nice (France); Bahadoran, P. [CHU de Nice, Nice (France)

    2011-10-15

    CyberKnife allows the performance of stereotactic radiotherapy of thorax tumours with accuracy and with a real time target tracking system. The authors aimed at demonstrating the interest of this system for the treatment of breast cancers. They report a phase I study of dose escalation. A neo-adjuvant based chemotherapy is associated with the irradiation. Breast surgery is performed six to eight weeks after the sixth chemotherapy session cycle. The aim was to determine the maximum tolerated dose for the hypo-fractionated radiotherapy. Cutaneous toxicity is the limiting factor. 25 patients have been treated with different dose levels (from 18,5 to 31,5 Gy). Results are promising and must be confirmed, notably through a randomized multicentre phase II study. Short communication

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

    International Nuclear Information System (INIS)

    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

  12. 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.

  13. Gene expression-based classifications of fibroadenomas and phyllodes tumours of the breast.

    Science.gov (United States)

    Vidal, Maria; Peg, Vicente; Galván, Patricia; Tres, Alejandro; Cortés, Javier; Ramón y Cajal, Santiago; Rubio, Isabel T; Prat, Aleix

    2015-06-01

    Fibroepithelial tumors (FTs) of the breast are a heterogeneous group of lesions ranging from fibroadenomas (FAD) to phyllodes tumors (PT) (benign, borderline, malignant). Further understanding of their molecular features and classification might be of clinical value. In this study, we analysed the expression of 105 breast cancer-related genes, including the 50 genes of the PAM50 intrinsic subtype predictor and 12 genes of the Claudin-low subtype predictor, in a panel of 75 FTs (34 FADs, 5 juvenile FADs, 20 benign PTs, 5 borderline PTs and 11 malignant PTs) with clinical follow-up. In addition, we compared the expression profiles of FTs with those of 14 normal breast tissues and 49 primary invasive ductal carcinomas (IDCs). Our results revealed that the levels of expression of all breast cancer-related genes can discriminate the various groups of FTs, together with normal breast tissues and IDCs (False Discovery Rate genes (e.g. CCNB1 and MKI67) and mesenchymal/epithelial-related (e.g. CLDN3 and EPCAM) genes were found to be most discriminative. As expected, FADs showed the highest and lowest expression of epithelial- and proliferation-related genes, respectively, whereas malignant PTs showed the opposite expression pattern. Interestingly, the overall profile of benign PTs was found more similar to FADs and normal breast tissues than the rest of tumours, including juvenile FADs. Within the dataset of IDCs and normal breast tissues, the vast majority of FADs, juvenile FADs, benign PTs and borderline PTs were identified as Normal-like by intrinsic breast cancer subtyping, whereas 7 (63.6%) and 3 (27.3%) malignant PTs were identified as Claudin-low and Basal-like, respectively. Finally, we observed that the previously described PAM50 risk of relapse prognostic score better predicted outcome in FTs than the morphological classification, even within PTs-only. Our results suggest that classification of FTs using gene expression-based data is feasible and might provide

  14. An Approach to Breast Cancer Immunotherapy: The Apoptotic Activity of Recombinant Anti-Interleukin-6 Monoclonal Antibodies in Intact Tumour Microenvironment of Breast Carcinoma.

    Science.gov (United States)

    Abou-Shousha, S; Moaaz, M; Sheta, M; Motawea, M A

    2016-06-01

    Current work is one of our comprehensive preclinical studies, a new approach to breast cancer (BC) immunotherapy through induction of tumour cell apoptosis. Tumour growth is not just a result of uncontrolled cell proliferation but also of reduced apoptosis. High levels of interleukin-6 (IL-6) are associated with metastatic BC and correlated with poor survival as it promotes growth of tumour-initiating cells during early tumorigenesis protecting these cells from apoptosis. Therefore, this study aims at investigating the potential of anti-IL-6 monoclonal antibodies to suppress IL-6 proliferative/anti-apoptotic activities in intact tumour microenvironment of BC. Fresh sterile tumour and normal breast tissue specimens were taken from 50 female Egyptian patients with BC undergoing radical mastectomy. A unique tissue culture system designed to provide cells of each intact tumour/normal tissue sample with its proper microenvironment either supplemented or not with anti-IL-6 monoclonal antibodies. To evaluate the apoptotic activity of anti-IL-6 as a novel candidate for BC treatment strategy, we compared its effects with those obtained using tumour necrosis-related apoptosis-inducing ligand TRAIL as an established apoptotic agent. Our results revealed that levels of either anti-IL-6- or TRAIL-induced apoptosis in the tumour or normal tissue cultures were significantly higher than those in their corresponding untreated ones (P Recombinant anti-IL-6 monoclonal antibodies could represent a novel effective element of immunotherapeutic treatment strategy for BC. The selectivity and anti-apoptotic potential of anti-IL-6 is highly hopeful in IL-6- abundant BC tumour microenvironment. PMID:26971879

  15. Co-expressed peptide receptors in breast cancer as a molecular basis for in vivo multireceptor tumour targeting

    International Nuclear Information System (INIS)

    Breast cancers can express different types of peptide receptors such as somatostatin, vasoactive intestinal peptide (VIP), gastrin-releasing peptide (GRP) and NPY(Y1) receptors. The aim of this in vitro study was to evaluate which is the most appropriate peptide receptor or peptide receptor combination for in vivo diagnostic and therapeutic targeting of breast cancers. Seventy-seven primary breast cancers and 15 breast cancer lymph node metastases were investigated in vitro for their expression of somatostatin, VPAC1, GRP and NPY(Y1) receptors using in vitro receptor autoradiography on successive tissue sections with 125I-[Tyr3]-octreotide, 125I-VIP, 125I-[Tyr4]-bombesin and 125I-[Leu31,Pro34]-PYY respectively. This study identified two groups of tumours: a group of 68 tumours (88%) with at least one receptor expressed at high density (>2,000 dpm/mg tissue) that may provide a strong predictive value for successful in vivo targeting, and a group of nine tumours (12%) with no receptors or only a low density of them (1) receptors, 25 (37%) expressed VPAC1 receptors and 14 (21%) expressed somatostatin receptors. Mean density was 9,819±530 dpm/mg tissue for GRP receptors, 9,135±579 dpm/mg for NPY(Y1) receptors, 4,337±528 dpm/mg for somatostatin receptors and 3,437±306 dpm/mg for VPAC1 receptors. It is of note that tumours expressing NPY(Y1) or GRP receptors, or both, were found in 63/68 (93%) cases. Lymph node metastases showed a similar receptor profile to the corresponding primary tumour. This in vitro study strongly suggests that the combination of radiolabelled GRP and Y1 analogues should allow targeting of breast carcinomas and their lymph node metastases for in vivo peptide receptor scintigraphy and radiotherapy. (orig.)

  16. miR-10b*, a master inhibitor of the cell cycle, is down-regulated in human breast tumours

    Science.gov (United States)

    Biagioni, Francesca; Bossel Ben-Moshe, Noa; Fontemaggi, Giulia; Canu, Valeria; Mori, Federica; Antoniani, Barbara; Di Benedetto, Anna; Santoro, Raffaela; Germoni, Sabrina; De Angelis, Fernanda; Cambria, Anna; Avraham, Roi; Grasso, Giuseppe; Strano, Sabrina; Muti, Paola; Mottolese, Marcella; Yarden, Yosef; Domany, Eytan; Blandino, Giovanni

    2012-01-01

    Deregulated proliferation is a hallmark of cancer cells. Here, we show that microRNA-10b* is a master regulator of breast cancer cell proliferation and is downregulated in tumoural samples versus matched peritumoural counterparts. Two canonical CpG islands (5 kb) upstream from the precursor sequence are hypermethylated in the analysed breast cancer tissues. Ectopic delivery of synthetic microRNA-10b* in breast cancer cell lines or into xenograft mouse breast tumours inhibits cell proliferation and impairs tumour growth in vivo, respectively. We identified and validated in vitro and in vivo three novel target mRNAs of miR-10b* (BUB1, PLK1 and CCNA2), which play a remarkable role in cell cycle regulation and whose high expression in breast cancer patients is associated with reduced disease-free survival, relapse-free survival and metastasis-free survival when compared to patients with low expression. This also suggests that restoration of microRNA-10b* expression might have therapeutic promise. PMID:23125021

  17. PET/MRI and PET/CT in advanced gynaecological tumours: initial experience and comparison

    Energy Technology Data Exchange (ETDEWEB)

    Queiroz, Marcelo A.; Schulthess, Gustav von; Veit-Haibach, Patrick [University Hospital Zurich, Department Medical Radiology, Nuclear Medicine, Zurich (Switzerland); University Hospital Zurich, Department Medical Radiology, Diagnostic and Interventional Radiology, Zurich (Switzerland); University of Zurich, Zurich (Switzerland); Kubik-Huch, Rahel A.; Freiwald-Chilla, Bianka [Kantonsspital Baden AG, Department of Radiology, Baden (Switzerland); Hauser, Nik [Kantonsspital Baden AG, Department of Gynaecology, Baden (Switzerland); Froehlich, Johannes M. [Guerbet AG, Zurich (Switzerland)

    2015-08-15

    To compare the diagnostic accuracy of PET/MRI and PET/CT for staging and re-staging advanced gynaecological cancer patients as well as identify the potential benefits of each method in such a population. Twenty-six patients with suspicious or proven advanced gynaecological cancer (12 ovarian, seven cervical, one vulvar and four endometrial tumours, one uterine metastasis, and one primary peritoneal cancer) underwent whole-body imaging with a sequential trimodality PET/CT/MR system. Images were analysed regarding primary tumour detection and delineation, loco-regional lymph node staging, and abdominal/extra-abdominal distant metastasis detection (last only by PET/CT). Eighteen (69.2 %) patients underwent PET/MRI for primary staging and eight patients (30.8 %) for re-staging their gynaecological malignancies. For primary tumour delineation, PET/MRI accuracy was statistically superior to PET/CT (p < 0.001). Among the different types of cancer, PET/MRI presented better tumour delineation mainly for cervical (6/7) and endometrial (2/3) cancers. PET/MRI for local evaluation as well as PET/CT for extra-abdominal metastases had therapeutic consequences in three and one patients, respectively. PET/CT detected 12 extra-abdominal distant metastases in 26 patients. PET/MRI is superior to PET/CT for primary tumour delineation. No differences were found in detection of regional lymph node involvement and abdominal metastases detection. (orig.)

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

    International Nuclear Information System (INIS)

    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

  19. Hepatic intra-arterial chemotherapy in patients with advanced primary liver tumours

    OpenAIRE

    Spada, Francesca; Fazio, Nicola; Bonomo, Guido; Monfardini, Lorenzo; Vigna, Paolo Della; Radice, Davide; Boselli, Sabrina; Orsi, Franco

    2012-01-01

    Background: Primary liver tumours (PLTs) are currently a major health problem worldwide. The study’s aim was to investigate the feasibility, toxicity, and activity of hepatic intra-arterial chemotherapy (HIAC) in patients with advanced PLTs. Methods: We retrospectively analysed 43 patients with advanced unresectable PLT, who were consecutively treated. HIAC with 5-fluorouracil, cisplatin, and mitomycin-C was administered through a radiologically positioned temporary percutaneous catheter ever...

  20. Response to chemotherapy and association with three tumour markers in breast cancer patients in Ghana

    Directory of Open Access Journals (Sweden)

    Emmanuel Amankwaa Frempong

    2014-08-01

    Full Text Available Purpose: Oestrogen receptor (ER, progesterone receptor (PR and human epidermal growth factor 2 (HER2/neu expression in breast cancer patients predict response to chemotherapy though recorded extent vary. This retrospective study aimed to investigate the relationship between ER, PR and HER2/neu expression and response of breast cancer to chemotherapy at a tertiary hospital in Ghana. Methods: Records of all breast cancer cases seen from 2009 through 2011 were reviewed. Their receptor status, first line treatment [4 cycles of Adriamycin (60mg/m2 + Cyclophosphamide (600mg/m2], second line treatment [Capecitabine (1g/m2 + Paclitaxel (170mg/m2] and clinical response were extracted.Results: Complete remission after first and second line treatments were observed in 36 (38.3%, 95% CI: 28.5 to 48.9 and 34 (58.6%, 95% CI: .44.9 to 71.4 respectively. After both first and second line treatment 70 (74.5%, 95% CI: 64.4 - 82.9 had gone into remission. Prevalence of ER, PR, HER2/neu and Triple negative breast cancer (TNBC were 34.0% (95% CI: 24.6 to 44.5, 20.2% (95% CI: 12.6 to 29.7, 8.5% (95% CI: 3.7 to 16.1 and 59.6% (95%CI: 48.9 to 69.6 respectively. ER and PR positivity were independently associated with complete remission after first line treatment while TNBC was associated with non-remission. Conversely ER was independently associated with non-remission after second line treatment while TNBC was associated with complete remission. Conclusion: ER and TNBC status are significant predictors of complete remission and non-remission respectively after chemotherapy for breast cancer patient in Ghana.................................................................Cite this article as:Amankwaa-Frempong E, Yeboah FA, Nguah SB, Afriyie OO. Response to chemotherapy and association with three tumour markers in breast cancer patients in Ghana. Int J Cancer Ther Oncol 2014; 2(3:02034. DOI: 10.14319/ijcto.0203.4

  1. Minimal residual disease in breast cancer: an overview of circulating and disseminated tumour cells.

    Science.gov (United States)

    Tachtsidis, A; McInnes, L M; Jacobsen, N; Thompson, E W; Saunders, C M

    2016-08-01

    Within the field of cancer research, focus on the study of minimal residual disease (MRD) in the context of carcinoma has grown exponentially over the past several years. MRD encompasses circulating tumour cells (CTCs)-cancer cells on the move via the circulatory or lymphatic system, disseminated tumour cells (DTCs)-cancer cells which have escaped into a distant site (most studies have focused on bone marrow), and resistant cancer cells surviving therapy-be they local or distant, all of which may ultimately give rise to local relapse or overt metastasis. Initial studies simply recorded the presence and number of CTCs and DTCs; however recent advances are allowing assessment of the relationship between their persistence, patient prognosis and the biological properties of MRD, leading to a better understanding of the metastatic process. Technological developments for the isolation and analysis of circulating and disseminated tumour cells continue to emerge, creating new opportunities to monitor disease progression and perhaps alter disease outcome. This review outlines our knowledge to date on both measurement and categorisation of MRD in the form of CTCs and DTCs with respect to how this relates to cancer outcomes, and the hurdles and future of research into both CTCs and DTCs. PMID:27189371

  2. The expression of Dicer and Drosha in matched normal tissues, tumours and lymph node metastases in triple negative breast cancer

    International Nuclear Information System (INIS)

    Breast cancer is the most common malignancy in women world-wide. Triple negative breast cancer (TNBC) is a highly aggressive subtype that lacks expression of hormone receptors for estrogen, progesterone and human epidermal growth factor 2; and is associated with a high propensity for metastatic spread. Several studies have identified critical roles for microRNAs in breast cancer, but the role of two critical enzymes involved in microRNA biogenesis, Dicer and Drosha, is not well understood, particularly with respect to metastatic progression in this subtype. We examined the expression of Dicer and Drosha in a series of invasive 35 TNBCs with matched normal adjacent tissues (n = 18) and lymph node metastases (n = 15) using semi-quantitative real time RT-PCR. The relationship of their expression with clinical features including age at diagnosis, lymph node positivity and tumour size was analysed. We report that Dicer was significantly decreased while Drosha was significantly increased in tumours when compared to normal adjacent tissues. While there was no difference in Drosha expression in lymph node metastases when compared to the primary tumour, Dicer was significantly increased. There was no correlation between the expression of either Dicer or Drosha to age at diagnosis, lymph node positivity and tumour size. In conclusion, Dicer and Drosha are dysregulated in TNBC and matched lymph node metastases however, the clinical relevance of this is still not known. The altered expression of Dicer and Drosha may serve as markers for disrupted miRNA biogenesis in TNBC

  3. Deep tissue volume imaging of birefringence through fibre-optic needle probes for the delineation of breast tumour

    Science.gov (United States)

    Villiger, Martin; Lorenser, Dirk; McLaughlin, Robert A.; Quirk, Bryden C.; Kirk, Rodney W.; Bouma, Brett E.; Sampson, David D.

    2016-07-01

    Identifying tumour margins during breast-conserving surgeries is a persistent challenge. We have previously developed miniature needle probes that could enable intraoperative volume imaging with optical coherence tomography. In many situations, however, scattering contrast alone is insufficient to clearly identify and delineate malignant regions. Additional polarization-sensitive measurements provide the means to assess birefringence, which is elevated in oriented collagen fibres and may offer an intrinsic biomarker to differentiate tumour from benign tissue. Here, we performed polarization-sensitive optical coherence tomography through miniature imaging needles and developed an algorithm to efficiently reconstruct images of the depth-resolved tissue birefringence free of artefacts. First ex vivo imaging of breast tumour samples revealed excellent contrast between lowly birefringent malignant regions, and stromal tissue, which is rich in oriented collagen and exhibits higher birefringence, as confirmed with co-located histology. The ability to clearly differentiate between tumour and uninvolved stroma based on intrinsic contrast could prove decisive for the intraoperative assessment of tumour margins.

  4. Prevention of doxorubicin-induced alopecia by scalp cooling in patients with advanced breast cancer.

    OpenAIRE

    Anderson, J E; Hunt, J. M.; Smith, I E

    1981-01-01

    Scalp cooling with gel packs was used to try to prevent alopecia in 31 patients being treated with doxorubicin (Adriamycin), 29 for advanced breast carcinoma and two for carcinoid tumour. Twenty-eight of the 31 patients tolerated the procedure well, and 22 of these had either no hair loss or only slight loss which remained acceptable and did not require a wig. The main factor limiting success was biochemical impairment of liver function, which occurred in nine patients; of these, six had seve...

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

    International Nuclear Information System (INIS)

    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/mm2 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 mm2 (3 T)/0.9 x 0.9 mm2 (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 10-3 mm2/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.)

  6. 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.)

  7. Randomised, phase II trial comparing oral capecitabine (Xeloda®) with paclitaxel in patients with metastatic/advanced breast cancer pretreated with anthracyclines

    OpenAIRE

    Talbot, D C; Moiseyenko, V; Van Belle, S; O'Reilly, S. M.; Alba Conejo, E; Ackland, S; Eisenberg, P; Melnychuk, D.; Pienkowski, T; Burger, H-U; Laws, S.; Osterwalder, B

    2002-01-01

    Capecitabine, an oral fluoropyrimidine carbamate, was designed to generate 5-fluorouracil preferentially at the tumour site. This randomised, phase II trial evaluated the efficacy and safety of capecitabine or paclitaxel in patients with anthracycline-pretreated metastatic breast cancer. Outpatients with locally advanced and/or metastatic breast cancer whose disease was unresponsive or resistant to anthracycline therapy were randomised to 3-week cycles of intermittent oral capecitabine (1255 ...

  8. MRI volumetry for prediction of tumour response to neoadjuvant chemotherapy followed by chemoradiotherapy in locally advanced rectal cancer

    OpenAIRE

    2015-01-01

    Objective: To investigate if MRI-assessed tumour volumetry correlates with histological tumour response to neoadjuvant chemotherapy (NACT) and subsequent chemoradiotherapy (CRT) in locally advanced rectal cancer (LARC). Methods: Data from 69 prospectively enrolled patients with LARC receiving NACT followed by CRT and radical surgery were analysed. Whole-tumour volumes were contoured in T2 weighted MR images obtained pre-treatment (VPRE), after NACT (VNACT) and after the full course of NACT...

  9. A Study of The Effect of Prolactin 125I-h PRL on its Receptors in Benign and Malignant Breast Tumours

    International Nuclear Information System (INIS)

    Serum prolactin was measured in three groups of women suffering from breast tumours, and three groups of healthy subjects. In premenopausal breast cancer women (group 1), serum prolactin was increased significantly p<0.01, whereas in postmenopausal women (group 2), serum prolactin was increased also significantly but at low extent p<0.05. On the other hand the level of serum prolactin in patients with benign breast tumours did not differ from that of the healthy subjects. Prolactin receptors were investigated in three groups of breast tumour women. In the cancerous groups, prolactin receptors were detected in 44% and 33% of the premenopausal and postmenopausal breast cancer women respectively. However in the group of benign breast tumours, the receptors were detected only in 8% of the cases used. The optimum conditions of prolactin binding with its receptors were studied and revealed that the binding was protein concentratuion, time, temperature, pH and salts dendet. The concentration of prolactin receptors (number of binding sites and the affinity constant of the binding were measured by radioreceptor assay. In premenopausal group, prolactin receptors were increased significantly (p<0.001) as compared with those of benign breast tumours, but in the group of postmenopausal breast cancer women these receptors were increased significantly somewhat less than that of the premenopausal group (p<0.01). No significant variations in the affinity constant of prolactin binding were observed in the three groups studied

  10. Advance statement of consent from patients with primary CNS tumours to organ donation and elective ventilation.

    Science.gov (United States)

    Patel, Umang Jash

    2013-03-01

    A deficit in the number of organs available for transplantation persists even with an increase in donation rates. One possible choice of donor for organs that appears under-referred and/or unaccepted is patients with primary brain tumours. In spite of advances in the treatment of high-grade primary central nervous system (CNS) tumours, the prognosis remains dire. A working group on organs from donors with primary CNS tumours showed that the risk of transmission is small and outweighs the benefits of waiting for a normal donor, in survival and organ life-years, with caveats. This paper explores the possibility that, if information on organ donation were made available to patients and their families with knowledge of their inevitable fate, perhaps some will choose to donate. It would be explained that to achieve this, elective ventilation would be performed in their final moments. This would obviate the consent question because of an advance statement. It is accepted that these are sensitive matters and there will be logistic issues. This will need discussion with the public and other professionals, but it could increase the number of donors and can be extrapolated to encompass other primary CNS tumours. PMID:23303178

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

    International Nuclear Information System (INIS)

    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.)

  12. 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.

  13. 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.

  14. Liver transplantation and the role of adjuvant therapy for advanced primary liver tumours

    OpenAIRE

    Söderdahl, Gunnar

    2005-01-01

    Liver transplantation (LT) for unresectable locally advanced primary liver tumours (aPLT) is associated with an inferior survival compared to other established indications. As organ shortage in most regions is the major factor limiting the transplant rate, a careful selection of patients accepted for LT is necessary. Thus, the majority of patients with aPLT's will not be considered for LT even though a significant proportion of them may benefit from the procedure. The purpos...

  15. Phase I study of afatinib combined with nintedanib in patients with advanced solid tumours

    OpenAIRE

    Bahleda, Rastislav; Hollebecque, Antoine; Varga, Andrea; Gazzah, Anas; Massard, Christophe; Deutsch, Eric; Amellal, Nadia; Farace, Françoise; Ould-Kaci, Mahmoud; Roux, Flavien; Marzin, Kristell; Soria, Jean-Charles

    2015-01-01

    Background: This Phase I study evaluated continuous- and intermittent-dosing (every other week) of afatinib plus nintedanib in patients with advanced solid tumours. Methods: In the dose-escalation phase (n=45), maximum tolerated doses (MTDs) were determined for continuous/intermittent afatinib 10, 20, 30 or 40 mg once daily plus continuous nintedanib 150 or 200 mg twice daily. Secondary objectives included safety and efficacy. Clinical activity of continuous afatinib plus nintedanib at the MT...

  16. Combination Therapy Shows Promise for Treating Advanced Breast Cancer

    Science.gov (United States)

    Adding the drug everolimus (Afinitor®) to exemestane helped postmenopausal women whose advanced breast cancer had stopped responding to hormonal therapy live about 4 months longer without the disease progressing than women who received exemestane alone.

  17. Downregulation of miR-92a is associated with aggressive breast cancer features and increased tumour macrophage infiltration.

    Directory of Open Access Journals (Sweden)

    Sofie Nilsson

    Full Text Available BACKGROUND: MicroRNAs are small non-coding RNAs involved in the regulation of gene expression on a posttranscriptional level. These regulatory RNAs have been implicated in numerous cellular processes and are further deregulated in different cancer types, including breast cancer. MiR-92a is part of the miR-17∼92 cluster, which was first reported to be linked to tumourigenesis. However, little is known about the expression of miR-92a in breast cancer and potential associations to tumour properties. The expression of miR-92a was therefore characterized in 144 invasive breast cancer samples using in situ hybridization and related to clinico-pathological data as well as to selected key properties of the tumour stroma, including the presence of macrophages (CD68 and cancer activated fibroblasts (alpha-SMA. METHODOLOGY/PRINCIPAL FINDINGS: To measure miR-92a levels, an in situ hybridisation protocol was developed and validated using cell lines and miR-92a inhibitors. The expression in the tumour samples was objectively evaluated using digital image analysis program subtracting background activities. We found that the miR-92a expression varied between tumours and was inversely correlated to tumour grade (r = -0.276, p = 0.003 and recurrence-free survival (p = 0.008 and provided independent prognostic information in multivariate Cox analysis (HR: 0.375, CI: 0.145-0.972, p = 0.043. MiR-92a was moreover inversely correlated to the number of infiltrating macrophages in the tumour stroma (r = -0.357, p<0.001, and downregulation of miR-92a promoted cell migration (p<0.01. CONCLUSIONS/SIGNIFICANCE: This study demonstrates that downregulation of miR-92a in breast cancer is linked to key epithelial and stromal properties as well as clinical outcome.

  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...... immunohistochemistry (IHC). Tumours were regarded as TIMP-1 positive if epithelial breast cancer cells were stained using the anti-TIMP-1 monoclonal antibody VT7. RESULTS: By central assessment 75% of tumours were classified as tumour cell TIMP-1 positive. Among CEF-treated patients, individuals with TIMP-1 negative...... immunoreactivity seems to predict a favourable effect of epirubicin-containing adjuvant therapy in primary breast cancer. However, an independent study is awaited to validate the potential predictive value of TIMP-1 immunoreactivity...

  19. The development of the Canberra symptom scorecard: a tool to monitor the physical symptoms of patients with advanced tumours

    International Nuclear Information System (INIS)

    Patients with advanced (incurable) tumours usually experience a diverse burden of symptoms. Although many symptom assessment instruments are available, we examined whether these addressed tumour-related symptoms. We reviewed existing symptom assessment instruments and found a number of deficiencies such as instruments being too long or burdensome, too short, or measuring quality of life rather than tumour-related symptoms. Others focused on emotional, rather than physical symptoms. Therefore, we decided to devise a new symptom instrument. A list of 20 symptoms common in patients with advanced tumours generated from the literature and existing instruments, was ranked according to prevalence by 202 Australian clinicians. Following clinicians' responses, the list was revised and two severity assessment scales (functional severity and distress severity) added. The resultant 18-item list was assessed in 44 outpatients with advanced tumours. Patient responses indicated that a shorter questionnaire of 11 items, reflecting three main symptom clusters, provided a good representation of physical symptoms. An additional symptom that is an important predictor of survival was added, making a 12-item questionnaire, which was entitled 'The Canberra Symptom Scorecard' (CSS). For symptom severity, the distress severity scale was more appropriate than the functional severity scale. The CSS focuses on tumour-related physical symptoms. It is about to be assessed in patients with advanced tumours receiving palliative treatments, when it will also be validated against existing instruments

  20. The development of the Canberra symptom scorecard: a tool to monitor the physical symptoms of patients with advanced tumours

    Directory of Open Access Journals (Sweden)

    Shadbolt Bruce

    2003-12-01

    Full Text Available Abstract Background Patients with advanced (incurable tumours usually experience a diverse burden of symptoms. Although many symptom assessment instruments are available, we examined whether these addressed tumour-related symptoms. Methods We reviewed existing symptom assessment instruments and found a number of deficiencies such as instruments being too long or burdensome, too short, or measuring quality of life rather than tumour-related symptoms. Others focused on emotional, rather than physical symptoms. Therefore, we decided to devise a new symptom instrument. A list of 20 symptoms common in patients with advanced tumours generated from the literature and existing instruments, was ranked according to prevalence by 202 Australian clinicians. Following clinicians' responses, the list was revised and two severity assessment scales (functional severity and distress severity added. The resultant 18-item list was assessed in 44 outpatients with advanced tumours. Results Patient responses indicated that a shorter questionnaire of 11 items, reflecting three main symptom clusters, provided a good representation of physical symptoms. An additional symptom that is an important predictor of survival was added, making a 12-item questionnaire, which was entitled "The Canberra Symptom Scorecard" (CSS. For symptom severity, the distress severity scale was more appropriate than the functional severity scale. Conclusion The CSS focuses on tumour-related physical symptoms. It is about to be assessed in patients with advanced tumours receiving palliative treatments, when it will also be validated against existing instruments.

  1. First experiences with technetium-99m furifosmin as tumour-seeking agent in breast cancer and recurrent ovarian cancer

    International Nuclear Information System (INIS)

    Recent in vitro studies suggest that technetium-99m furifosmin may have tumour-seeking properties. We analysed the diagnostic value of 99mTc-furifosmin scintigraphy in nine patients with documented carcinoma of the breast and in eight patients with continued recurrent ovarian cancer. In the breast, 99mTc-furifosmin failed to visualize the primary malignant tumour and the associated malignant lymph nodes in all patients. In contrast, multiple sites of increased tracer uptake were demonstrated in one patient with acute benign inflammatory breast disease. In four of eight patients with recurrent ovarian cancer, 99mTc-furifosmin scintigraphy demonstrated early (5 min p.i.) localized increased uptake corresponding to adhesions to the bowel as diagnosed by computed tomography, but failed to reveal further abnormalities in all patients. The present study demonstrates that furifosmin is of no value in the imaging of breast cancer and recurrent ovarian cancer. These results do not continue the pattern observed in cell culture studies and are quite in contrast to the findings of mammoscintigraphy using 99mTc-methoxyisobutylisonitrile and 99mTc-tetrofosmin. (orig.). With 3 figs., 2 tabs

  2. Visualisation of calcifications and thin collagen strands in human breast tumour specimens by the diffraction-enhanced imaging technique: a comparison with conventional mammography and histology.

    Science.gov (United States)

    Keyriläinen, Jani; Fernández, Manuel; Fiedler, Stefan; Bravin, Alberto; Karjalainen-Lindsberg, Marja-Liisa; Virkkunen, Pekka; Elo, Eva-Maria; Tenhunen, Mikko; Suortti, Pekka; Thomlinson, William

    2005-02-01

    Six excised human breast tissue specimens carrying benign and malignant tumours were examined with the diffraction-enhanced imaging technique. Diffraction-enhanced images were compared with diagnostic screen-film mammograms and the correlation with histological information of the specimens was established. The enhanced visibility of calcifications, some of which were smaller than 0.15 mm in diameter, is reported in detail. Fine details of the structures such as strands of collagen and contours between glandular and adipose tissue, which are barely visible at the contrast detection limit in the conventional absorption-based mammograms, are clearly visible in the diffraction-enhanced images. Microscopic study of the stained histopathological sections unequivocally confirms the correlation of the radiographic findings with the morphologic changes in specimens. An increased soft tissue contrast and a combination of information obtained with disparate diffraction-enhanced images provide better visibility of mammographically indistinguishable features. This kind of additional structural information of the breast tissue is required to improve assessment accuracy and earlier detection of the breast lesions. These advances in image quality make the method a very promising candidate for mammography. PMID:15664286

  3. Visualisation of calcifications and thin collagen strands in human breast tumour specimens by the diffraction-enhanced imaging technique: a comparison with conventional mammography and histology

    Energy Technology Data Exchange (ETDEWEB)

    Keyrilaeinen, Jani; Fernandez, Manuel; Fiedler, Stefan; Bravin, Alberto; Karjalainen-Lindsberg, Marja-Liisa; Virkkunen, Pekka; Elo, Eva-Maria; Tenhunen, Mikko; Suortti, Pekka; Thomlinson, William

    2005-02-01

    Six excised human breast tissue specimens carrying benign and malignant tumours were examined with the diffraction-enhanced imaging technique. Diffraction-enhanced images were compared with diagnostic screen-film mammograms and the correlation with histological information of the specimens was established. The enhanced visibility of calcifications, some of which were smaller than 0.15 mm in diameter, is reported in detail. Fine details of the structures such as strands of collagen and contours between glandular and adipose tissue, which are barely visible at the contrast detection limit in the conventional absorption-based mammograms, are clearly visible in the diffraction-enhanced images. Microscopic study of the stained histopathological sections unequivocally confirms the correlation of the radiographic findings with the morphologic changes in specimens. An increased soft tissue contrast and a combination of information obtained with disparate diffraction-enhanced images provide better visibility of mammographically indistinguishable features. This kind of additional structural information of the breast tissue is required to improve assessment accuracy and earlier detection of the breast lesions. These advances in image quality make the method a very promising candidate for mammography.

  4. 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

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

    International Nuclear Information System (INIS)

    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

  6. 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.

  7. Radiotherapy for Breast Cancer: How Can it Benefit from Advancing Technology?

    Directory of Open Access Journals (Sweden)

    Tomas Kron

    2014-11-01

    Full Text Available There have been significant technological and technical advances in radiotherapy over the last 20 years. This paper presents the pertinent advances and examines their application in contemporary breast cancer (BC radiotherapy, particularly for reducing the long-term toxicity, using intensity-modulated radiation therapy, image-guided radiation therapy, and management of breathing motion. These modern technologies and techniques enable precise delivery of a highly conformal radiation dose distribution to the target volume in real-time, to optimise tumour control, and minimise treatment toxicity. They have been used for the treatment of BC in selected centres around the world. Although there is insufficient high-level evidence to support their routine application in BC at present, implementation of these technologies has been shown to be feasible, and could result in clinically meaningful long-term benefits for selected patients with BC.

  8. Accelerated partial breast irradiation with interstitial brachytherapy as second conservative treatment for ipsilateral breast tumour recurrence: Multicentric study of the GEC-ESTRO Breast Cancer Working Group

    International Nuclear Information System (INIS)

    Purpose: To analyse the clinical outcome after salvage lumpectomy and multi-catheter brachytherapy (MCB) for ipsilateral breast tumour recurrence (IBTR). Material and methods: Between 09/00 and 09/10, 217 patients presenting an IBTR underwent lumpectomy and MCB (low, pulsed, or high-dose rate). Survival rates without second local recurrence (2nd LR), distant metastasis (DM), and overall survival (OS) were analysed as well as late effects and cosmetic results. Univariate and multivariate analyses (MVA) based on IBTR data were performed to find prognostic factors for 2nd LR, DM, and OS. Results: Median follow-up after the IBTR was 3.9 years [range: 1.1–10.3]. Five and 10-year actuarial 2nd LR rates were 5.6% [range: 1.5–9.5] and 7.2% [range: 2.1–12.1], respectively. Five and 10-year actuarial DM rates were 9.6% [range: 5.7–15.2] and 19.1% [range: 7.8–28.3], respectively. Five and 10-year actuarial OS rates were 88.7% [range: 83.1–94.8] and 76.4% [range: 66.9–87.3], respectively. In MVA, histological grade was prognostic factor for 2nd LR (p = 0.008) and OS (p = 0.02); while tumour size was prognostic factor for DM (p = 0.03). G3-4 complication rate was 11%. Excellent/good cosmetic result was achieved in 85%. Conclusion: This study suggests that in case of IBTR, lumpectomy plus MCB is feasible and effective in preventing 2nd LR with an OS rate at least equivalent to those achieved with salvage mastectomy

  9. Multidisciplinary treatment for advanced and recurrent breast cancer including brachytherapy

    Energy Technology Data Exchange (ETDEWEB)

    Tsukiyama, Iwao; Ohno, Tatsuya (Tochigi Cancer Center, Utsunomiya (Japan). Hospital); Takizawa, Yoshikazu; Ikeda, Hiroshi; Egawa, Sunao; Ogino, Takashi

    1994-06-01

    Between 1986 and 1992, 10 patients (12 lesions) of advanced breast cancer were treated with multidisciplinary treatment including brachytherapy. The lesions treated included 5 primary breast tumors, 3 metastatic lesions in the contra lateral breast, 2 recurrences after external beam irradiation, 1 metastasis to the axillary lymph node and 1 metastasis to the upper arm skin. The interstitial irradiation techniques used were [sup 192]Ir low dose-rate irradiation for 5 lesions and high dose-rate for 7 lesions (including 3 with mould irradiation). External hyperthermia as performed for 6 lesions and interstitial hyperthermia were performed for 4 lesions. The local response was CR for 3 lesions, PRa for 8 lesions, PRb for 1 lesion with the local response rate being 100%. Excellent local control could be achieved by combination external and interstitial irradiation, indicating that radiotherapy is definitely useful for the treatment of advanced breast cancer. (author).

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

    International Nuclear Information System (INIS)

    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. 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. 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. 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

  11. Hypoxia and oxidative stress in breast cancer: Tumour hypoxia – therapeutic considerations

    International Nuclear Information System (INIS)

    Conclusive research has shown that regions of acute/chronic hypoxia, which exist within the majority of solid tumours, have a profound influence on the therapeutic outcome of cancer chemotherapy and radiotherapy and are a strong prognostic factor of disease progression and survival. A strong argument therefore exists for assessing the hypoxic fraction of tumours, prior to patient treatment, and to tailor this treatment accordingly. Tumour hypoxia also provides a powerful physiological stimulus that can be exploited as a tumour-specific condition, allowing for the rationale design of hypoxia-activated anticancer drugs or novel hypoxia-regulated gene therapy strategies

  12. Relaxin reduces xenograft tumour growth of human MDA-MB-231 breast cancer cells

    OpenAIRE

    Radestock, Yvonne; Hoang-Vu, Cuong; Hombach-Klonisch, Sabine

    2008-01-01

    Introduction Relaxin levels are increased in cases of human breast cancer and has been shown to promote cancer cell migration in carcinoma cells of the breast, prostate gland and thyroid gland. In oestrogen receptor alpha-negative MDA-MB-231 human breast cancer cells, relaxin was shown to down-regulate the metastasis-promoting protein S100A4 (metastasin), a highly significant prognostic factor for poor survival in breast cancer patients. The cellular mechanisms of relaxin exposure in breast c...

  13. Locally Advanced Breast Cancer: Autologous Versus Implant-based Reconstruction

    OpenAIRE

    Tanos, Grigorios; Prousskaia, Elena; Chow, Whitney; Angelaki, Anna; Cirwan, Cleona; Hamed, Hisham; Farhadi, Jian

    2016-01-01

    Background: Recent papers and guidelines agree that patients with locally advanced breast cancer (LABC) should be offered breast reconstruction. Yet, the type of reconstruction in this group of patients is still a point of controversy. Methods: One hundred fourteen patients, treated for LABC from 2007 to 2013, were divided into 3 groups based on the reconstructive option: no reconstruction (NR), implant-based/expander-based reconstruction (IBR), and autologous tissue reconstruction (ATR). We ...

  14. Advances in Optical Spectroscopy and Imaging of Breast Lesions

    Energy Technology Data Exchange (ETDEWEB)

    Demos, S; Vogel, A J; Gandjbakhche, A H

    2006-01-03

    A review is presented of recent advances in optical imaging and spectroscopy and the use of light for addressing breast cancer issues. Spectroscopic techniques offer the means to characterize tissue components and obtain functional information in real time. Three-dimensional optical imaging of the breast using various illumination and signal collection schemes in combination with image reconstruction algorithms may provide a new tool for cancer detection and monitoring of treatment.

  15. Management of locally advanced breast cancer: Evolution and current practice

    OpenAIRE

    Rustogi Ashish; Budrukkar Ashwini; Dinshaw Ketayun; Jalali Rakesh

    2005-01-01

    Locally advanced breast cancer (LABC) accounts for a sizeable number (30-60%) of breast cancer cases and is a common clinical scenario in developing countries. The treatment of LABC has evolved from single modality treatment, consisting of radical mutilating surgery or higher doses of radiotherapy in inoperable disease to multimodality management, which along with the above two included systemic therapy. Neoadjuvant chemotherapy (NACT) has made a tremendous impact on the management of ...

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

    International Nuclear Information System (INIS)

    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

  17. Women with inoperable or locally advanced breast cancer -- what characterizes them?

    DEFF Research Database (Denmark)

    El-Charnoubi, Waseem Asim Ghulam; Svendsen, Jesper Brink; Tange, Ulla Brix; Kroman, Niels

    2012-01-01

    Breast cancer is the most common cancer among Danish women. Locally advanced breast cancer occurs in a relatively large proportion of all new primary breast cancer diagnoses and for unexplained reasons 20-30% of women with breast cancer wait more than eight weeks from the initial breast cancer...

  18. Analysis of and prognostic information from disseminated tumour cells in bone marrow in primary breast cancer: a prospective observational study

    International Nuclear Information System (INIS)

    Disseminated tumour cells (DTCs) in the bone marrow of patients with breast cancer have been identified as an independent predictor of poor prognosis in patients with non-metastatic disease. This prospective study aimed to evaluate the presence and prognostic value of DTCs in the bone marrow of female patients with primary breast cancer. Between 1999 and 2003, bone marrow aspirates were obtained from patients at the time of surgery for primary invasive breast cancer. DTCs in bone marrow were identified using monoclonal antibodies against cytokeratins for detection of epithelial cells. The detection of DTCs was related to clinical follow-up with distant disease-free survival (DDFS) and breast cancer-specific survival as endpoints. Bone marrow aspirates from adult healthy bone marrow donors were analysed separately. DTCs were analysed in 401 patients, and cytokeratin-positive cells were found in 152 of these (38%). An immunofluorescence (IF) staining procedure was used in 327 patients, and immunocytochemistry (IC) was performed in 74 patients. The IF-based method resulted in 40% DTC-positive cases, whereas 30% were positive using IC (p = 0.11). The presence of DTCs in bone marrow was not significantly related to patient or tumour characteristics. The presence of DTCs was not a prognostic factor for DDFS (IF: hazards ratio [HR], 2.2; 95% confidence interval [CI], 0.63–2.2; p = 0.60; IC: HR, 0.84; 95% CI, 0.09–8.1; p = 0.88). Significant prognostic factors were lymph node metastases, oestrogen receptor positivity, Nottingham histological grade, and tumour size using Cox univariate analysis. The analyses were positive for epithelial cells in bone marrow from adult healthy donors in 19 (25%) samples. The detection of DTCs in bone marrow in primary breast cancer was previously shown to be a predictor of poor prognosis. We were not able to confirm these results in a prospective cohort including unselected patients before the standard procedure was established. Future

  19. Impact of tumour bed boost integration on acute and late toxicity in patients with breast cancer: A systematic review.

    Science.gov (United States)

    Hamilton, Daniel George; Bale, Rebecca; Jones, Claire; Fitzgerald, Emma; Khor, Richard; Knight, Kellie; Wasiak, Jason

    2016-06-01

    The purpose of this systematic review was to summarise the evidence from studies investigating the integration of tumour bed boosts into whole breast irradiation for patients with Stage 0-III breast cancer, with a focus on its impact on acute and late toxicities. A comprehensive systematic electronic search through the Ovid MEDLINE, EMBASE and PubMed databases from January 2000 to January 2015 was conducted. Studies were considered eligible if they investigated the efficacy of hypo- or normofractionated whole breast irradiation with the inclusion of a daily concurrent boost. The primary outcomes of interest were the degree of observed acute and late toxicity following radiotherapy treatment. Methodological quality assessment was performed on all included studies using either the Newcastle-Ottawa Scale or a previously published investigator-derived quality instrument. The search identified 35 articles, of which 17 satisfied our eligibility criteria. Thirteen and eleven studies reported on acute and late toxicities respectively. Grade 3 acute skin toxicity ranged from 1 to 7% whilst moderate to severe fibrosis and telangiectasia were both limited to 9%. Reported toxicity profiles were comparable to historical data at similar time-points. Studies investigating the delivery of concurrent boosts with whole breast radiotherapy courses report safe short to medium-term toxicity profiles and cosmesis rates. Whilst the quality of evidence and length of follow-up supporting these findings is low, sufficient evidence has been generated to consider concurrent boost techniques as an alternative to conventional sequential techniques. PMID:27113229

  20. Breast cancer stem cells: implications for therapy of breast cancer

    OpenAIRE

    Morrison, Brian J.; Schmidt, Chris W.; Lakhani, Sunil R; Reynolds, Brent A.; Lopez, J. Alejandro

    2008-01-01

    The concept of cancer stem cells responsible for tumour origin, maintenance, and resistance to treatment has gained prominence in the field of breast cancer research. The therapeutic targeting of these cells has the potential to eliminate residual disease and may become an important component of a multimodality treatment. Recent improvements in immunotherapy targeting of tumour-associated antigens have advanced the prospect of targeting breast cancer stem cells, an approach that might lead to...

  1. Advancement in diagnostics of the breast diseases

    International Nuclear Information System (INIS)

    System for early and effective diagnostics of breast diseases is improved; new methods for selecting women into risk group are developed; system for women examination is improved. Application of new efficient diagnostical methods in form standardized complex integrated algorithms in dependence on concrete clinical situation is developed. It is shown that puncture should be moss acevisably carried out under X-ray control with cytoguide or ultrasound examination

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

    OpenAIRE

    van Kruchten, Michel; Glaudemans, Andor W. J. M.; de Vries, Erik F. J.; Schröder, Carolien P.; de Vries, Elisabeth G.E.; Hospers, Geke A.P.

    2015-01-01

    Purpose 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-[18F]fluoro-17β-oestradiol (18F-FES) as potential marker to select breast cancer patients for oestradiol therapy. Methods Eligible pat...

  3. Phase I study of afatinib combined with nintedanib in patients with advanced solid tumours

    Science.gov (United States)

    Bahleda, Rastislav; Hollebecque, Antoine; Varga, Andrea; Gazzah, Anas; Massard, Christophe; Deutsch, Eric; Amellal, Nadia; Farace, Françoise; Ould-Kaci, Mahmoud; Roux, Flavien; Marzin, Kristell; Soria, Jean-Charles

    2015-01-01

    Background: This Phase I study evaluated continuous- and intermittent-dosing (every other week) of afatinib plus nintedanib in patients with advanced solid tumours. Methods: In the dose-escalation phase (n=45), maximum tolerated doses (MTDs) were determined for continuous/intermittent afatinib 10, 20, 30 or 40 mg once daily plus continuous nintedanib 150 or 200 mg twice daily. Secondary objectives included safety and efficacy. Clinical activity of continuous afatinib plus nintedanib at the MTD was further evaluated in an expansion phase (n=25). Results: The most frequent dose-limiting toxicities were diarrhoea (11%) and transaminase elevations (7%). Maximum tolerated doses were afatinib 30 mg continuously plus nintedanib 150 mg, and afatinib 40 mg intermittently plus nintedanib 150 mg. Treatment-related adverse events (mostly Grade ⩽3) included diarrhoea (98%), asthenia (64%), nausea (62%) and vomiting (60%). In the dose-escalation phase, two patients had partial responses (PRs) and 27 (60%) had stable disease (SD). In the expansion phase, one complete response and three PRs were observed (all non-small cell lung cancer), with SD in 13 (52%) patients. No pharmacokinetic interactions were observed. Conclusions: MTDs of continuous or intermittent afatinib plus nintedanib demonstrated a manageable safety profile with proactive management of diarrhoea. Antitumour activity was observed in patients with solid tumours. PMID:26512876

  4. Tumours and tumourous diseases

    International Nuclear Information System (INIS)

    This book on tumours and tumourous diseases comprises two parts: 1. Bone tumours and tumourous lesions. 2. Soft tissue tumours and tumourous lesions. Details are presented on pathology, diagnosis, conservative and perioperative therapy, surgical therapy, complications after resection, indicators for amputation, recommendations for follow-up treatment, radiotherapy, radionuclide therapy, alternative therapies, therapy concepts in case of metastases, tissue engineering and plastic surgery. (uke)

  5. Elevated expression of LSD1 (Lysine-specific demethylase 1 during tumour progression from pre-invasive to invasive ductal carcinoma of the breast

    Directory of Open Access Journals (Sweden)

    Serce Nuran

    2012-08-01

    Full Text Available Abstract Background Lysine-specific demethylase1 (LSD1 is a nuclear protein which belongs to the aminooxidase-enzymes playing an important role in controlling gene expression. It has also been found highly expressed in several human malignancies including breast carcinoma. Our aim was to detect LSD1 expression also in pre-invasive neoplasias of the breast. In the current study we therefore analysed LSD1 protein expression in ductal carcinoma in situ (DCIS in comparison to invasive ductal breast cancer (IDC. Methods Using immunohistochemistry we systematically analysed LSD1 expression in low grade DCIS (n = 27, intermediate grade DCIS (n = 30, high grade DCIS (n = 31 and in invasive ductal breast cancer (n = 32. SPSS version 18.0 was used for statistical analysis. Results LSD1 was differentially expressed in DCIS and invasive ductal breast cancer. Interestingly, LSD1 was significantly overexpressed in high grade DCIS versus low grade DCIS. Differences in LSD1 expression levels were also statistically significant between low/intermediate DCIS and invasive ductal breast carcinoma. Conclusions LSD1 is also expressed in pre-invasive neoplasias of the breast. Additionally, there is a gradual increase of LSD1 expression within tumour progression from pre-invasive DCIS to invasive ductal breast carcinoma. Therefore upregulation of LSD1 may be an early tumour promoting event.

  6. Quantitative DCE-MRI for prediction of pathological complete response following neoadjuvant treatment for locally advanced breast cancer: the impact of breast cancer subtypes on the diagnostic accuracy

    Energy Technology Data Exchange (ETDEWEB)

    Drisis, Stylianos; Stathopoulos, Konstantinos; Chao, Shih-Li; Lemort, Marc [Institute Jules Bordet, Radiology Department, Brussels (Belgium); Metens, Thierry [Erasme University Hospital, Radiology Department, Brussels (Belgium); Ignatiadis, Michael [Institute Jules Bordet, Oncology Department, Brussels (Belgium)

    2016-05-15

    To assess whether DCE-MRI pharmacokinetic (PK) parameters obtained before and during chemotherapy can predict pathological complete response (pCR) differently for different breast cancer groups. Eighty-four patients who received neoadjuvant chemotherapy for locally advanced breast cancer were retrospectively included. All patients underwent two DCE-MRI examinations, one before (EX1) and one during treatment (EX2). Tumours were classified into different breast cancer groups, namely triple negative (TNBC), HER2+ and ER+/HER2-, and compared with the whole population (WP). PK parameters Ktrans and Ve were extracted using a two-compartment Tofts model. At EX1, Ktrans predicted pCR for WP and TNBC. At EX2, maximum diameter (Dmax) predicted pCR for WP and ER+/HER2-. Both PK parameters predicted pCR in WP and TNBC and only Ktrans for the HER2+. pCR was predicted from relative difference (EX1 - EX2)/EX1 of Dmax and both PK parameters in the WP group and only for Ve in the TNBC group. No PK parameter could predict response for ER+/HER-. ROC comparison between WP and breast cancer groups showed higher but not statistically significant values for TNBC for the prediction of pCR Quantitative DCE-MRI can better predict pCR after neoadjuvant treatment for TNBC but not for the ER+/HER2- group. (orig.)

  7. Quantitative DCE-MRI for prediction of pathological complete response following neoadjuvant treatment for locally advanced breast cancer: the impact of breast cancer subtypes on the diagnostic accuracy

    International Nuclear Information System (INIS)

    To assess whether DCE-MRI pharmacokinetic (PK) parameters obtained before and during chemotherapy can predict pathological complete response (pCR) differently for different breast cancer groups. Eighty-four patients who received neoadjuvant chemotherapy for locally advanced breast cancer were retrospectively included. All patients underwent two DCE-MRI examinations, one before (EX1) and one during treatment (EX2). Tumours were classified into different breast cancer groups, namely triple negative (TNBC), HER2+ and ER+/HER2-, and compared with the whole population (WP). PK parameters Ktrans and Ve were extracted using a two-compartment Tofts model. At EX1, Ktrans predicted pCR for WP and TNBC. At EX2, maximum diameter (Dmax) predicted pCR for WP and ER+/HER2-. Both PK parameters predicted pCR in WP and TNBC and only Ktrans for the HER2+. pCR was predicted from relative difference (EX1 - EX2)/EX1 of Dmax and both PK parameters in the WP group and only for Ve in the TNBC group. No PK parameter could predict response for ER+/HER-. ROC comparison between WP and breast cancer groups showed higher but not statistically significant values for TNBC for the prediction of pCR Quantitative DCE-MRI can better predict pCR after neoadjuvant treatment for TNBC but not for the ER+/HER2- group. (orig.)

  8. 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.

  9. The value of metabolic imaging to predict tumour response after chemoradiation in locally advanced rectal cancer

    Directory of Open Access Journals (Sweden)

    Gómez-Río Manuel

    2010-12-01

    Full Text Available Abstract Background We aim to investigate the possibility of using 18F-positron emission tomography/computer tomography (PET-CT to predict the histopathologic response in locally advanced rectal cancer (LARC treated with preoperative chemoradiation (CRT. Methods The study included 50 patients with LARC treated with preoperative CRT. All patients were evaluated by PET-CT before and after CRT, and results were compared to histopathologic response quantified by tumour regression grade (patients with TRG 1-2 being defined as responders and patients with grade 3-5 as non-responders. Furthermore, the predictive value of metabolic imaging for pathologic complete response (ypCR was investigated. Results Responders and non-responders showed statistically significant differences according to Mandard's criteria for maximum standardized uptake value (SUVmax before and after CRT with a specificity of 76,6% and a positive predictive value of 66,7%. Furthermore, SUVmax values after CRT were able to differentiate patients with ypCR with a sensitivity of 63% and a specificity of 74,4% (positive predictive value 41,2% and negative predictive value 87,9%; This rather low sensitivity and specificity determined that PET-CT was only able to distinguish 7 cases of ypCR from a total of 11 patients. Conclusions We conclude that 18-F PET-CT performed five to seven weeks after the end of CRT can visualise functional tumour response in LARC. In contrast, metabolic imaging with 18-F PET-CT is not able to predict patients with ypCR accurately.

  10. The value of metabolic imaging to predict tumour response after chemoradiation in locally advanced rectal cancer

    International Nuclear Information System (INIS)

    We aim to investigate the possibility of using 18F-positron emission tomography/computer tomography (PET-CT) to predict the histopathologic response in locally advanced rectal cancer (LARC) treated with preoperative chemoradiation (CRT). The study included 50 patients with LARC treated with preoperative CRT. All patients were evaluated by PET-CT before and after CRT, and results were compared to histopathologic response quantified by tumour regression grade (patients with TRG 1-2 being defined as responders and patients with grade 3-5 as non-responders). Furthermore, the predictive value of metabolic imaging for pathologic complete response (ypCR) was investigated. Responders and non-responders showed statistically significant differences according to Mandard's criteria for maximum standardized uptake value (SUVmax) before and after CRT with a specificity of 76,6% and a positive predictive value of 66,7%. Furthermore, SUVmax values after CRT were able to differentiate patients with ypCR with a sensitivity of 63% and a specificity of 74,4% (positive predictive value 41,2% and negative predictive value 87,9%); This rather low sensitivity and specificity determined that PET-CT was only able to distinguish 7 cases of ypCR from a total of 11 patients. We conclude that 18-F PET-CT performed five to seven weeks after the end of CRT can visualise functional tumour response in LARC. In contrast, metabolic imaging with 18-F PET-CT is not able to predict patients with ypCR accurately

  11. Breast-conserving surgery after neoadjuvant chemotherapy in patients with locally advanced cancer. Preliminary results

    OpenAIRE

    VERGINE, M.; SCIPIONI, P.; GARRITANO, S.; COLANGELO, M.; Di Paolo, A; LIVADOTI, G.; MATURO, A.; Monti, M

    2013-01-01

    Neoadjuvant chemotherapy (NACT) in locally advanced breast tumors may allow an adequate control of the disease impossible with surgery alone. Moreover, NACT increases the chance of breast-conserving surgery. Between 2008 and 2012, we treated with NACT 83 patients with locally advanced breast cancer. We report the preliminary results evaluating the impact of NACT on the type of surgery.

  12. The determination of selenium concentration in blood and tumour tissues of breast cancer patients in Syria using instrumental neutron activation analysis

    International Nuclear Information System (INIS)

    Relationship of selenium concentration in blood components and tumour tissues of breast cancer patients and healthy volunteers (control), in Syria was investigated, using instrumental neutron activation analysis (INAA). Red blood cells and serum selenium concentrations were determined in 50 healthy volunteers aged 25-70 years and 70 breast cancer patients aged 25-84 years. Selenium levels were also measured in malignant and adjacent normal tissues from breast cancer patients. The accuracy of the analysis was evaluated by co-analyses of international reference materials. The results showed that selenium concentration in serum and RBC was significantly lower among breast cancer patients compared to healthy volunteers (P < 0.001). The results also showed that the selenium concentration was significantly higher in the cancer tissues compared to adjacent normal tissues (P < 0.001). There is a good indication for selenium deviation in blood and malignant tissue of breast cancer patients compared to that of healthy volunteers. (author)

  13. Wide-field optical coherence elastography for intraoperative assessment of tumour margins in breast cancer (Conference Presentation)

    Science.gov (United States)

    Allen, Wes M.; Chin, Lixin; Sampson, David D.; Kennedy, Brendan F.

    2016-03-01

    Incomplete excision of tumour margins is a major issue in breast-conserving surgery. Currently 20 - 60% of cases require a second surgical procedure required as a result of cancer recurrence. A number of techniques have been proposed to assess margin status, including frozen section analysis and imprint cytology. However, the recurrence rate after using these techniques remains very high. Over the last several years, our group has been developing optical coherence elastography (OCE) as a tool for the intraoperative assessment of tumour margins in breast cancer. We have reported a feasibility study on 65 ex vivo samples from patients undergoing mastectomy or wide local excision demonstrates the potential of OCE in differentiating benign from malignant tissue. In this study, malignant tissue was readily distinguished from surrounding relative tissue by a distinctive heterogeneous pattern in micro-elastograms. To date the largest field of view for a micro-elastogram is 20 x 20mm, however, lumpectomy samples are typically ~50 x 50 x 30mm. For OCE to progress as a useful clinical tool, elastograms must be acquired over larger areas to allow a greater portion of the surface area of lumpectomies to be assessed. Here, we propose a wide-field OCE scanner that utilizes a piezoelectric transducer with an internal diameter of 65mm. In this approach partially overlapped elastograms are stitched together forming a mosaic with overall dimensions of 50 x 50mm in a total acquisition time of 15 - 30 minutes. We present results using this approach on both tissue-mimicking phantoms and tissue, and discuss prospects for shorter acquisitions times.

  14. The rationale for combined chemo/immunotherapy using a Toll-like receptor 3 (TLR3) agonist and tumour-derived exosomes in advanced ovarian cancer.

    Science.gov (United States)

    Adams, M; Navabi, H; Croston, D; Coleman, S; Tabi, Z; Clayton, A; Jasani, B; Mason, M D

    2005-03-18

    A clinical trial employing an immunotherapeutic approach based on the use of a Toll-like receptor 3 (TLR3) agonist and tumour-derived exosomes carrying tumour-associated antigens is planned in advanced ovarian cancer in conjunction with conventional first line chemotherapy. Most patients with ovarian cancer present with advanced disease and despite high initial response rate to chemotherapy the majority will relapse within 2 years with poor overall survival. Tumour antigen-specific T cells are naturally occurring in ovarian cancer patients and T cell infiltration of the tumour is highly prognostic. Novel immunotherapy to expand and activate tumour antigen-specific T cells combined with adjuvant treatment to overcome tumour-induced immunosuppression is considered to be therapeutically beneficial. The rationale for adopting such a combined approach is discussed here. PMID:15755631

  15. Tumour screening by means of tomography methods

    International Nuclear Information System (INIS)

    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

  16. A positive contrast, tri-modality tissue marker for breast tumour localization

    International Nuclear Information System (INIS)

    A new interstitial breast localization marker is proposed which exhibits positive contrast in T1-weighted MRI, ultrasound and x-ray mammography. Unlike previous markers which provide MRI contrast on the basis of a susceptibility-induced signal void, this marker provides a clear positive contrast without any loss of signal or spatial distortion. The marker is composed of 400 μm diameter copper microspheres suspended in a Gd-DTPA-doped gel matrix. Optimal contrast in T1-weighted spoiled gradient recalled MRI was found to occur with the addition of 10 mM Gd-DTPA. Ultrasound contrast was generated on the basis of scattering from the copper microspheres. X-ray contrast was provided by the high x-ray attenuation properties of the copper microspheres. The study demonstrates potential suitability of the marker for use as a breast localization marker based on ex vivo studies of chicken breast. (note)

  17. Giant nodular pseudoangiomatous stromal hyperplasia (PASH) of the breast presenting as a rapidly growing tumour.

    Science.gov (United States)

    Mezzabotta, Maurizio; Riccardi, Silvia; Bonvini, Simona; Declich, Paolo; Tavani, Enrico; Morandi, Eugenio

    2009-01-01

    Pseudoangiomatous stromal hyperplasia (PASH) is often a microscopic incidental finding in breast biopsies performed for benign or malignant diseases. In rare cases, it presents as a localised breast mass. Since Vuitch et al first described this condition in 1986, only 109 cases of PASH presenting as a palpable or mammographically detectable mass have been documented. PASH is characterised by a dense, collagenous proliferation of mammary stroma, forming inter-anastomosing capillary-like spaces. It is important to distinguish this benign lesion from a low-grade angiosarcoma. Here we describe the clinical, radiological and histological features of a very unusual case of PASH that presented as a rapidly growing breast lesion in a 37-year old woman. PMID:19694241

  18. Tumour response after hyperthermic isolated limb perfusion for locally advanced melanoma

    DEFF Research Database (Denmark)

    Paulsen, Ida Felbo; Chakera, A H; Drejøe, Jennifer Berg; Klyver, Helle; Dahlstrøm, Karin; Oturai, Peter Sandor; Mortensen, Jann; Hesse, Birger; Schmidt, Grethe; Drzewiecki, Krzysztof

    2014-01-01

    INTRODUCTION: The aim was to describe tumour response, complications, recurrence and survival after hyperthermic isolated limb perfusion (ILP) with melphalan or melphalan in combination with tumour necrosis factor-alpha in patients with melanoma metastases confined to an extremity. MATERIAL AND...

  19. Combined radiotherapy with cis- or carboplatin in advanced head and neck tumours

    International Nuclear Information System (INIS)

    This report reviews the treatment results of 111 patients with stage T3-4, N0-3, M0, biopsy proven squamous cell carcinoma of the oropharynx and oral cavity. All patients were treated by primary irradiation with 1.8 to 2 Gy per day for five days a week up to a target volume dose of 39,6 or 40 Gy. Simultaneously 20 mg/m2 cisplatin was given under hyperhydration and mannitol diuresis on days 1 to 5. In case of partial tumour regression radiotherapy was continued up to 70 Gy with another course of cisplatin. In case of minor response surgery was interposed followed by subsequent irradiation with 30 Gy and a second course of cisplatin. 67% of the patients showed an initial complete tumour involution and 27% a partial response. The five year actuarial survival rate with a minimum follow-up of two years is 47,6%. More than 96% of the long term survivors showed a complete response after the end of treatment. Carboplatin (CBDCA) is a second generation platinum analogon and has shown comparable antitumour activity but less nephro- and neurotoxicity than cisplatin in head and neck cancer. In order to determine the feasibility and efficacy of simultaneous application of CBDCA and radiotherapy a phase I-II study is going on. Patients with advanced squamous carcinoma of the head and neck were separated into three groups which received 60 mg/m2, 70 mg/m2 and 80 mg/m2 CBDCA from days 1 to 5 and 28 to 32. Radiotherapy was administrated up to a target absorbed dose of 70 Gy, 5x2 Gy/week in shrinking field technique. The group which received 80 mg/m2 CBDCA reached the myelotoxicity limit so that subsequent patients were treated with 70 mg/m2. Among 30 patients who completed the treatment, 22 showed a complete (CR) and eight a partial remission (PR). (orig./MG)

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

    DEFF Research Database (Denmark)

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

    2013-01-01

    The Tn antigen (GalNAc alpha-O-Ser/Thr) as defined by the binding of the lectin, helix pomatia agglutinin (HPA) or anti-Tn monoclonal antibodies, is known to be exposed in a majority of cancers, and it has also been shown to correlate positively with the metastatic capacity in breast carcinoma. T...

  1. Locally advanced non inflammatory breast cancer treated by combined chemotherapy and preoperative irradiation: updated results in a series of 120 patients

    International Nuclear Information System (INIS)

    Purpose. - To evaluate our updated data concerning survival and locoregional control in a study of locally advanced non inflammatory breast cancer after primary chemotherapy followed by external preoperative irradiation. Patients and methods. - Between 1982 and 1998, 120 patients (75 stage IIIA, 41 stage IIIB, and 4 stage IIIC according to AJCC staging system 2002) were consecutively treated by four courses of induction chemotherapy with anthracycline-containing combinations followed by preoperative irradiation (45 Gy to the breast and nodal areas) and a fifth course of chemotherapy. Three different locoregional approaches were proposed, depending on tumour characteristics and tumour response. After completion of local therapy, all patients received a sixth course of chemotherapy and a maintenance adjuvant chemotherapy regimen without anthracycline. The median follow-up from the beginning of treatment was 140 months. Results. - Mastectomy and axillary dissection were performed in 49 patients (with residual tumour larger than 3 cm in diameter or located behind the nipple or with bifocal tumour), and conservative treatment in 71 patients (39 achieved clinical complete response or partial response >90% and received additional radiation boost to initial tumour bed; 32 had residual mass ≤3 cm in diameter and were treated by wide excision and axillary dissection followed by a boost to the excision site). Ten-year actuarial local failure rate was 13% after irradiation alone, 23% after wide excision and irradiation, and 4% after mastectomy (p =0.1). After multivariate analysis, possibility of breast-conserving therapy was related to initial tumour size (<6 vs. ≥6 cm in diameter, p =0.002). Ten-year overall metastatic disease-free survival rate was 61%. After multivariate analysis, metastatic disease-free survival rates were significantly influenced by clinical stage (stage IIIA-B vs. IIIC, p =0.0003), N-stage (N0 vs. N1-2a, and 3c, p = 0.017), initial tumour size (<6

  2. TIMP-1 and responsiveness to gemcitabine in advanced breast cancer

    DEFF Research Database (Denmark)

    Jørgensen, Charlotte Levin Tykjær; Bjerre, Christina Annette; Ejlertsen, Bent Laursen;

    2014-01-01

    status was performed retrospectively on primary tumor whole-tissue sections by immunohistochemistry and tumor samples were considered positive if epithelial breast cancer cells were stained by the anti-TIMP-1 monoclonal antibody VT7. Time to progression (TTP) was the primary endpoint. Overall survival...... classified as cancer cell TIMP-1 positive. No significant difference for TTP between TIMP-1 positive versus TIMP-1 negative patients was observed in multivariate analysis, and RR did not differ according to TIMP-1 status. However, patients with TIMP-1 positive tumors had a significant reduction in OS events...... receiving GD. CONCLUSIONS: TIMP-1 status was an independent prognostic factor for OS but not TTP in patients with advanced breast cancer receiving either D or GD. There was no statistically significant interaction between TIMP-1 status and treatment, but a trend towards an incremental OS from the addition...

  3. A gene signature of loss of oestrogen receptor (ER) function and oxidative stress links ER-positive breast tumours with an absent progesterone receptor and a poor prognosis

    OpenAIRE

    Neven, Patrick; Van Gorp, Toon; Deraedt, Karen

    2008-01-01

    Prognostic gene signatures like the wound and hypoxia signature differ by assumptions of cellular growth. Although gene signatures show little overlap, they also track within the group of luminal breast tumours those with a high proliferation and poor prognosis. Oxidative stress is another assumption of cellular growth. It affects several pathological conditions through its influence on the regulation of protein kinases and signal transduction pathways. A comprehensive set of 62 core genes fr...

  4. Treatment of locally advanced/locally recurrent breast cancer and inflammatory breast cancer

    Energy Technology Data Exchange (ETDEWEB)

    Murakami, Masao [Tenri Hospital, Nara (Japan)

    2000-10-01

    This paper summarizes the treatment of locally advanced breast cancer, inflammatory breast cancer, and locally recurrent breast cancer. A multidisciplinary approach considering subclinical distant metastases is needed to treat these types of breast cancer. Subclinical distant metastasis is observed in about 80% of case of locally advanced cancer, and treatment of subclinical distant metastases, e.g., by endocrinotherapy and chemotherapy, is therefore essential to improving the prognosis. The standard therapy for unresectable locally advanced breast cancer consists of induction chemotherapy with anthracyclines and local treatment with mastectomy or irradiation. Previous reports have stated that induction chemotherapy was effective in 60-80% of the primary lesions or lymph node metastasis, and the CR rates were in the 10-20% range. Combination therapy with induction chemotherapy clearly improved the outcome over local treatment alone. The usual irradiation dose is 50 to 60 Gy/5 to 7 weeks to the whole breast or the thoracic wall. Boost irradiation at a dose of 10 to 25 Gy is performed in unresectable cases. The boost irradiation dose to the lymph node area is usually 45 to 50 Gy/5 to 6 weeks in cases without gross lesions and 10 to 15 Gy in cases with gross lesions. Combination therapy consisting of conservative pectoral mastectomy and postoperative adjuvant chemo- endocrino-therapy (i.e., adjuvant therapy) has become the standard regimen for treating resectable locally advanced breast cancer, because it significantly improves the recurrence rate and survival rate compared to local treatment alone. Some clinical have studies indicated that neoadjuvant therapy (i.e., induction chemotherapy + surgery/radiation therapy) is comparable or superior to adjuvant therapy in terms of improving the prognosis. However, the efficacy and most appropriate method of breast-conserving therapy after induction chemotherapy are still unclear. More clinical trials are needed. It has been

  5. Biochemical signatures of in vitro radiation response in human lung, breast and prostate tumour cells observed with Raman spectroscopy

    Energy Technology Data Exchange (ETDEWEB)

    Matthews, Q; Jirasek, A [Department of Physics and Astronomy, University of Victoria, Victoria BC V8W 3P6 (Canada); Lum, J J [Deeley Research Centre, BC Cancer Agency, Vancouver Island Centre, Victoria BC V8R 6V5 (Canada); Brolo, A G, E-mail: qmatthew@uvic.ca, E-mail: jirasek@uvic.ca [Department of Chemistry, University of Victoria, Victoria BC V8W 3V6 (Canada)

    2011-11-07

    This work applies noninvasive single-cell Raman spectroscopy (RS) and principal component analysis (PCA) to analyze and correlate radiation-induced biochemical changes in a panel of human tumour cell lines that vary by tissue of origin, p53 status and intrinsic radiosensitivity. Six human tumour cell lines, derived from prostate (DU145, PC3 and LNCaP), breast (MDA-MB-231 and MCF7) and lung (H460), were irradiated in vitro with single fractions (15, 30 or 50 Gy) of 6 MV photons. Remaining live cells were harvested for RS analysis at 0, 24, 48 and 72 h post-irradiation, along with unirradiated controls. Single-cell Raman spectra were acquired from 20 cells per sample utilizing a 785 nm excitation laser. All spectra (200 per cell line) were individually post-processed using established methods and the total data set for each cell line was analyzed with PCA using standard algorithms. One radiation-induced PCA component was detected for each cell line by identification of statistically significant changes in the PCA score distributions for irradiated samples, as compared to unirradiated samples, in the first 24-72 h post-irradiation. These RS response signatures arise from radiation-induced changes in cellular concentrations of aromatic amino acids, conformational protein structures and certain nucleic acid and lipid functional groups. Correlation analysis between the radiation-induced PCA components separates the cell lines into three distinct RS response categories: R1 (H460 and MCF7), R2 (MDA-MB-231 and PC3) and R3 (DU145 and LNCaP). These RS categories partially segregate according to radiosensitivity, as the R1 and R2 cell lines are radioresistant (SF{sub 2} > 0.6) and the R3 cell lines are radiosensitive (SF{sub 2} < 0.5). The R1 and R2 cell lines further segregate according to p53 gene status, corroborated by cell cycle analysis post-irradiation. Potential radiation-induced biochemical response mechanisms underlying our RS observations are proposed, such as (1

  6. Biochemical signatures of in vitro radiation response in human lung, breast and prostate tumour cells observed with Raman spectroscopy

    Science.gov (United States)

    Matthews, Q.; Jirasek, A.; Lum, J. J.; Brolo, A. G.

    2011-11-01

    This work applies noninvasive single-cell Raman spectroscopy (RS) and principal component analysis (PCA) to analyze and correlate radiation-induced biochemical changes in a panel of human tumour cell lines that vary by tissue of origin, p53 status and intrinsic radiosensitivity. Six human tumour cell lines, derived from prostate (DU145, PC3 and LNCaP), breast (MDA-MB-231 and MCF7) and lung (H460), were irradiated in vitro with single fractions (15, 30 or 50 Gy) of 6 MV photons. Remaining live cells were harvested for RS analysis at 0, 24, 48 and 72 h post-irradiation, along with unirradiated controls. Single-cell Raman spectra were acquired from 20 cells per sample utilizing a 785 nm excitation laser. All spectra (200 per cell line) were individually post-processed using established methods and the total data set for each cell line was analyzed with PCA using standard algorithms. One radiation-induced PCA component was detected for each cell line by identification of statistically significant changes in the PCA score distributions for irradiated samples, as compared to unirradiated samples, in the first 24-72 h post-irradiation. These RS response signatures arise from radiation-induced changes in cellular concentrations of aromatic amino acids, conformational protein structures and certain nucleic acid and lipid functional groups. Correlation analysis between the radiation-induced PCA components separates the cell lines into three distinct RS response categories: R1 (H460 and MCF7), R2 (MDA-MB-231 and PC3) and R3 (DU145 and LNCaP). These RS categories partially segregate according to radiosensitivity, as the R1 and R2 cell lines are radioresistant (SF2 > 0.6) and the R3 cell lines are radiosensitive (SF2 < 0.5). The R1 and R2 cell lines further segregate according to p53 gene status, corroborated by cell cycle analysis post-irradiation. Potential radiation-induced biochemical response mechanisms underlying our RS observations are proposed, such as (1) the regulated

  7. Radioimmunoassay of serum creatine kinase-BB as a tumour marker in breast cancer

    International Nuclear Information System (INIS)

    Brain type creatine kinase-BB (CPK-BB) was measured by radioimmunoassay in the serum of 113 women with breast cancer and 354 female controls. 80% of women with metastatic breast cancer had levels above 3 ng/ml (control range 0.5-3.7 ng/ml); the highest level was 23 ng/ml. 60% of women with local disease but no evidence of distant metastases showed levels above 3 ng/ml, the highest being 9.0 ng/ml. Of women who had presented with stage I, II, or III disease and postoperatively had no evidence of persistent disease 30% had levels above 3 ng/ml. Serial measurements in 31 patients indicated that the serum CPK-BB correlated with clinical response to treatment. (author)

  8. Postmastectomy Radiotherapy for Locally Advanced Breast Cancer Receiving Neoadjuvant Chemotherapy

    OpenAIRE

    Icro Meattini; Sara Cecchini; Vanessa Di Cataldo; Calogero Saieva; Giulio Francolini; Vieri Scotti; Pierluigi Bonomo; Monica Mangoni; Daniela Greto; Jacopo Nori; Lorenzo Orzalesi; Donato Casella; Roberta Simoncini; Massimiliano Fambrini; Simonetta Bianchi

    2014-01-01

    Neoadjuvant chemotherapy (NAC) is widely used in locally advanced breast cancer (BC) treatment. The role of postmastectomy radiotherapy (PMRT) after NAC is strongly debated. The aim of our analysis was to identify major prognostic factors in a single-center series, with emphasis on PMRT. From 1997 to 2011, 170 patients were treated with NAC and mastectomy at our center; 98 cases (57.6%) underwent PMRT and 72 cases (42.4%) did not receive radiation. At a median follow-up period of 7.7 years (r...

  9. In Silico Modelling of Treatment-Induced Tumour Cell Kill: Developments and Advances

    OpenAIRE

    Marcu, Loredana G.; Harriss-Phillips, Wendy M.

    2012-01-01

    Mathematical and stochastic computer (in silico) models of tumour growth and treatment response of the past and current eras are presented, outlining the aims of the models, model methodology, the key parameters used to describe the tumour system, and treatment modality applied, as well as reported outcomes from simulations. Fractionated radiotherapy, chemotherapy, and combined therapies are reviewed, providing a comprehensive overview of the modelling literature for current modellers and rad...

  10. Advance care planning in patients with brain tumours: A prospective cohort study

    Directory of Open Access Journals (Sweden)

    Krystal Song

    2015-08-01

    Full Text Available Objectives: To assess and understand the awareness and experience of brain tumour (BT patients in discussing Advance Care Planning (ACP, to identify main symptoms experienced, physical and functional status perceived quality of life, and level of coping. Methods: A prospective cohort study with an initial open-ended questionnaire followed by semi-structured interview questions regarding ACP with 18 patients diagnosed with BT (WHO Grade I-IV, metastatic BT in hospital and community. Standardized assessments measured coping strategies, and quality of life (QoL. Interview transcripts regarding ACP discussions were analyzed, coded and interpreted using qualitative analytic techniques for thematic analyses. Results: Participants' mean age was 51 years (range 22-65 years, female (61%; median time since BT diagnosis was 1.5 years and just over half (56% had glioblastoma multiforme (GBM. Fatigue was the most common symptom reported by 83% of participants. Overall, participants indicated good QoL and used more problem-focused coping strategies including ‘acceptance’ and ‘positive reframing’. Thematic analyses indicated that participants had limited awareness and understanding of ACP, variable views on appropriate timing of ACP discussions and change of decisions over illness trajectory. Most felt able to discuss ACP and preferred dedicated sessions by a trained health professional. Conclusion: This study highlights the importance of providing timely information regarding ACP to BT patients during the course of their disease. Established ACP discussions have an important role in enhancing patient autonomy and to guide delivery of end-of-life care. The demonstrated low uptake of ACP in this pilot study shows need for improved awareness in clinical practice for timely ACP discussions and multifaceted interventions system-wide in implementing ACP

  11. Management of locally advanced breast cancer: Evolution and current practice

    Directory of Open Access Journals (Sweden)

    Rustogi Ashish

    2005-01-01

    Full Text Available Locally advanced breast cancer (LABC accounts for a sizeable number (30-60% of breast cancer cases and is a common clinical scenario in developing countries. The treatment of LABC has evolved from single modality treatment, consisting of radical mutilating surgery or higher doses of radiotherapy in inoperable disease to multimodality management, which along with the above two included systemic therapy. Neoadjuvant chemotherapy (NACT has made a tremendous impact on the management of LABC. NACT was initiated to institute systemic therapy upfront at the earliest in this group of patients with a high risk of micrometastasis burden. While NACT did not yield a survival advantage, it has however made breast conservation possible in selected group of cases. Large number of studies and many randomised trials have been done in women with LABC in order to improve the therapeutic decisions and also the local control and survival. With this background we have reviewed various treatment options in patients with LABC which should possibly help in guiding the clinicians for optimal management of LABC.

  12. 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. PMID:26848098

  13. Tumour Delineation using Statistical Properties of The Breast US Images and Vector Quantization based Clustering Algorithms

    Directory of Open Access Journals (Sweden)

    H. B. Kekre

    2013-09-01

    Full Text Available Breast cancer is most common and leading cause of death among women. With improvement in the imaging modalities it is possible to diagnose the cancer at an early stage moreover treatment at an early stage reduces the mortality rate. B-mode ultrasound (US imaging is very illustrious and reliable technique in early detection of masses in the breast. Though it is complimentary to the mammography, dense breast tissues can be examined more efficiently and detects the small nodules that are usually not observed in mammography. Segmentation of US images gives the clear understanding of nature and growth of the tumor. But some inherent artifact of US images makes this process difficult and computationally inefficient. Many methods are discussed in the literature for US image segmentation, each method has its pros and cons. In this paper, initially region merging based watershed and marker-controlled watershed transforms are discussed and implemented. In the subsequent sections we proposed a method for segmentation, based on clustering. Proposed method consists of three stages, in first stage probability images and its equalized histogram images are obtained from the original US images without any preprocessing. In the next stage, we used VQ based clustering technique with LBG, KPE and KEVR codebook generation algorithm followed by sequential cluster merging. Last stage is the post processing, where we removed unwanted regions from the selected cluster image by labeling the connected components and moreover used morphological operation for closing the holes in the final segmented image. Finally, results by our method are compared with initially discussed methods.

  14. Breast cancer: Postoperative irradiation and management of locally advanced disease

    International Nuclear Information System (INIS)

    Purpose/Objective: This course will review current indications for postoperative irradiation, present a videotape demonstration of a simulation technique for comprehensive chest wall/nodal irradiation, and discuss multimodality approaches to the difficult problem of locally advanced breast cancer. As part of an expanding role for the radiation oncologist in the treatment of all stages of breast cancer, recent data has inspired a reevaluation of chest wall and nodal irradiation following mastectomy. A decade ago, adjuvant irradiation was considered by many oncologists to be of no survival advantage or perhaps even harmful. Studies leading to this conclusion will be reviewed with special attention to the inadequacies and flawed constructs which biased these studies against adjuvant chest wall/nodal irradiation. The Fischer hypothesis or 'new paradigm' will be challenged. Can improvement in local control result in improved survival? If the goal of treatment is simply to reduce local-regional recurrence, a three-field technique covering the chest wall and supraclavicular nodes may suffice. But if the goal is an improvement in survival based on the treatment of all locoregional sites which may not be sterilized by chemotherapy and mastectomy, a more complex set of fields is required. Based on this premise, we designed a 5-field technique of comprehensive chest wall and nodal irradiation. Simulation of these fields will be demonstrated on videotape. Treatment strategies for both non-inflammatory and inflammatory non-metastatic breast cancer will be presented. Current recommendations include various combinations of chemohormonotherapy, radiation therapy, and mastectomy, but controversies abound regarding the proper sequencing of these modalities, whether breast conservation therapy can be offered to patients who have a dramatic response to systemic therapy, and whether or not any one of these treatment modalities can be dropped under specific clinical scenarios

  15. Breast cancer: Postoperative irradiation and management of locally advanced disease

    International Nuclear Information System (INIS)

    Purpose/Objective: This course will review current indications for postoperative irradiation, present a videotape demonstration of a simulation technique for comprehensive chest wall/nodal irradiation, and discuss multimodality approaches to the difficult problem of locally advanced breast cancer. As part of an expanding role for the radiation oncologist in the treatment of all stages of breast cancer, recent data has inspired a reevaluation of chest wall and nodal irradiation following mastectomy. A decade ago, adjuvant irradiation was considered by many oncologists to be of no survival advantage or perhaps even harmful. Studies leading to this conclusion will be reviewed with special attention to the inadequacies and flawed constructs which biased these studies against adjuvant chest wall/nodal irradiation. The Fischer hypothesis or 'new paradigm' will be challenged. Can improvement in local control result in improved survival? If the goal of treatment is simply to reduce local-regional recurrence, a three-field technique covering the chest wall and supraclavicular nodes may suffice. But if the goal is an improvement in survival based on the treatment of all locoregional sites which may not be sterilized by chemotherapy and mastectomy, a more complex set of fields is required. Based on this premise, we designed a 5-field technique of comprehensive chest wall and nodal irradiation. Simulation of these fields will be demonstrated on videotape. Treatment strategies for both non-inflammatory and inflammatory non-metastatic breast cancer will be presented. Current recommendations include various combinations of chemohormonotherapy, radiation therapy, and mastectomy, but Controversies abound regarding the proper sequencing of these modalities, whether breast conservation therapy can be offered to patients who have a dramatic response to systemic therapy, and whether or not any one of these treatment modalities can be dropped under specific clinical scenarios

  16. Bilateral orbital tumour as the presentation of mammographically occult breast cancer

    Energy Technology Data Exchange (ETDEWEB)

    Lell, M.; Schulz-Wendtland, R.; Bautz, W.A. [Institute of Radiology, University of Erlangen-Nuernberg, Maximiliansplatz 1, 91504, Erlangen (Germany); Hafner, A. [Department of Ophthalmology, University of Erlangen-Nuernberg, Maximiliansplatz 1, 91504, Erlangen (Germany); Magener, A. [Institute of Pathology, University of Erlangen-Nuernberg, Maximiliansplatz 1, 91504, Erlangen (Germany); Tomandl, B.F. [Department of Neuroradiology, University of Erlangen-Nuernberg, Maximiliansplatz 1, 91504, Erlangen (Germany)

    2004-08-01

    We report a rare case of bilateral orbital metastases as the presentation in a 63-year-old woman. Biopsy of a diffusely infiltrated medial rectus muscle suggested metastatic adenocarcinoma. Investigation revealed a palpable mass of the right breast not shown on mammography or sonography. Invasive lobular carcinoma was found at core-needle biopsy with histological features identical to those of the orbital lesion. Metastases to the extraocular muscles are uncommon, particularly as the initial abnormality in the absence of disseminated disease. (orig.)

  17. A comparison among HER2, TP53, PAI-1, angiogenesis, and proliferation activity as prognostic variables in tumours from 408 patients diagnosed with early breast cancer

    DEFF Research Database (Denmark)

    Offersen, Birgitte Vrou; Alsner, Jan; Olsen, Karen Ege;

    2008-01-01

    BACKGROUND: The prognostic potential of HER2, TP53 mutations, PAI-1 protein levels, angiogenesis and proliferation were investigated in tumours from 408 patients with early breast cancer followed >10 years. One hundred and sixty seven patients (41%) died from breast cancer. MATERIALS AND METHODS...

  18. Outcome of peptide receptor radionuclide therapy with 177Lu-octreotate in advanced grade 1/2 pancreatic neuroendocrine tumours

    International Nuclear Information System (INIS)

    The clinical benefit of peptide receptor radionuclide therapy (PRRT) in patients with pancreatic neuroendocrine tumours (pNET) has not yet been well described and defined in its full extent due to limited data in this tumour subgroup. This study was intended to obtain robust, comparative data on the outcome and toxicity of standardized PRRT with 177Lu-octreotate in a well-characterized population of patients with advanced pNET of grade 1/2 (G1/2). We retrospectively analysed a cohort of 68 pNET patients with inoperable metastatic disease consecutively treated with 177Lu-octreotate (four intended cycles at 3-monthly intervals; mean activity per cycle 8.0 GBq). Of these 68 patients, 46 (67.6 %) had documented morphological tumour progression during the 12 months before initiation of treatment, and PRRT was the first-line systemic therapy in 35 patients (51.5 %). Response was evaluated according to modified Southwest Oncology Group (SWOG) criteria and additionally with Response Criteria in Solid Tumors (RECIST) 1.1. Survival was analysed using Kaplan-Meier curves and Cox proportional hazards model for univariate and multivariate analyses. Toxicity was assessed by standard follow-up laboratory work-up including blood count, and liver and renal function, supplemented with serial 99mTc-DTPA clearance measurements. The median follow-up period was 58 months (range 4 - 112). Reversible haematotoxicity (grade 3 or more) occurred in four patients (5.9 %). No significant nephrotoxicity (grade 3 or more) was observed. Treatment responses (SWOG criteria) consisted of a partial response in 41 patients (60.3 %), a minor response in 8 (11.8 %), stable disease in 9 (13.2 %), and progressive disease in 10 (14.7 %). Median progression-free survival (PFS) and overall survival (OS) were 34 (95 % CI 26 - 42) and 53 months (95 % CI 46 - 60), respectively. A G1 proliferation status was associated with longer PFS (p = 0.04) and OS (p = 0.044) in the multivariate analysis. Variables linked

  19. A Serum Protein Profile Predictive of the Resistance to Neoadjuvant Chemotherapy in Advanced Breast Cancers*

    OpenAIRE

    Hyung, Seok-Won; Lee, Min Young; Yu, Jong-Han; Shin, Byunghee; Jung, Hee-Jung; Park, Jong-Moon; Han, Wonshik; Lee, Kyung-min; Moon, Hyeong-Gon; Zhang, Hui; Aebersold, Ruedi; Hwang, Daehee; Lee, Sang-Won; Yu, Myeong-Hee; Noh, Dong-Young

    2011-01-01

    Prediction of the responses to neoadjuvant chemotherapy (NACT) can improve the treatment of patients with advanced breast cancer. Genes and proteins predictive of chemoresistance have been extensively studied in breast cancer tissues. However, noninvasive serum biomarkers capable of such prediction have been rarely exploited. Here, we performed profiling of N-glycosylated proteins in serum from fifteen advanced breast cancer patients (ten patients sensitive to and five patients resistant to N...

  20. Clofarabine, a novel adenosine analogue, reactivates DNA methylation-silenced tumour suppressor genes and inhibits cell growth in breast cancer cells.

    Science.gov (United States)

    Lubecka-Pietruszewska, Katarzyna; Kaufman-Szymczyk, Agnieszka; Stefanska, Barbara; Cebula-Obrzut, Barbara; Smolewski, Piotr; Fabianowska-Majewska, Krystyna

    2014-01-15

    Clofarabine (2-chloro-2'-fluoro-2'-deoxyarabinosyladenine, ClF) is a second-generation 2'-deoxyadenosine analogue that is structurally related to cladribine (2-chloro-2'-deoxyadenosine, 2CdA) and fludarabine (9-beta-d-arabinosyl-2-fluoroadenine, F-ara-A). It demonstrates potent antitumour activity at much lower doses than parent compounds with high therapeutic efficacy in paediatric blood cancers. Our previous studies in breast cancer cells indicate that 2CdA and F-ara-A are involved in epigenetic regulation of gene transcription. We therefore investigated whether ClF influences methylation and expression of selected tumour suppressor genes, such as adenomatous polyposis coli (APC), phosphatase and tensin homologue (PTEN), and retinoic acid receptor beta 2 (RARbeta2), as well as expression of p53, p21 and DNA methyltransferase 1 (DNMT1) in MCF-7 and MDA-MB-231 breast cancer cell lines with different invasive potential. Promoter methylation and gene expression were estimated using methylation-sensitive restriction analysis (MSRA) and real-time PCR, respectively. ClF demonstrated potent growth inhibitory activity in MCF-7 and MDA-MB-231 cells after 96h treatment with IC50 determined as equal to 640nM and 50nM, respectively. In both breast cancer cell lines, ClF led to hypomethylation and up-regulation of APC, PTEN and RARbeta2 as well as increase in p21 expression. Only in non-invasive MCF-7 cells, these changes were associated with down-regulation of DNMT1. Our results provide first evidence of ClF implications in epigenetic regulation of transcriptional activity of selected tumour suppressor genes in breast cancer. It seems to be a new important element of ClF anticancer activity and may indicate its potential efficacy in epigenetic therapy of solid tumours, especially at early stages of carcinogenesis. PMID:24296317

  1. Should needle localization breast biopsy give way to the new technology; the advanced breast biopsy instrumentation.

    Science.gov (United States)

    Hawasli, A; Zonca, S; Watt, C; Rebecca, A

    2000-07-01

    Between July 1995 and June 1997, 114 consecutive women underwent 118 breast biopsies for nonpalpable lesions. A limited procedure room and local anesthesia were used in 96.5 per cent of patients. Intravenous access was not established in 95 per cent of patients. Oral diazepam was given to 51 per cent of patients. Needle localization technique was used with a success rate of 97.5 per cent and average operative time of 18 minutes. Breast carcinoma was found in 29 (24.6 per cent) biopsies. A review of 99 of the 118 mammograms showed only 45 per cent of the lesions being amenable to the new technology, the advanced breast biopsy instrumentation. Advantages of the needle localization include short operative time; supine position for the patient; easy access to control bleeding; ability to choose a cosmetic site for the skin incision; minimal tissue removal before reaching the lesion; ability to maintain a sterile field; and applicability to almost any mammographic lesion identified, whether single or multiple. Disadvantages include the need for a separate procedure to place the wire and potential of missing the lesion in 2.5 per cent, requiring additional surgery. PMID:10917475

  2. 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)

    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

  3. 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.)

  4. 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.

  5. The curability of breast cancer and the treatment of advanced disease

    International Nuclear Information System (INIS)

    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

  6. IMPACT OF SEQUENTIAL NEOADJUVANT CHEMOTHERAPY IN LOCALLY ADVANCED BREAST CANCER: A SERIES OF 10 CASES

    OpenAIRE

    Gopa; Megha; Atul,; Bindu

    2014-01-01

    Breast cancer currently is a major health problem among women worldwide accounting for around 13.7% cancer deaths, nearly 1/3rd of it being due to Locally advanced breast cancer (LABC). Despite progress achieved in diagnosis & therapy of Breast cancer, LABC remains a major clinical challenge and in efforts to increase pCR, CCR & DFS in LABC, Neoadjuvant or primary chemotherapy followed by locoregional therapy and adjuvant systemic CT is well accepted treatment strategy sin...

  7. Applicazione della classificazione National Health Service Breast Screening Pathology (NHSBSP) nella comparazione cito-istologica dei tumori mammari della cagna = NHSBSP classification use in the correlation of canine mammary tumour cytology and histopathology

    OpenAIRE

    Antuofermo, Elisabetta; Rocca, Stefano; Burrai, Giovanni; Pirino, Salvatore; Castiglia, Paolo Giuseppino; Marras, Vincenzo

    2007-01-01

    Canine mammary tumours (CMT) are the most common neoplasia in bitches. Fine needle aspiration cytology (FNAC) is a fast and inexpensive technique well-tolerated by animals. Few reports have shown how difficult cytological diagnosis of CMT is and how difficult benign or malignant tumours are to classify using FNAC. Cytological diagnosis has often been inconclusive in veterinary pathology. In the diagnosis of human breast cancer, FNAC efficacy is beyond doubt due to its high specifi...

  8. Specific efficacy of peptide receptor radionuclide therapy with 177Lu-octreotate in advanced neuroendocrine tumours of the small intestine

    International Nuclear Information System (INIS)

    Increasing evidence supports the value of peptide receptor radionuclide therapy (PRRT) in patients with metastatic neuroendocrine tumours (NET), but there are limited data on its specific efficacy in NET of small intestinal (midgut) origin. This study aims to define the benefit of PRRT with 177Lu-octreotate for this circumscribed entity derived by a uniformly treated patient cohort. A total of 61 consecutive patients with unresectable, advanced small intestinal NET G1-2 stage IV treated with 177Lu-octreotate (4 intended cycles at 3-month intervals, mean activity per cycle 7.9 GBq) were analysed. Sufficient tumour uptake on baseline receptor imaging and either documented tumour progression (n = 46) or uncontrolled symptoms (n = 15) were prerequisites for treatment. Response was evaluated according to modified Southwest Oncology Group (SWOG) criteria and additionally with Response Criteria in Solid Tumors (RECIST) 1.1. Assessment of survival was performed using Kaplan-Meier curves and Cox proportional hazards model for uni- and multivariate analyses. Toxicity was assessed according to standardized follow-up laboratory work-up including blood counts, liver and renal function, supplemented with serial 99mTc-diethylenetriaminepentaacetic acid (DTPA) clearance measurements. The median follow-up period was 62 months. Reversible haematotoxicity (≥ grade 3) occurred in five patients (8.2 %). No significant nephrotoxicity (≥ grade 3) was observed. Treatment response according to modified SWOG criteria consisted of partial response in 8 (13.1 %), minor response in 19 (31.1 %), stable disease in 29 (47.5 %) and progressive disease in 5 (8.2 %) patients. The disease control rate was 91.8 %. Median progression-free survival (PFS) and overall survival (OS) was 33 [95 % confidence interval (CI) 25-41] and 61 months (95 % CI NA), respectively. Objective response was associated with longer survival (p = 0.005). Independent predictors of shorter PFS were functionality [hazard

  9. Absence of transforming growth factor-beta type II receptor is associated with poorer prognosis in HER2-negative breast tumours

    DEFF Research Database (Denmark)

    Paiva, C E; Drigo, S A; Rosa, F E;

    2010-01-01

    BACKGROUND: The clinical relevance of transforming growth factor-beta (TGF-beta)-signalling pathway in breast carcinomas (BCs) remained elusive. This study aimed to evaluate the prognostic value of TGF-beta1 and transforming growth factor-beta type II receptor (TGF-betaRII) expression levels in.......489, P = 0.003]. TGF-betaRII positivity was an independent prognostic factor for DFS (HR = 0.439, P = 0.001) and overall survival (OS) (HR = 0.409, P = 0.003) in human epidermal growth factor receptor-2 (HER2)-negative patients. Absence of TGF-beta1 and TGF-betaRII proteins in breast tumour cells was...

  10. 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.)

  11. Persistence of disseminated tumor cells after neoadjuvant treatment for locally advanced breast cancer predicts poor survival

    OpenAIRE

    Mathiesen, Randi R.; Borgen, Elin; Renolen, Anne; Løkkevik, Erik; Nesland, Jahn M; Anker, Gun; Østenstad, Bjørn; Lundgren, Steinar; Risberg, Terje; Mjaaland, Ingvil; Kvalheim, Gunnar; Lønning, Per E.; Naume, Bjørn

    2012-01-01

    Introduction Presence of disseminated tumor cells (DTCs) in bone marrow (BM) and circulating tumor cells (CTC) in peripheral blood (PB) predicts reduced survival in early breast cancer. The aim of this study was to determine the presence of and alterations in DTC- and CTC-status in locally advanced breast cancer patients undergoing neoadjuvant chemotherapy (NACT) and to evaluate their prognostic impact. Methods ...

  12. Trastuzumab beyond progression in human epidermal growth factor receptor 2-positive advanced breast cancer: a german breast group 26/breast international group 03-05 study

    DEFF Research Database (Denmark)

    von Minckwitz, Gunter; du Bois, Andreas; Schmidt, Marcus;

    2009-01-01

    : Patients with HER-2-positive breast cancer that progresses during treatment with trastuzumab were randomly assigned to receive capecitabine (2,500 mg/m(2) body-surface area on days 1 through 14 [1,250 mg/m(2) semi-daily]) alone or with continuation of trastuzumab (6 mg/kg body weight) in 3-week cycles. The...... not associated with increased toxicity. CONCLUSION: Continuation of trastuzumab plus capecitabine showed a significant improvement in overall response and time to progression compared with capecitabine alone in women with HER-2-positive breast cancer who experienced progression during trastuzumab......PURPOSE: Trastuzumab shows clinical activity in human epidermal growth factor receptor 2 (HER-2)-positive early and advanced breast cancer. In the German Breast Group 26/Breast International Group 03-05 trial, we investigated if trastuzumab treatment should be continued beyond progression. METHODS...

  13. Advances in the surgical treatment of breast cancer.

    Science.gov (United States)

    Xing, Lei; He, Qiang; Wang, Yuan-Yuan; Li, Hong-Yuan; Ren, Guo-Sheng

    2016-06-01

    Breast cancer has become the top malignant neoplasm in Chinese women with an increasing risk of morbidity and mortality. As a crucial part of comprehensive treatment of breast cancer, breast surgical technique is ceaselessly ameliorating and enriching its features. With the purpose of achieving minimal surgical intervention and satisfactory cosmetic results, the trend of mammary surgery is focusing on minimally invasive treatment and aesthetics in the 21st century. This article gives an overview of the most representative surgical procedures, such as breast conservative surgery, sentinel lymph node dissection, oncoplastic technique and breast reconstructive surgery. PMID:27265302

  14. 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.

  15. Bones, breasts, and bisphosphonates: rationale for the use of zoledronic acid in advanced and early breast cancer

    Directory of Open Access Journals (Sweden)

    Allan Lipton

    2011-03-01

    Full Text Available Allan LiptonMilton S. Hershey Medical Center, Pennsylvania State University, Hershey, PA, USAAbstract: Bisphosphonates inhibit osteoclast-mediated bone resorption, thereby inhibiting the release of growth factors necessary to promote cancer cell growth, differentiation, and tumor formation in bone. These agents have demonstrated efficacy for delaying the onset and reducing the incidence of skeletal-related events in the advanced breast cancer setting, and have been shown to prevent cancer therapy-induced bone loss in the early breast cancer setting. Emerging clinical data indicate that the role of bisphosphonates in advanced and early breast cancer is evolving. Retrospective analyses and recent clinical trial data show that zoledronic acid may improve outcomes in some patients with breast cancer. Data from ABCSG-12 and ZO-FAST suggest that zoledronic acid may improve disease-free survival in the adjuvant breast cancer setting in postmenopausal women or women with endocrine therapy-induced menopause, and recent data from a predefined subset of the AZURE trial added to the anticancer story. However, the overall negative AZURE trial also raises questions about the role of bisphosphonates as an anticancer agent in patients with breast cancer. Overall, these data suggest that the addition of zoledronic acid to established anticancer regimens may have potential anticancer benefits in specific patient populations, although more studies are required to define its role.Keywords: anticancer, adjuvant therapy, bone metastasis, skeletal, zoledronic acid

  16. Transferrin-bound proteins as potential biomarkers for advanced breast cancer patients

    Directory of Open Access Journals (Sweden)

    Paul Dowling

    2014-12-01

    General significance: Mass spectrometry profiling of Transferrin-bound proteins has revealed serum proteins that can distinguish between serum from advanced breast cancer patients and healthy control subjects with high confidence.

  17. 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.)

  18. 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)

    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.)

  19. Postmastectomy radiotherapy for locally advanced breast cancer receiving neoadjuvant chemotherapy.

    Science.gov (United States)

    Meattini, Icro; Cecchini, Sara; Di Cataldo, Vanessa; Saieva, Calogero; Francolini, Giulio; Scotti, Vieri; Bonomo, Pierluigi; Mangoni, Monica; Greto, Daniela; Nori, Jacopo; Orzalesi, Lorenzo; Casella, Donato; Simoncini, Roberta; Fambrini, Massimiliano; Bianchi, Simonetta; Livi, Lorenzo

    2014-01-01

    Neoadjuvant chemotherapy (NAC) is widely used in locally advanced breast cancer (BC) treatment. The role of postmastectomy radiotherapy (PMRT) after NAC is strongly debated. The aim of our analysis was to identify major prognostic factors in a single-center series, with emphasis on PMRT. From 1997 to 2011, 170 patients were treated with NAC and mastectomy at our center; 98 cases (57.6%) underwent PMRT and 72 cases (42.4%) did not receive radiation. At a median follow-up period of 7.7 years (range 2-16) for the whole cohort, median time to locoregional recurrence (LRR) was 3.3 years (range 0.7-12.4). The 5-year and 10-year actuarial LRR rate were 14.5% and 15.9%, respectively. At the multivariate analysis the factors that significantly correlated with survival outcome were ≥ 4 positive nodes (HR 5.0, 1.51-16.52; P = 0.035), extracapsular extension (HR 2.18, 1.37-3.46; P = 0.009), and estrogen receptor positive disease (HR 0.57, 0.36-0.90; P = 0.003). Concerning LRR according to use of radiation, PMRT reduced LRR for patient with clinical T3 staged disease (P = 0.015). Our experience confirmed the impact of pathological nodal involvement on survival outcome. PMRT was found to improve local control in patients presenting with clinical T3 tumors, regardless of the response to chemotherapy. PMID:25045694

  20. PACLITAXEL PLUS CARBOPLATIN FOR WOMEN WITH ADVANCED BREAST CANCER

    Institute of Scientific and Technical Information of China (English)

    Ju Li; Qing Li; Pin Zhang; Jia-yu Wang; Long-mei Zhao; Bing-he Xu

    2007-01-01

    Objective To evaluate the efficacy and safety of combination chemotherapy with paclitaxel and carboplatin for advanced breast cancer (ABC).Methods From January 2001 to March 2006, 45 patients with ABC were treated with combination chemotherapy of paclitaxel and carboplatin. Patients received infusion of paclitaxel 175 mg/m2 on day 1 every 3 weeks or 75 mg/m2 on day 1,8, 15 every 4 weeks. Carboplatin was administrated on day 2 with a dose of area under the time-concentration curve (AUC) being 5.Results The median number of cycles was 3 (range, 2-6). The overall response rate was 62. 2%. Median time to progression was 7. 0 months (95%CI: 5. 1-8.9). Median overall survival was 29.0 months (95%CI: 20. 1-37.9). One year survival rate was 73. 3%. Response rate for first line and second line treatment were 62. 1 % and 62. 5% , respectively. No significant difference in response existed between visceral metastasis and soft tissue metastasis. The main side effects included nausea/vomiting, neurotoxicity, and hematologic toxicities. Grade HI to IV adverse events included nausea/vomiting in 2 cases (4. 4% ), leukopenia in 17 cases (37. 8% ), and alopecia in 6 cases (13. 3% ).Conclusion Combination of paclitaxel and carboplatin is active in treatment of ABC with an acceptable toxicity profile.

  1. Occult leydig cell tumour and androgen-receptor positive breast cancer in a woman with severe hyperandrogenism

    OpenAIRE

    Saraceno, Giovanna; Barresi, Valeria; Trimarchi, Francesco; Cannavo, Salvatore

    2013-01-01

    Leydig cell tumours represent more than 75% of all testosterone-secreting ovarian masses. These benign tumours are frequently occult or very small, but cause dramatic virilization. Chronic hyperandrogenism can also induce systemic complications, which increase morbidity and mortality risk. One of the most obvious effects of increased testosterone levels is polycythemia, a complication which induces dermatologic, osteoarticular and gastrointestinal manifestations and is associated with increas...

  2. O 6-(4-bromothenyl)guanine reverses temozolomide resistance in human breast tumour MCF-7 cells and xenografts

    OpenAIRE

    Clemons, M.; Kelly, J.; Watson, A.J.; Howell, A.; McElhinney, R S; McMurry, T B H; Margison, G P

    2005-01-01

    Tumour resistance to chemotherapy involving methylating agents such as DTIC (dacarbazine) and temozolomide is linked to expression of the DNA repair protein O 6-alkylguanine-DNA alkyltransferase (MGMT). There is considerable interest in improving the efficacy of such O 6-alkylating chemotherapy by the prior inactivation of MGMT. We have examined the effect of the modified guanine base, O 6-(4-bromothenyl)guanine (PaTrin-2, Patrin™, Lomeguatrib) on MGMT activity and cell or xenograft tumour gr...

  3. Improving the yield of circulating tumour cells facilitates molecular characterisation and recognition of discordant HER2 amplification in breast cancer

    OpenAIRE

    Flores, L M; Kindelberger, D W; Ligon, A H; Capelletti, M.; Fiorentino, M.; Loda, M; Cibas, E S; Jänne, P.A.; Krop, I. E.

    2010-01-01

    Background: Circulating tumour cells (CTCs) offer a non-invasive approach to obtain and characterise metastatic tumour cells, but their usefulness has been limited by low CTC yields from conventional isolation methods. Methods: To improve CTC yields and facilitate their molecular characterisation we compared the Food and Drug Administration-approved CellSearch Epithelial Kit (CEK) to a simplified CTC capture method, CellSearch Profile Kit (CPK), on paired blood samples from patients with meta...

  4. HER2 status and breast cancer therapy: recent advances

    OpenAIRE

    Tripathy, Debu

    2009-01-01

    The phenotype imparted by expression of the HER2 gene in breast cancer and progress made in modifying the disease's natural history through pharmacologically modulating its function has served as a paradigm for rationally targeted therapy and personalized medicine. About 20-25% of breast cancer cases are associated with HER2 gene amplification and overexpression, creating a distinct subtype of breast cancer that is associated with more aggressive behaviour, higher likelihood of overall and br...

  5. Thermoradiotherapy in locally advanced deep seated tumours - thermal parameters and treatment results

    International Nuclear Information System (INIS)

    From October 1987 to December 1990 a total of 37 patients with deep seated tumours of the pelvis (n=34), the abdomen (n=2), or lower leg (n=1) were treated with radiotherapy and regional hyperthermia. Hyperthermia was produced by the BSD-1000 system and the annular phased array (AA) applicator usually driven at 60-80 MHz, or the BSD-2000 system and the Sigma-60 (S 60) applicator usually driven at 70-90 MHz. Detailed thermal mapping and temperature analysis was performed on 29 patients. The overall mean maximum, average and minimum temperature observed was 42.9 ± 2.4 degrees Celsius, 40.9 ± 1.5 degrees Celsius, and 39.3 ± 0.9 degrees Celsius for all treatments. The time-averaged tumour temperatures achieved in 20%, 50% and 90% of all measured temperature sites were 41.8 ± 2.1 degrees Celsius (T20), 40.9 ±1.6 degrees Celsius (T50) and 39.9 ± 1.2 degrees Celsius (T90). In addition, the overall mean maximum, average and minimum temperature measured in normal tissue was 42.4 ±1.4 degrees Celsius, 40.6 ±1.0 degrees Celsius, and 39.2 ±0.9 degrees Celsius. The time averaged normal tissue temperatures achieved in 20%, 50% and 90% of all measured temperature sites were 41.3 ±1.1 degrees Celsius, 40.6 ± 1.1 degrees Celsius, and 39.6 ±1.0 degrees Celsius. In 36 assessable patients, the overall objective response rate was 31%: 2 complete responses (CR) and 9 partial responses (PR). (author). tabs

  6. Comparison of advanced irradiation techniques with photons for benign intracranial tumours

    International Nuclear Information System (INIS)

    Background and purpose: The potential benefits and limitations of different radiation techniques (stereotactic arc therapy (SRS/T), intensity modulated radiotherapy (IMRT), helical tomotherapy (HT), Cyberknife and intensity-modulated multiple arc therapy (AMOA)) have been assessed using comparative treatment planning methods on twelve patients presenting with 'benign' brain tumours. Materials and methods: Plans for five acoustic neurinomas, five meningiomas and two pituitary adenomas were computed to generate dose distributions for all modalities using a common CT dataset to delineate planning target volume and organs at risk. Results: HT, AMOA and IMRT resulted superior to SRS/T and Cyberknife for target coverage. For the first group V 95% ranged from 98% to 100%, minimum dose ranged from 91% to 96% and standard deviation from 0.84% to 1.67%. For organs at risk all techniques respected planning objectives with a tendency of Cyberknife and SRS/T to better spare the brain stem and the healthy brain tissue (e.g., V 20Gy of 2.0% and 2.3%, respectively, compared to 3.1-5.0% for the other techniques). AMOA is in general preferable to IMRT for all OARs. Conformity index (CI95) was better for HT and Cyberknife (both 1.8) and less for AMOA and IMRT (3.9 and 3.0, respectively). Conclusion: All techniques provided good OAR sparing and primarily differed in target coverage indices. For the class of tumours investigated in this report, HT, AMOA and IMRT had better target coverage with HT providing the best combination of indeces. Between AMOA and IMRT, target coverage was comparable and, considering organs at risk, AMOA was slightly preferable

  7. Effects of low-fat and high-fat meals on steady-state pharmacokinetics of lapatinib in patients with advanced solid tumours

    NARCIS (Netherlands)

    Devriese, Lot A; Koch, Kevin M; Mergui-Roelvink, Marja; Matthys, Gemma M; Ma, Wen Wee; Robidoux, Andre; Stephenson, Joe J; Chu, Quincy S C; Orford, Keith W; Cartee, Leanne; Botbyl, Jeff; Arya, Nikita; Schellens, Jan H M

    2014-01-01

    AIM: To quantify the effect of food on the systemic exposure of lapatinib at steady state when administered 1 h before and after meals, and to observe the safety and tolerability of lapatinib under these conditions in patients with advanced solid tumours. METHODS: This was a three-treatment, randomi

  8. Attitudes and treatment outcome of breast conservation therapy for stage I and II breast cancer using peroperative iridium-192 implant boost to the tumour bed

    International Nuclear Information System (INIS)

    Breast conservation therapy for early breast cancer is an established but grossly under-utilized treatment option in India for various reasons. Breast conservation therapy was offered to 200 suitable breast cancer patients between June 1993 and June 1998. Fifty-one patients (25%) opted for breast conservation and the remaining preferred mastectomy. In patients agreeing to conservation therapy, surgery was performed first along with peroperative implantation of iridium-192 to deliver a boost. Whole breast irradiation of 45 Gy was delivered 3-4 weeks after the boost. Cosmesis was assessed at the end of 6 months from completion of therapy. The main reason for refusal of breast conservation therapy was fear of recurrence in the remaining breast (60%). There were no loco-regional failures in our study at a median follow up of 42 months; one patient experienced a systemic relapse. Cosmesis was good to excellent in 80% of patients. Breast conservation therapy using peroperative iridium-192 implant provides excellent loco-regional disease control and cosmesis. The results of our study indicate that patient preference for mastectomy is an important reason for the under-utilization of breast conservation therapy in India. Copyright (2001) Blackwell Science Pty Ltd

  9. Basal 18F-fluoro-2-deoxy-d-glucose positron emission tomography/computed tomography as a prognostic biomarker in patients with locally advanced breast cancer

    International Nuclear Information System (INIS)

    To explore the relationship between basal 18F-FDG PET/CT information in breast tumours and survival in locally advanced breast cancer (LABC). This prospective, multicentre study included 198 women diagnosed with LABC. All patients underwent 18F-FDG PET/CT prior to treatment. The maximum standardized uptake value (SUVmax) in tumor (T), lymph nodes (N) and the N/T ratio was obtained in all cases. Stage according to PET/CT imaging (metabolic stage) and conventional imaging techniques (clinical stage) was established. During follow-up, patient status was established (disease free status or not). The relationship between all the variables and overall survival (OS) and disease-free survival (DFS) was analysed using the Kaplan-Meier and Cox regression methods. A ROC analysis was performed to obtain a cut-off value of SUVmax that was useful in the prediction of outcome. The mean SUVmax ± SD values in the primary tumour, lymph nodes and the SUVmax N/T index were 7.40 ± 5.57, 4.17 ± 4.74 and 0.73 ± 1.20, respectively. Higher semiquantitative metabolic values were found in more advanced metabolic and clinical stages. During follow-up, 78.4 % of patients were free of disease. Significant relationships were observed between SUVT and SUVN and patient status. With respect to OS and DFS, significant differences were detected for the metabolic stage. Kaplan-Meier analysis revealed that using the cut-off values, a primary-tumour SUVmax ≥ 6.05 or a nodal SUVmax ≥2.25 were significantly correlated with DFS and OS. PET imaging with 18F-FDG offers prognostic information for LABC that can be obtained preoperatively and noninvasively. (orig.)

  10. Basal {sup 18}F-fluoro-2-deoxy-d-glucose positron emission tomography/computed tomography as a prognostic biomarker in patients with locally advanced breast cancer

    Energy Technology Data Exchange (ETDEWEB)

    Garcia Vicente, Ana Maria; Soriano Castrejon, Angel [University General Hospital, Nuclear Medicine Department, Ciudad Real (Spain); Lopez-Fidalgo, Jesus Fernando; Amo-Salas, Mariano [University of Castilla-La Mancha, Department of Mathematics, Ciudad Real (Spain); Mar Munoz Sanchez, Maria del [Virgen de la Luz Hospital, Oncology Department, Cuenca (Spain); Alvarez Cabellos, Ruth [Virgen de la Salud Hospital, Oncology Department, Toledo (Spain); Espinosa Aunion, Ruth [La Mancha Centro Hospital, Oncology Department, Ciudad Real (Spain)

    2015-11-15

    To explore the relationship between basal {sup 18}F-FDG PET/CT information in breast tumours and survival in locally advanced breast cancer (LABC). This prospective, multicentre study included 198 women diagnosed with LABC. All patients underwent {sup 18}F-FDG PET/CT prior to treatment. The maximum standardized uptake value (SUVmax) in tumor (T), lymph nodes (N) and the N/T ratio was obtained in all cases. Stage according to PET/CT imaging (metabolic stage) and conventional imaging techniques (clinical stage) was established. During follow-up, patient status was established (disease free status or not). The relationship between all the variables and overall survival (OS) and disease-free survival (DFS) was analysed using the Kaplan-Meier and Cox regression methods. A ROC analysis was performed to obtain a cut-off value of SUVmax that was useful in the prediction of outcome. The mean SUVmax ± SD values in the primary tumour, lymph nodes and the SUVmax N/T index were 7.40 ± 5.57, 4.17 ± 4.74 and 0.73 ± 1.20, respectively. Higher semiquantitative metabolic values were found in more advanced metabolic and clinical stages. During follow-up, 78.4 % of patients were free of disease. Significant relationships were observed between SUVT and SUVN and patient status. With respect to OS and DFS, significant differences were detected for the metabolic stage. Kaplan-Meier analysis revealed that using the cut-off values, a primary-tumour SUVmax ≥ 6.05 or a nodal SUVmax ≥2.25 were significantly correlated with DFS and OS. PET imaging with {sup 18}F-FDG offers prognostic information for LABC that can be obtained preoperatively and noninvasively. (orig.)

  11. Pathophysiology of tumour-induced microangiopathic haemolytic anaemia.

    Science.gov (United States)

    Chalasani, Pavani; Segar, Jennifer M; Marron, Marilyn; Stopeck, Alison

    2016-01-01

    Cancer-associated microangiopathic haemolytic anaemia (CA-MAHA) is a syndrome characterised by Coombs-negative haemolytic anaemia and thrombocytopenia. It is primarily seen in advanced solid tumours and is distinct from thrombotic thrombocytopenic purpura/haemolytic uraemic syndrome. Diagnosis is often delayed and patients have a high mortality. We present the case of CA-MAHA in a patient with metastatic breast cancer treated successfully with early initiation of chemotherapy. In addition, we report longitudinal laboratory evaluation of circulating tumour cells and microparticles and suggest a hypothesis for the mechanism behind CA-MAHA. PMID:26744538

  12. Postmastectomy Radiotherapy for Locally Advanced Breast Cancer Receiving Neoadjuvant Chemotherapy

    Directory of Open Access Journals (Sweden)

    Icro Meattini

    2014-01-01

    Full Text Available Neoadjuvant chemotherapy (NAC is widely used in locally advanced breast cancer (BC treatment. The role of postmastectomy radiotherapy (PMRT after NAC is strongly debated. The aim of our analysis was to identify major prognostic factors in a single-center series, with emphasis on PMRT. From 1997 to 2011, 170 patients were treated with NAC and mastectomy at our center; 98 cases (57.6% underwent PMRT and 72 cases (42.4% did not receive radiation. At a median follow-up period of 7.7 years (range 2–16 for the whole cohort, median time to locoregional recurrence (LRR was 3.3 years (range 0.7–12.4. The 5-year and 10-year actuarial LRR rate were 14.5% and 15.9%, respectively. At the multivariate analysis the factors that significantly correlated with survival outcome were ≥4 positive nodes (HR 5.0, 1.51–16.52; P=0.035, extracapsular extension (HR 2.18, 1.37–3.46; P=0.009, and estrogen receptor positive disease (HR 0.57, 0.36–0.90; P=0.003. Concerning LRR according to use of radiation, PMRT reduced LRR for patient with clinical T3 staged disease (P=0.015. Our experience confirmed the impact of pathological nodal involvement on survival outcome. PMRT was found to improve local control in patients presenting with clinical T3 tumors, regardless of the response to chemotherapy.

  13. Accelerated partial breast irradiation:advances and controversies

    Institute of Scientific and Technical Information of China (English)

    Mani Akhtari; Bin S Teh

    2016-01-01

    The management of localized breast cancer has changed dramatically over the past three to four decades. Breast-conserving therapy, which involved lumpectomy followed by adjuvant irradiation, is now widely considered the standard of care in women with early-stage breast cancer. Accelerated partial breast irradiation (APBI), which involves focal irradiation of the lumpectomy cavity over a short period of time, has developed over the past two decades as an alternative to whole breast irradiation (WBI). Multiple APBI modalities have been developed including brachytherapy, external beam irradiation, and intraoperative irradiation. These new techniques have provided early-stage breast can-cer patients with shorter treatment duration and more focused irradiation, delivering very high biological doses to the region at a high risk of failures over a much shorter treatment course as compared with conventional radiotherapy. However, the advantages of APBI over conventional radiotherapy are controversial, including a higher risk of compli-cations reported in retrospective literature and shorter follow-up duration in the intraoperative APBI trials. Neverthe-less, APBI presents a valuable alternative to WBI for a selected population of women with early-stage breast cancer.

  14. Recent advances in the surgical care of breast cancer patients

    Directory of Open Access Journals (Sweden)

    Vitelli Carlo E

    2010-01-01

    Full Text Available Abstract A tremendous improvement in every aspect of breast cancer management has occurred in the last two decades. Surgeons, once solely interested in the extipartion of the primary tumor, are now faced with the need to incorporate a great deal of information, and to manage increasingly complex tasks. As a comprehensive assessment of all aspects of breast cancer care is beyond the scope of the present paper, the current review will point out some of these innovations, evidence some controversies, and stress the need for the surgeon to specialize in the various aspects of treatment and to be integrated into the multisciplinary breast unit team.

  15. A review of breast tomosynthesis. Part II. Image reconstruction, processing and analysis, and advanced applications.

    Science.gov (United States)

    Sechopoulos, Ioannis

    2013-01-01

    Many important post-acquisition aspects of breast tomosynthesis imaging can impact its clinical performance. Chief among them is the reconstruction algorithm that generates the representation of the three-dimensional breast volume from the acquired projections. But even after reconstruction, additional processes, such as artifact reduction algorithms, computer aided detection and diagnosis, among others, can also impact the performance of breast tomosynthesis in the clinical realm. In this two part paper, a review of breast tomosynthesis research is performed, with an emphasis on its medical physics aspects. In the companion paper, the first part of this review, the research performed relevant to the image acquisition process is examined. This second part will review the research on the post-acquisition aspects, including reconstruction, image processing, and analysis, as well as the advanced applications being investigated for breast tomosynthesis. PMID:23298127

  16. Down-Regulation of miR-92 in Breast Epithelial Cells and in Normal but Not Tumour Fibroblasts Contributes to Breast Carcinogenesis.

    Directory of Open Access Journals (Sweden)

    Laura Smith

    Full Text Available MicroRNA (miR expression is commonly dysregulated in many cancers, including breast. MiR-92 is one of six miRs encoded by the miR-17-92 cluster, one of the best-characterised oncogenic miR clusters. We examined expression of miR-92 in the breast epithelium and stroma during breast cancer progression. We also investigated the role of miR-92 in fibroblasts in vitro and showed that down-regulation in normal fibroblasts enhances the invasion of breast cancer epithelial cells.We used laser microdissection (LMD to isolate epithelial cells from matched normal, DCIS and invasive tissue from 9 breast cancer patients and analysed miR-92 expression by qRT-PCR. Expression of ERβ1, a direct miR-92 target, was concurrently analysed for each case by immunohistochemistry. LMD was also used to isolate matched normal (NFs and cancer-associated fibroblasts (CAFs from 14 further cases. Effects of miR-92 inhibition in fibroblasts on epithelial cell invasion in vitro was examined using a Matrigel™ assay. miR-92 levels decreased in microdissected epithelial cells during breast cancer progression with highest levels in normal breast epithelium, decreasing in DCIS (p<0.01 and being lowest in invasive breast tissue (p<0.01. This was accompanied by a shift in cell localisation of ERβ1 from nuclear expression in normal breast epithelium to increased cytoplasmic expression during progression to DCIS (p = 0.0078 and invasive breast cancer (p = 0.031. ERβ1 immunoreactivity was also seen in stromal fibroblasts in tissues. Where miR-92 expression was low in microdissected NFs this increased in matched CAFs; a trend also seen in cultured primary fibroblasts. Down-regulation of miR-92 levels in NFs but not CAFs enhanced invasion of both MCF-7 and MDA-MB-231 breast cancer epithelial cells.miR-92 is gradually lost in breast epithelial cells during cancer progression correlating with a shift in ERβ1 immunoreactivity from nuclei to the cytoplasm. Our data support a functional

  17. Advancements of antisense oligonucleotides in treatment of breast cancer

    Institute of Scientific and Technical Information of China (English)

    YANGShuan-Ping; SONGSan-Tai; 等

    2003-01-01

    Breast cancer is one kind of multi-gene related malignancy.Overexpression of some oncogenes such as HER-2(c-erbB-2,Neu),bcl-2/bcl-xL,protein kinase A(PKA),and transferrin receptor gene(TfR gene),etc significantly affect the prognosis of breast cancer.It was shown that specific suppression of the overexpressed genes above resulted in the improvement of the therapy of breast cancer.Antisense interference.one of useful tools for inhibiting the overexpression of specific oncogenes,was involved in the therapy of breast cancer in recent years. Data indicated that antisense oligonucleotides(ON)could inhibit specially the expression of the target genes on mRNA or protein levels in most of cases;some ON candidates showed encouraging therapeutic effects in vitro and in vivo on breast cancer cell lines or xenografts.Furthermore,the combination use of the antisense ON and normal chemotherapeutic agents indicated synergistic antitumor effects,which was probably the best utilization of antisense ON in the treatment of breast cancer.

  18. 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)

    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

  19. Reactivation of the tumour suppressor RASSF1A in breast cancer by simultaneous targeting of DNA and E2F1 methylation.

    Directory of Open Access Journals (Sweden)

    María F Montenegro

    Full Text Available BACKGROUND: Tumour suppressor genes are often transcriptionally silenced by promoter hypermethylation, and recent research has implicated alterations in chromatin structure as the mechanistic basis for this repression. In addition to DNA methylation, other epigenetic post-translational modifications that modulate the stability and binding of specific transcription factors to gene promoters have emerged as important mechanisms for controlling gene expression. The aim of this study was to analyse the implications of these mechanisms and their molecular connections in the reactivation of RASSF1A in breast cancer. METHODS: Compounds that modulate the intracellular concentration of adenosine, such as dipyridamole (DIPY, greatly increase the antiproliferative effects of 3-O-(3,4,5-trimethoxybenzoyl-(--catechin (TMCG, a synthetic antifolate derived from the structure of tea catechins. Quantitative real-time PCR arrays and MALDI-TOF mass spectrometry indicated that this combination (TMCG/DIPY induced apoptosis in breast cancer cells by modulating the methylation levels of DNA and proteins (such as E2F1, respectively. Chromatin immunoprecipitation (ChIP assays were employed to confirm that this combination induced chromatin remodelling of the RASSF1A promoter and increased the occupancy of E2F1 at the promoter of this tumour suppressor gene. RESULTS: The TMCG/DIPY combination acted as an epigenetic treatment that reactivated RASSF1A expression and induced apoptosis in breast cancer cells. In addition to modulating DNA methylation and chromatin remodelling, this combination also induced demethylation of the E2F1 transcription factor. The ChIP assay showed enhancement of E2F1 occupancy at the unmethylated RASSF1A promoter after TMCG/DIPY treatment. Interestingly, inhibition of E2F1 demethylation using an irreversible inhibitor of lysine-specific demethylase 1 reduced both TMCG/DIPY-mediated RASSF1A expression and apoptosis in MDA-MB-231 cells, suggesting

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

    Czech Academy of Sciences Publication Activity Database

    Yan, B.; Stantic, M.; Zobalová, Renata; Bezawork-Geleta, A.; Stapelberg, M.; Stursa, J.; Prokopová, Kateřina; Dong, L.; Neužil, Jiří

    2015-01-01

    Roč. 15, č. 401 (2015). ISSN 1471-2407 R&D Projects: GA MZd NT14078; GA MŠk(CZ) ED1.1.00/02.0109 Institutional support: RVO:86652036 Keywords : Tumour-initiating cells * Mitochondrially targeted vitamin E succinate * Complex II Subject RIV: FD - Oncology ; Hematology Impact factor: 3.362, year: 2014

  1. Complete regression of breast tumour with a single dose of docetaxel-entrapped core-cross-linked polymeric micelles

    NARCIS (Netherlands)

    Hu, Qizhi; Rijcken, Cristianne J.; Bansal, Ruchi; Hennink, Wim E.; Storm, Gert; Prakash, Jai

    2015-01-01

    Treatment with chemotherapy such as docetaxel (DTX) is associated with significant toxicity and tumour recurrence. In this study, we developed DTX-entrapped core-cross-linked polymeric micelles (DTX-CCL-PMs, 66 nm size) by covalently conjugating DTX to CCL-PMs via a hydrolysable ester bond. The cova

  2. Bevacizumab for Advanced Breast Cancer: Hope, Hype, and Hundreds of Headlines

    OpenAIRE

    Fralick, Michael; Ray, Monali; Fung, Christina; Booth, Christopher M.; Mallick, Ranjeeta; Clemons, Mark J

    2013-01-01

    In February 2008, the U.S. Food and Drug Administration granted accelerated approval for the use of bevacizumab in metastatic breast cancer; however, approval was revoked in November 2011. We sought to categorize and analyze the newspaper reports related to bevacizumab's use in advanced breast cancer. Media reports are a common source of medical information, and we observed substantial fluidity of media reports over time.

  3. Tumour Fas ligand:Fas ratio greater than 1 is an independent marker of relative resistance to tamoxifen therapy in hormone receptor positive breast cancer

    International Nuclear Information System (INIS)

    The objective of the present study was to examine the prognostic and predictive significance of the apoptosis-related marker Fas ligand (FasL):Fas ratio in breast cancer. Tumour biopsies from 215 primary invasive breast cancer patients were examined for the expression of FasL and Fas mRNA transcripts by quantitative real-time RT-PCR. Their prognostic and predictive impact on patient survival was determined in univariate and multivariate survival analyses. Using a cutoff value of 1, a FasL:Fas ratio greater than 1 was found to have significant prognostic value for disease-free survival among the total population (median follow up 54 months). It was associated with a significantly decreased disease-free survival (P = 0.022) and with a tendency toward increased mortality (P = 0.14) in univariate analysis. Hormone receptor positive women exclusively treated with tamoxifen (n = 86) and with a FasL:Fas ratio greater than 1 had a significantly decreased disease-free survival (P = 0.008) and overall survival (P = 0.03) in univariate Kaplan–Meier analysis. Furthermore, tumour size and FasL:Fas ratio were of independent predictive significance in the multivariate model for disease-free and overall survival in that subgroup. Among postmenopausal patients (n = 148) both of those factors retained independent prognostic significance in the multivariate model for disease-free survival. In contrast, FasL:Fas ratio had no significant predictive value in patients exclusively treated with chemotherapy. The data presented indicate that FasL:Fas ratio may be useful not only as a prognostic factor but also as a predictive factor for projecting response to the antioestrogen tamoxifen. The results strongly support a correlation between FasL:Fas ratio greater than 1 and lack of efficacy of tamoxifen in hormone receptor positive patients

  4. Age at Diagnosis and Breast Cancer Survival in Iran

    Directory of Open Access Journals (Sweden)

    Fatemeh Asadzadeh Vostakolaei

    2012-01-01

    Full Text Available 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 resulting variation in disease management, findings on the association between young age and prognosis of breast cancer are controversial. Methods. This study included 1500 patients with a primary diagnosis of breast cancer in six Iranian hospitals from 5 provinces. We modelled the relative excess risk (RER of breast cancer death to age at diagnosis and tumour characteristics. Results. Excess risks of death were observed for stage IV disease and poorly differentiated tumours: RER of 4.3 (95% CI: 1.05–17.65 and 3.4 (95% CI: 1.17–9.87, respectively. “Older” patients, particularly those aged 50 and over, presented more often with advanced and poorly differentiated tumours (P=0.001. After adjustment for stage, histological grade, Her-2 expression, estrogen and progesterone receptors, and place of residency, breast cancer mortality was not significantly different across age groups. Conclusion. We conclude that there is no prognostic effect of age at diagnosis of breast cancer among breast cancer patients treated at cancer centres in different parts of Iran; young and relatively old women have similar risks of dying from breast cancer.

  5. Higher expression levels of SOCS 1,3,4,7 are associated with earlier tumour stage and better clinical outcome in human breast cancer

    International Nuclear Information System (INIS)

    Suppressors of cytokine signaling (SOCS) are important negative feedback regulators of the JAK/STAT signaling pathway, and have been recently investigated for their role in the development of different cancers. In this study, we examined the expression of SOCS1-7 genes in normal and breast cancer tissue and correlated this with several clinico-pathological and prognostic factors. SOCS1-7 mRNA extraction and reverse transcription were performed on fresh frozen breast cancer tissue samples (n = 127) and normal background breast tissue (n = 31). Transcript levels of expression were determined using real-time PCR and analyzed against TNM stage, tumour grade and clinical outcome over a 10 year follow-up period. SOCS1,4,5,6 and 7 expression decreased with increased TNM stage (TNM1 vs. TNM3 p = 0.039, TNM1 vs. TNM4 p = 0.016, TNM2 vs. TNM4 p = 0.025, TNM1 vs. TNM3 p = 0.012, and TNM1 vs. TNM3 p = 0.044 respectively). SOCS2 and 3 expression decreased with increased Nottingham Prognostic Index (NPI) (NPI1 vs. NPI3 p = 0.033, and NPI2 vs. NPI3 p = 0.041 respectively). SOCS7 expression decreased with higher tumour grade (Grade 3 vs. Grade 2 p = 0.037). After a median follow up period of 10 years, we found higher levels of SOCS1,2 and 7 expression among those patients who remained disease-free compared to those who developed local recurrence (p = 0.0073, p = 0.021, and p = 0.039 respectively). Similarly, we found higher levels of SOCS 2,4, and 7 expression in those who remained disease-free compared to those who developed distant recurrence (p = 0.022, p = 0.024, and p = 0.033 respectively). Patients who remained disease-free had higher levels of SOCS1 and 2 expression compared to those who died from breast cancer (p = 0.02 and p = 0.033 respectively). The disease free survival (DFS) and overall survival (OS) curves showed that higher levels of SOCS1, 3 and 7 were significant predictors of higher DFS (p = 0.015, p = 0.024 and 0.03 respectively) and OS (p = 0.005, p = 0.013 and

  6. Sensitivity and specificity of single and combined tumour markers in the diagnosis of leptomeningeal metastasis from breast cancer.

    OpenAIRE

    Twijnstra, A; van Zanten, A. P.; Nooyen, W J; Ongerboer De Visser, B W

    1986-01-01

    The clinical efficacy of four laboratory tests in detecting leptomeningeal metastases in 57 patients with breast carcinoma was assessed. The sensitivity and specificity of beta-glucuronidase, beta 2-microglobulin, carcinoembryonic antigen and lactate dehydrogenase in cerebrospinal fluid were determined. As a single test beta-glucuronidase was the most sensitive (93%) and specific (93%) for discriminating between leptomeningeal metastases and other CNS metastases from breast cancer. Lactate de...

  7. Lack of relationship between TIMP-1 tumour cell immunoreactivity, treatment efficacy and prognosis in patients with advanced epithelial ovarian cancer

    DEFF Research Database (Denmark)

    Steffensen, Karina Dahl; Waldstrøm, Marianne; Christensen, Rikke Kølby;

    2010-01-01

    BACKGROUND: Tissue inhibitor of metalloproteinase 1 (TIMP-1) is a natural inhibitor of the matrix metalloproteinases (MMPs) which are proteolytic enzymes involved in degradation of extracellular matrix thereby favoring tumour cell invasion and metastasis. TIMP-1 activity in tumour tissue may...

  8. A clinical study of radiotherapy with CHFU for advanced and recurrent breast cancer

    International Nuclear Information System (INIS)

    We have investigated the usefulness of combination therapy with radiation and CHFU for advanced and recurrent breast cancer according to a clinical cotrolled multicenter trial from 1982 to 1984. One hundred cases were registered and 82 of them were availabe. Treatment sites were the lymph nodes, skin, bone and lung, and the overall response rate was 58% in CR and 19% in PR, while the duration of remission was 18 weeks in CR. Side effects were found in 10% of the patients. Combination therapy with radiation and HCFU may be useful in multimodal tretment for advanced recurrent breast cancer. (author)

  9. Primary tumour–vessel tumour–nodal tumour classification for patients with invasive ductal carcinoma of the breast

    OpenAIRE

    Hasebe, T; SASAKI, S.; S. Imoto; Wada, N; Ishii, G; Ochiai, A.

    2005-01-01

    There are many studies that show biological differences between invasive ductal carcinoma (IDC) with and without nodal metastasis, but no prognostic classification taking into consideration any biological differences between them is currently available. We previously investigated the histological characteristics that play an important role in tumour progression of IDCs according to their nodal status, and a new prognostic histological classification, the primary tumour–vessel tumour–nodal tum...

  10. Which techniques for an additional irradiation of the tumour bed in a breast cancer?; Quelles techniques de complement d'irradiation du lit tumoral dans le cancer du sein?

    Energy Technology Data Exchange (ETDEWEB)

    Chenna, H.; Iraqi, M.; Ahmedou, M.M.; Berhil, H.; El Kacemi, H.; Hassouni, K.; Kebdani, T.; Benjaafar, N.; El Gueddari, B.K. [Service de radiotherapie, Institut national d' oncologie, Rabat (Morocco)

    2010-10-15

    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

  11. 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)

    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

  12. Contribution of 18-FDG-PET/TC in the handling of the locally advanced stadiums of breast cancer

    International Nuclear Information System (INIS)

    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)

  13. Dissecting the Role of Curcumin in Tumour Growth and Angiogenesis in Mouse Model of Human Breast Cancer

    Directory of Open Access Journals (Sweden)

    Sabrina Bimonte

    2015-01-01

    Full Text Available Breast cancer is considered the most common cancer for women worldwide and it is now the second leading cause of cancer-related deaths among females in the world. Since breast cancer is highly resistant to chemotherapy, alternative anticancer strategies have been developed. In particular, many studies have demonstrated that curcumin, a derivative of turmeric, can be used as natural agent in treatment of some types of cancer by playing antiproliferative and antioxidant effects. In our study, we assessed the antitumor activities of curcumin in ER-negative human breast cancer cell line resistant to chemotherapy, MDA.MB231 by in vitro and in vivo experiments. In vitro data allowed us to demonstrate that curcumin played a role in regulation of proliferation and apoptosis in MDA.MB231 cells. In vivo, by generation of mouse model of breast cancer, we showed that treatment of curcumin inhibited tumor growth and angiogenesis. Specifically, we showed that curcumin is able to deregulate the expression of cyclin D1, PECAM-1, and p65, which are regulated by NF-κB. Our data demonstrated that curcumin could be used as an adjuvant agent to chemotherapy in treatment of triple negative breast cancer.

  14. Contrast-enhanced spectral mammography versus MRI: Initial results in the detection of breast cancer and assessment of tumour size

    Energy Technology Data Exchange (ETDEWEB)

    Fallenberg, E.M.; Renz, D.M. [Charite - Universitaetsmedizin Berlin, Clinic of Radiology, Berlin (Germany); Dromain, C. [Institut Gustave Roussy, Department of Radiology, Villejuif cedex (France); Diekmann, F. [St. Joseph-Stift Bremen, Department of Medical Imaging, Bremen (Germany); Engelken, F.; Krohn, M.; Singh, J.M.; Bick, U. [Charite - Universitaetsmedizin Berlin, Department of Radiology, Berlin (Germany); Ingold-Heppner, B. [Charite - Universitaetsmedizin Berlin, Institute of Pathology, Berlin (Germany); Winzer, K.J. [Charite - Universitaetsmedizin Berlin, Breast Center, Department of Gynecology, Berlin (Germany)

    2014-01-15

    To compare mammography (MG), contrast-enhanced spectral mammography (CESM), and magnetic resonance imaging (MRI) in the detection and size estimation of histologically proven breast cancers using postoperative histology as the gold standard. After ethical approval, 80 women with newly diagnosed breast cancer underwent MG, CESM, and MRI examinations. CESM was reviewed by an independent experienced radiologist, and the maximum dimension of suspicious lesions was measured. For MG and MRI, routine clinical reports of breast specialists, with judgment based on the BI-RADS lexicon, were used. Results of each imaging technique were correlated to define the index cancer. Fifty-nine cases could be compared to postoperative histology for size estimation. Breast cancer was visible in 66/80 MG, 80/80 CESM, and 77/79 MRI examinations. Average lesion largest dimension was 27.31 mm (SD 22.18) in MG, 31.62 mm (SD 24.41) in CESM, and 27.72 mm (SD 21.51) in MRI versus 32.51 mm (SD 29.03) in postoperative histology. No significant difference was found between lesion size measurement on MRI and CESM compared with histopathology. Our initial results show a better sensitivity of CESM and MRI in breast cancer detection than MG and a good correlation with postoperative histology in size assessment. (orig.)

  15. Contrast-enhanced spectral mammography versus MRI: Initial results in the detection of breast cancer and assessment of tumour size

    International Nuclear Information System (INIS)

    To compare mammography (MG), contrast-enhanced spectral mammography (CESM), and magnetic resonance imaging (MRI) in the detection and size estimation of histologically proven breast cancers using postoperative histology as the gold standard. After ethical approval, 80 women with newly diagnosed breast cancer underwent MG, CESM, and MRI examinations. CESM was reviewed by an independent experienced radiologist, and the maximum dimension of suspicious lesions was measured. For MG and MRI, routine clinical reports of breast specialists, with judgment based on the BI-RADS lexicon, were used. Results of each imaging technique were correlated to define the index cancer. Fifty-nine cases could be compared to postoperative histology for size estimation. Breast cancer was visible in 66/80 MG, 80/80 CESM, and 77/79 MRI examinations. Average lesion largest dimension was 27.31 mm (SD 22.18) in MG, 31.62 mm (SD 24.41) in CESM, and 27.72 mm (SD 21.51) in MRI versus 32.51 mm (SD 29.03) in postoperative histology. No significant difference was found between lesion size measurement on MRI and CESM compared with histopathology. Our initial results show a better sensitivity of CESM and MRI in breast cancer detection than MG and a good correlation with postoperative histology in size assessment. (orig.)

  16. The use of tumour markers CEA, CA-195 and CA-242 in evaluating the response to chemotherapy in patients with advanced colorectal cancer.

    OpenAIRE

    Ward, U.; Primrose, J N; Finan, P. J.; Perren, T. J.; Selby, P.; Purves, D. A.; Cooper, E H

    1993-01-01

    Tumour markers CEA, CA-195 and CA-242 were measured in 33 patients undergoing chemotherapy for advanced colorectal cancer. The aim was to determine whether they could be used to accurately monitor the course of the disease, and reduce the need for imaging. Treatment with a 5-fluorouracil based regimen resulted in a partial response in nine patients (27%), whereas the remainder either had disease stabilisation or suffered from progression. Before treatment the CEA was elevated in 85% of patien...

  17. Rasburicase in the prevention of laboratory/clinical tumour lysis syndrome in children with advanced mature B-NHL: A Children’s Oncology Group Report

    OpenAIRE

    Galardy, Paul; Hochberg, Jessica; Perkins, Sherrie L.; Harrison, Lauren; Goldman, Stanton; Cairo, Mitchell S

    2013-01-01

    Laboratory (LTLS) and clinical (CTLS) tumour lysis syndrome (TLS) are frequent complications in newly diagnosed children with advanced mature B cell non-Hodgkin lymphoma (B-NHL). Rasburicase, compared to allopurinol, results in more rapid reduction of uric acid in paediatric patients at risk for TLS. However, the safety and efficacy of rasburicase for the treatment or or prevention of TLS has not been prospectively evaluated. Children with newly diagnosed stage III–IV, bone marrow+ and/or cen...

  18. Nestin expression associates with poor prognosis and triple negative phenotype in locally advanced (T4 breast cancer

    Directory of Open Access Journals (Sweden)

    F. Piras

    2011-11-01

    Full Text Available Nestin, an intermediate filament protein, has traditionally been noted for its importance as a neural stem cell marker. However, in recent years, expression of nestin has shown to be associated with general proliferation of progenitor cell populations within neoplasms. There is no reported study addressing nestin expression in T4 breast cancer patients. Thus, the aim of the present study was to investigate, through immunohistochemistry, the expression and distribution of nestin in T4 breast cancer, in order to determine its association with clinical and pathological parameters as well as with patients’ outcome. Nestin was detectable in tumoral cells and in endothelial cells of blood microvessels, and it is significantly expressed in triple-negative and in inflammatory breast cancer (IBC subgroups of T4 breast tumours. The Kaplan-Meier analysis showed that the presence of nestin in tumoral cells significantly predicted poor prognosis at 5-years survival (P=0.02 and with borderline significance at 10-years of survival (P=0.05 in T4 breast cancer patients. On the basis of these observations, we speculate that nestin expression may characterize tumours with an aggressive clinical behavior, suggesting that the presence of nestin in tumoral cells and vessels may be considered an important factor that leads to a poor prognosis. Further studies are awaited to define the biological role of nestin in the etiology of these subgroups of breast cancers.

  19. Quantitative ultrasound characterization of locally advanced breast cancer by estimation of its scatterer properties

    Energy Technology Data Exchange (ETDEWEB)

    Tadayyon, Hadi [Physical Sciences, Sunnybrook Research Institute, Sunnybrook Health Sciences Centre, Toronto, Ontario M4N 3M5 (Canada); Department of Medical Biophysics, Faculty of Medicine, University of Toronto, Toronto, Ontario M5G 2M9 (Canada); Sadeghi-Naini, Ali; Czarnota, Gregory, E-mail: Gregory.Czarnota@sunnybrook.ca [Physical Sciences, Sunnybrook Research Institute, Sunnybrook Health Sciences Centre, Toronto, Ontario M4N 3M5 (Canada); Department of Medical Biophysics, Faculty of Medicine, University of Toronto, Toronto, Ontario M5G 2M9 (Canada); Department of Radiation Oncology, Odette Cancer Centre, Sunnybrook Health Sciences Centre, Toronto, Ontario M4N 3M5 (Canada); Department of Radiation Oncology, Faculty of Medicine, University of Toronto, Toronto, Ontario M5T 1P5 (Canada); Wirtzfeld, Lauren [Department of Physics, Ryerson University, Toronto, Ontario M5B 2K3 (Canada); Wright, Frances C. [Division of Surgical Oncology, Sunnybrook Health Sciences Centre, Toronto, Ontario M4N 3M5 (Canada)

    2014-01-15

    Purpose: Tumor grading is an important part of breast cancer diagnosis and currently requires biopsy as its standard. Here, the authors investigate quantitative ultrasound parameters in locally advanced breast cancers that can potentially separate tumors from normal breast tissue and differentiate tumor grades. Methods: Ultrasound images and radiofrequency data from 42 locally advanced breast cancer patients were acquired and analyzed. Parameters related to the linear regression of the power spectrum—midband fit, slope, and 0-MHz-intercept—were determined from breast tumors and normal breast tissues. Mean scatterer spacing was estimated from the spectral autocorrelation, and the effective scatterer diameter and effective acoustic concentration were estimated from the Gaussian form factor. Parametric maps of each quantitative ultrasound parameter were constructed from the gated radiofrequency segments in tumor and normal tissue regions of interest. In addition to the mean values of the parametric maps, higher order statistical features, computed from gray-level co-occurrence matrices were also determined and used for characterization. Finally, linear and quadratic discriminant analyses were performed using combinations of quantitative ultrasound parameters to classify breast tissues. Results: Quantitative ultrasound parameters were found to be statistically different between tumor and normal tissue (p < 0.05). The combination of effective acoustic concentration and mean scatterer spacing could separate tumor from normal tissue with 82% accuracy, while the addition of effective scatterer diameter to the combination did not provide significant improvement (83% accuracy). Furthermore, the two advanced parameters, including effective scatterer diameter and mean scatterer spacing, were found to be statistically differentiating among grade I, II, and III tumors (p = 0.014 for scatterer spacing, p = 0.035 for effective scatterer diameter). The separation of the tumor

  20. Quantitative ultrasound characterization of locally advanced breast cancer by estimation of its scatterer properties

    International Nuclear Information System (INIS)

    Purpose: Tumor grading is an important part of breast cancer diagnosis and currently requires biopsy as its standard. Here, the authors investigate quantitative ultrasound parameters in locally advanced breast cancers that can potentially separate tumors from normal breast tissue and differentiate tumor grades. Methods: Ultrasound images and radiofrequency data from 42 locally advanced breast cancer patients were acquired and analyzed. Parameters related to the linear regression of the power spectrum—midband fit, slope, and 0-MHz-intercept—were determined from breast tumors and normal breast tissues. Mean scatterer spacing was estimated from the spectral autocorrelation, and the effective scatterer diameter and effective acoustic concentration were estimated from the Gaussian form factor. Parametric maps of each quantitative ultrasound parameter were constructed from the gated radiofrequency segments in tumor and normal tissue regions of interest. In addition to the mean values of the parametric maps, higher order statistical features, computed from gray-level co-occurrence matrices were also determined and used for characterization. Finally, linear and quadratic discriminant analyses were performed using combinations of quantitative ultrasound parameters to classify breast tissues. Results: Quantitative ultrasound parameters were found to be statistically different between tumor and normal tissue (p < 0.05). The combination of effective acoustic concentration and mean scatterer spacing could separate tumor from normal tissue with 82% accuracy, while the addition of effective scatterer diameter to the combination did not provide significant improvement (83% accuracy). Furthermore, the two advanced parameters, including effective scatterer diameter and mean scatterer spacing, were found to be statistically differentiating among grade I, II, and III tumors (p = 0.014 for scatterer spacing, p = 0.035 for effective scatterer diameter). The separation of the tumor

  1. Accelerated partial breast irradiation trials: Diversity in rationale and design

    International Nuclear Information System (INIS)

    Seven randomised trials are currently testing accelerated partial breast irradiation against whole breast radiotherapy after breast conservation surgery. The trials are varied in the techniques used to deliver partial breast radiotherapy, reflecting the range of opportunities offered by advanced brachytherapy and teletherapy modalities. Dose schedules also vary between trials, but the most important point of difference between them reflects alternative concepts of clinical and planning target volumes. These are based mainly on the spatial pattern of relapse in retrospective and prospective studies, which report the majority of first local relapses close to the primary tumour site, and on the assumption that radiotherapy does not prevent the development of new primary tumours developing elsewhere in the breast. However, the pattern of ipsilateral breast tumour relapse is not accurately defined in the clinical literature and does not correspond closely to pathological findings. In addition, published data are consistent with a significant reduction in the rate of other quadrant relapse after whole breast radiotherapy. Regardless of the biological model of local tumour relapse and responsiveness to radiation, the ongoing trials will generate level I evidence for or against accelerated partial breast irradiation, provided patients are followed up long enough before the first reporting of results.

  2. The usefulness of samarium-135 in advanced breast cancer

    International Nuclear Information System (INIS)

    Full text of publication follows. Introduction: breast cancer is a solid cancer which can often be complicated by metastatic bone pain, reducing performance status and decreasing the quality of life. Quadramet is a radiopharmaceutical consisting of stable complexes of radioactive Samarium (Sm-153) and tetra-phosphonate chelators (EDTMP), having a high affinity to the skeleton more intense in osteoblastic lesions. It is indicated as a palliative measure for the relief of pain from metastatic lesions that enhance on bone scans. Our aim was to assess the effect of Sm-153 in breast cancer. Methods: the study included 10 patients with breast cancer (mean age 43, 5 years) with multiple bone painful metastases detected by scintigraphy. Each patient received 37 MBq/kg of Sm-153. For assessment of therapy effectiveness; pain relief, a reduction in analgesic requirements and motor activity (Karnofsky scale) were evaluated with a receding of 36 months. Results: palliative therapy using Sm-153 is effective (in 2/3 of cases 'good' and 'moderate' response rate) and we have observed that the analgesic requirements decreased to 40% of dose on average. The motor activity of the points evaluated according to Karnofsky scale increased from 50 to 70. Conclusion: in breast cancer, bone metastasis is a major complication which is most often associated with pain. Bone pain palliation therapy with Sm-153 is a cost-effective systemic therapy to relieve pain from skeletal metastases with a consequent decrease in morbidity and an improvement in quality of life

  3. Lapatinib : clinical benefit in patients with HER2-positive advanced breast cancer

    NARCIS (Netherlands)

    Kroep, J. R.; Linn, S. C.; Boven, E.; Bloemendal, H. J.; Baas, J.; Mandjes, I. A. M.; Smit, W. M.; de Graaf, H.; Schroder, C. P.; Vermeulen, G. J.; Hop, W. C. J.; Nortier, J. W. R.

    2010-01-01

    Background: Lapatinib, a tyrosine kinase inhibitor of human epidermal growth factor receptor 2 (HER2), has shown activity in combination with capecitabine in patients with HER2-positive advanced breast cancer progressive on standard treatment regimens. We present results on preapproval drug access f

  4. Management of radiation necrosis and advanced cancer of the chest wall in patients with breast malignancy

    International Nuclear Information System (INIS)

    Aggressive resection, with individualized reconstruction by several methods, is of value in many patients with radiation necrosis and/or advanced breast cancer of the chest wall. Although this does not always significantly lengthen survival, it can improve the quality of life markedly in many instances. Remarkably large defects can be reconstructed with single-stage procedures

  5. A Case of Locally Advanced Breast Cancer Complicated by Pulmonary Tumor Thrombotic Microangiopathy

    OpenAIRE

    Kim, Hak Jin; Kwak, Mi Hyang; Kong, Sun-Young; Seong, Moon-Woo; Kang, Han-Sung; Lee, Keun Seok; Ro, Jungsil

    2012-01-01

    Pulmonary tumor thrombotic microangiopathy (PTTM) is a rare, malignancy-related complication that causes marked pulmonary hypertension, right heart failure, and death. We report on a patient with locally advanced breast cancer whose course was complicated by fatal PTTM based on clinical and laboratory findings.

  6. HSP90 Inhibitor AT13387 and Paclitaxel in Treating Patients With Advanced Triple Negative Breast Cancer

    Science.gov (United States)

    2016-08-08

    Estrogen Receptor Negative; HER2/Neu Negative; Progesterone Receptor Negative; Recurrent Breast Carcinoma; Stage IIIA Breast Cancer; Stage IIIB Breast Cancer; Stage IIIC Breast Cancer; Stage IV Breast Cancer; Triple-Negative Breast Carcinoma

  7. Lack of relationship between TIMP-1 tumour cell immunoreactivity, treatment efficacy and prognosis in patients with advanced epithelial ovarian cancer

    International Nuclear Information System (INIS)

    Tissue inhibitor of metalloproteinase 1 (TIMP-1) is a natural inhibitor of the matrix metalloproteinases (MMPs) which are proteolytic enzymes involved in degradation of extracellular matrix thereby favoring tumour cell invasion and metastasis. TIMP-1 activity in tumour tissue may therefore play an essential role in the progression of a malignant tumour. The primary aim of the present study was to evaluate TIMP-1 protein immunoreactivity in tissue from primary ovarian cancer patients and associate these findings with the course of the disease including response to treatment in the individual patient. TIMP-1 was assessed by immunohistochemistry (in tissue micro arrays) in a total of 163 ovarian cancer specimens obtained from primary debulking surgery during 1991-1994 as part of a randomized clinical protocol. Positive TIMP-1 immunoreactivity was found in 12.3% of the tumours. The median survival time for the 143 patients with TIMP-1 negative tumours was 23.7 months [19.0-29.4] 95% CI, while the median survival time for the 20 patients with TIMP-1 positive tumours was 15.9 months [12.3-27.4] 95% CI. Although a difference of 7.8 months in median overall survival in favor of the TIMP-1 tumour negative patients was found, this difference did not reach statistical significance (p = 0.28, Kaplan-Meier, log-rank test). Moreover, TIMP-1 immunoreactivity was not associated with CA125 response (p = 0.53) or response at second look surgery (p = 0.72). TIMP-1 immunoreactivity in tumour tissue from patients with primary epithelial ovarian cancer did not correlate with patient survival or response to combination platinum/cyclophosphamide therapy

  8. Phase I and pharmacokinetic study of combined treatment with perifosine and radiation in patients with advanced solid tumours

    International Nuclear Information System (INIS)

    Purpose: Perifosine is an orally applicable, membrane-targeted alkylphosphocholine analogue with antitumour activity and radiosensitising properties in preclinical models. The purpose of this phase I study was to determine the feasibility and tolerability of concurrent daily perifosine and radiation in patients with advanced cancer. Patients and methods: Starting dose of perifosine was 50 mg/day; dose escalation was in steps of 50 mg. Daily administration commenced 2 days before radiotherapy and was continued throughout the radiation treatment. At least three patients were entered at each dose level; at the 150 mg/day level 10 patients were included. Pharmacokinetic sampling was performed weekly pre-dosing. Twenty-one patients were entered. Tumour types included NSCLC (n = 17), prostate, oesophageal, colon and bladder cancer. Most patients (16/21) had received prior chemotherapy; none radiotherapy. Median number of daily perifosine administrations was 31 (range 24-53). Mean radiation dose (BED1) was 59.8 Gy (range 50.7-87.5 Gy in 13-28 fractions). Results: Major drug-related toxicities according to CTC criteria were nausea in 57%, fatigue in 48%, vomiting in 38%, diarrhoea in 38% and anorexia in 19%. No bone marrow toxicity was observed. DLT (nausea/vomiting) was encountered in two of five patients at the 200 mg/day dose level. Dose-dependent steady-state plasma levels were reached after 1 week. Major radiotherapy-related acute toxicity consisted of dysphagia in 38% and pneumonitis in 29%. Conclusion: Perifosine can be safely combined with fractionated radiotherapy. A dosage of 150 mg/day, to be started at least 1 week prior to radiotherapy, is recommended for phase II evaluation

  9. Pharmacogenetics-Guided Phase I Study of Capecitabine on an Intermittent Schedule in Patients with Advanced or Metastatic Solid Tumours.

    Science.gov (United States)

    Soo, Ross Andrew; Syn, Nicholas; Lee, Soo-Chin; Wang, Lingzhi; Lim, Xn-Yii; Loh, Marie; Tan, Sing-Huang; Zee, Ying-Kiat; Wong, Andrea Li-Ann; Chuah, Benjamin; Chan, Daniel; Lim, Siew-Eng; Goh, Boon-Cher; Soong, Richie; Yong, Wei-Peng

    2016-01-01

    The FDA-approved starting dosage of capecitabine is 1,250 mg/m(2), and market research indicates that U.S. physicians routinely prescribe 1,000 mg/m(2). Retrospective analyses however report reduced toxicity and efficacy in a subset of patients with the 3R/3R genotype of the thymidylate synthase gene enhancer region (TSER). This study sought to develop TSER genotype-specific guidelines for capecitabine dosing. Capecitabine was dose-escalated in advanced and/or metastatic cancer patients with TSER 3R/3R (Group A; N = 18) or 2R/2R + 2R/3R (Group B; N = 5) from 1,250 to 1,625 mg/m(2) b.i.d., every 2 weeks on/1 week off for up to 8 cycles. Parent and metabolites pharmacokinetics, adverse events, and tumour response were assessed. The maximum tolerated and recommended doses in 3R/3R patients are 1,625 mg/m(2) and 1,500 mg/m(2). At 1,500 mg/m(2), one in nine 3R/3R patients experienced a dose-limiting toxicity. Dosing guidelines for 2R/2R + 2R/3R remain undetermined due to poor accrual. The results indicate that 3R/3R patients may be amenable to 1,500 mg/m(2) b.i.d. on an intermittent schedule, and is the first to prospectively validate the utility of TSER pharmacogenetic-testing before capecitabine treatment. PMID:27296624

  10. Novel polysaccharide anti-tumour drug delivery system for active targeting and controlled release to breast cancer bone metastases

    OpenAIRE

    Bonzi, Gwénaëlle A.M.

    2014-01-01

    ABSTRACT In the late stage of the disease, breast cancer patients often develop bone metastases, a major cause of cancer-related death among women worldwide. The common treatment currently used clinically includes the anti-neoplastic agent paclitaxel combined with the bisphosphonate alendronate. Paclitaxel is an anti-neoplastic drug which cytotoxic effect is mainly attributed to its ability to promote the assembly of microtubules as well as prevent the depolymerisation of these micro...

  11. Recent advances in technologies for the detection of occult metastatic cells in bone marrow of breast cancer patients

    International Nuclear Information System (INIS)

    Approximately half of breast cancer patients with stage I–III disease will suffer metastatic disease despite resection with tumour-free margins. In 30–40% of these patients, individual carcinoma cells can already be detected at the time of primary therapy in cytological bone marrow preparations using immunocytochemistry. Numerous prospective clinical studies have shown that the presence of occult metastatic cells in bone marrow is prognostically relevant to patient survival. Only a few studies failed to do so, thus stimulating a critical discussion on the methodology and clinical value of bone marrow analysis. The potential for obtaining improved prognostic information on patient outcome, for monitoring tumour cell eradication during adjuvant and palliative systemic therapy, and for specifically targeting tumour biological therapies are intriguing clinical opportunities that may be afforded by bone marrow analysis. Standardized and robust methodology is a prerequisite for clinical application of these techniques, however

  12. [Recent advance in adjuvant therapy for breast cancer].

    Science.gov (United States)

    Shimizu, Chikako; Watanabe, Toru

    2002-12-01

    Adjuvant systemic therapy has contributed to a significant improvement of disease-free and overall survival in addition to surgery and irradiation to the local disease. The adjuvant therapy to a patient is determined integrating the information on estimated risk of recurrence, benefit and harm of the therapy and the patient's value. In this review, the state of the art of adjuvant therapy is discussed from several aspects, such as interpretation and evaluation of risk, the best available evidences on adjuvant systemic therapy, the future direction of primary therapy for breast cancer, and patient-oriented decision making. PMID:12506467

  13. Merging transcriptomics and metabolomics - advances in breast cancer profiling

    Directory of Open Access Journals (Sweden)

    Bathen Tone F

    2010-11-01

    Full Text Available Abstract Background Combining gene expression microarrays and high resolution magic angle spinning magnetic resonance spectroscopy (HR MAS MRS of the same tissue samples enables comparison of the transcriptional and metabolic profiles of breast cancer. The aim of this study was to explore the potential of combining these two different types of information. Methods Breast cancer tissue from 46 patients was analyzed by HR MAS MRS followed by gene expression microarrays. Two strategies were used to combine the gene expression and metabolic data; first using multivariate analyses to identify different groups based on gene expression and metabolic data; second correlating levels of specific metabolites to transcripts to suggest new hypotheses of connections between metabolite levels and the underlying biological processes. A parallel study was designed to address experimental issues of combining microarrays and HR MAS MRS. Results In the first strategy, using the microarray data and previously reported molecular classification methods, the majority of samples were classified as luminal A. Three subgroups of luminal A tumors were identified based on hierarchical clustering of the HR MAS MR spectra. The samples in one of the subgroups, designated A2, showed significantly lower glucose and higher alanine levels than the other luminal A samples, suggesting a higher glycolytic activity in these tumors. This group was also enriched for genes annotated with Gene Ontology (GO terms related to cell cycle and DNA repair. In the second strategy, the correlations between concentrations of myo-inositol, glycine, taurine, glycerophosphocholine, phosphocholine, choline and creatine and all transcripts in the filtered microarray data were investigated. GO-terms related to the extracellular matrix were enriched among the genes that correlated the most to myo-inositol and taurine, while cell cycle related GO-terms were enriched for the genes that correlated the most

  14. Merging transcriptomics and metabolomics - advances in breast cancer profiling

    International Nuclear Information System (INIS)

    Combining gene expression microarrays and high resolution magic angle spinning magnetic resonance spectroscopy (HR MAS MRS) of the same tissue samples enables comparison of the transcriptional and metabolic profiles of breast cancer. The aim of this study was to explore the potential of combining these two different types of information. Breast cancer tissue from 46 patients was analyzed by HR MAS MRS followed by gene expression microarrays. Two strategies were used to combine the gene expression and metabolic data; first using multivariate analyses to identify different groups based on gene expression and metabolic data; second correlating levels of specific metabolites to transcripts to suggest new hypotheses of connections between metabolite levels and the underlying biological processes. A parallel study was designed to address experimental issues of combining microarrays and HR MAS MRS. In the first strategy, using the microarray data and previously reported molecular classification methods, the majority of samples were classified as luminal A. Three subgroups of luminal A tumors were identified based on hierarchical clustering of the HR MAS MR spectra. The samples in one of the subgroups, designated A2, showed significantly lower glucose and higher alanine levels than the other luminal A samples, suggesting a higher glycolytic activity in these tumors. This group was also enriched for genes annotated with Gene Ontology (GO) terms related to cell cycle and DNA repair. In the second strategy, the correlations between concentrations of myo-inositol, glycine, taurine, glycerophosphocholine, phosphocholine, choline and creatine and all transcripts in the filtered microarray data were investigated. GO-terms related to the extracellular matrix were enriched among the genes that correlated the most to myo-inositol and taurine, while cell cycle related GO-terms were enriched for the genes that correlated the most to choline. Additionally, a subset of transcripts was

  15. Targeted delivery of albumin bound paclitaxel in the treatment of advanced breast cancer

    Directory of Open Access Journals (Sweden)

    Francesco Di Costanzo

    2009-07-01

    Full Text Available Francesco Di Costanzo,1 Silvia Gasperoni,1 Virginia Rotella,1 Federica Di Costanzo21Struttura Complessa Oncologia Medica, Azienda Ospedaliero Universitaria Careggi, Florence; 2Servizio di Oncologia: Ospedale S: Maria della Stella, Orvieto, ItalyAbstract: Taxanes are chemotherapeutic agents with a large spectrum of antitumor activity when used as monotherapy or in combination regimens. Paclitaxel and docetaxel have poor solubility and require a complex solvent system for their commercial formulation, Cremophor EL® (CrEL and Tween 80® respectively. Both these biological surfactants have recently been implicated as contributing not only to the hypersensitivity reactions, but also to the degree of peripheral neurotoxicity and myelosuppression, and may antagonize the cytotoxicity. Nab-paclitaxel, or nanoparticle albumin-bound paclitaxel (ABI-007; Abraxane®, is a novel formulation of paclitaxel that does not employ the CrEL solvent system. Nab-paclitaxel demonstrates greater efficacy and a favorable safety profile compared with standard paclitaxel in patients with advanced disease (breast cancer, non-small cell lung cancer, melanoma, ovarian cancer. Clinical studies in breast cancer have shown that nab-paclitaxel is significantly more effective than standard paclitaxel in terms of overall objective response rate (ORR and time to progression. Nab-paclitaxel in combination with gemcitabine, capecitabine or bevacizumab has been shown to be very active in patients with advanced breast cancer. An economic analysis showed that nab-paclitaxel would be an economically reasonable alternative to docetaxel or standard paclitaxel in metastatic breast cancer. Favorable tumor ORR and manageable toxicities have been reported for nab-paclitaxel as monotherapy or in combination treatment in advanced breast cancer.Keywords: breast cancer, nab-paclitaxel, chemotherapy

  16. 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.

  17. ENDOCRINE TREATMENT OPTIONS FOR ADVANCED BREAST CANCER — THE ROLE OF FULVESTRANT

    Directory of Open Access Journals (Sweden)

    J.F.R. Robertson

    2014-09-01

    Full Text Available For many years, tamoxifen has been the _gold standard_ amongst anti-oestrogen therapies for breast cancer. However, the selective aro- matase inhibitors (AIs, anastrozole, letrozole and exemestane, have demonstrated advantages over tamoxifen as first-line treatments for advanced disease. Anastrozole is also more effective as an adjuvant treatment in early, operable breast cancer and is being increasingly used in the adjuvant setting. Generally, the selective oestrogen receptor modulators (SERMs, such as toremifene, droloxifene, idoxifene, ralox- ifene, and arzoxifene, show minimal activity in tamoxifen-resistant disease and show no superiority over tamoxifen as first-line treatments. In addition to these agents, other treatment options for advanced disease include high-dose oestrogens and progestins. Response rates for high- dose oestrogens and tamoxifen are similar, but the use of oestrogens is limited by their toxicity profile. Consequently, there is a need for new endocrine treatment options for breast cancer, particularly for use in disease that is resistant to tamoxifen or AIs. Fulvestrant (_Faslodex_ is a new type of steroidal oestrogen receptor (ER antagonist that downregulates cellular levels of the ER and progesterone receptor and has no agonist activity. This paper reviews the key efficacy and tolerability data for fulvestrant in postmenopausal women in the context of other endocrine therapies and explores the potential role of fulvestrant within the sequencing of endocrine therapies for advanced breast cancer.

  18. Canine mammary tumours, an overview.

    Science.gov (United States)

    Sleeckx, N; de Rooster, H; Veldhuis Kroeze, E J B; Van Ginneken, C; Van Brantegem, L

    2011-12-01

    Canine mammary tumours (CMTs) are the most common neoplasms in intact female dogs. Although the prevalence of these tumours decreases in regions where preventive ovari(ohyster)ectomy is performed, it remains an important disease entity in veterinary medicine. Moreover, treatment options are limited in comparison with human breast cancer. Nevertheless, recent human treatment protocols might have potential in bitches suffering from CMTs. PMID:21645126

  19. Vaccination with p53-peptide-pulsed dendritic cells, of patients with advanced breast cancer: report from a phase I study

    DEFF Research Database (Denmark)

    Svane, Inge Marie; Pedersen, Anders E; Johnsen, Hans E;

    2004-01-01

    Peptides derived from over-expressed p53 protein are presented by class I MHC molecules and may act as tumour-associated epitopes. Due to the diversity of p53 mutations, immunogenic peptides representing wild-type sequences are preferable as a basis for a broad-spectrum p53-targeting cancer vaccine....... Our preclinical studies have shown that wild-type p53-derived HLA-A2-binding peptides are able to activate human T cells and that the generated effector T cells are cytotoxic to human HLA-A2+, p53+ tumour cells. In this phase I pilot study, the toxicity and efficacy of autologous dendritic cells (DCs......) loaded with a cocktail of three wild-type and three modified p53 peptides are being analysed in six HLA-A2+ patients with progressive advanced breast cancer. Vaccinations were well tolerated and no toxicity was observed. Disease stabilisation was seen in two of six patients, one patient had a transient...

  20. 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.

  1. Pertuzumab, Trastuzumab, and Paclitaxel Albumin-Stabilized Nanoparticle Formulation in Treating Patients With HER2-Positive Advanced Breast Cancer

    Science.gov (United States)

    2016-06-23

    HER2-positive Breast Cancer; Recurrent Breast Cancer; Stage IIA Breast Cancer; Stage IIB Breast Cancer; Stage IIIA Breast Cancer; Stage IIIB Breast Cancer; Stage IIIC Breast Cancer; Stage IV Breast Cancer; Breast Adenocarcinoma; Inflammatory Breast Carcinoma

  2. Provision of a simplified methodology for determining estradiol and progesterone receptors in human breast tumours. Internal and external quality control

    International Nuclear Information System (INIS)

    A simplified assay for the detection of progesterone receptors (PR) in human breast tissue is described. Tissue storage is at -20 deg. C rather than -70 deg. C and a centrifugation speed of 20,000 rpm avoids requirement of an ultracentrifuge. Cytosol preparations obtained from homogenized oestradiol benzoate primed wistar rat uteri performed satisfactorily as positive controls with stability of two months in liquid nitrogen. The use of iodinated tracer (progesterone 11 alpha glucuronide 125 I iodotyramine) proved disappointing in the progesterone receptor assay in contrast to 125I oestradiol which worked well in a oestrogen receptor assay, previously developed. Hydroxyl-apatite was a better separating agent than dextran coated charcoal in both assays and yielded better sensitivity, particularly when protein concentrations were low. Five breast cancer specimens assayed yielded, by Scatchard analysis, Kd values between 12 to 22x10-9 m|h, comparable to the positive controls. However, two of these had binding site capacity of less than 5 fmol/mg cytosol as compared to the three others and the positive controls where values ranged from 47-196 fmol/mg cytosol. 28 refs, 6 figs, 14 tabs

  3. Management of advanced breast cancer with the epothilone B analog, ixabepilone

    Directory of Open Access Journals (Sweden)

    William Gradishar

    2009-06-01

    Full Text Available William GradisharRobert H Lurie Comprehensive Cancer Center, Northwestern University Feinberg School of Medicine, Chicago, IL, USAAbstract: Despite the activity of standard chemotherapies in advanced breast cancer, disease progression remains inevitable. Most patients exposed to anthracyclines and taxanes develop resistance and a significant subset shows primary resistance. The increasing use of these agents as adjuvant therapy may result in more anthracycline- and taxane-resistant patients in the metastatic setting; few treatment options are available for patients with metastatic breast cancer (MBC resistant to multiple chemotherapies. The heterogeneity of breast cancer represents another therapeutic challenge. Breast cancers may be classified as luminal, human epidermal growth factor 2 (HER2-positive, or estrogen receptor-, progesterone receptor-, and human epidermal growth factor 2-negative (ER/PR/HER2-negative, triple negative. HER2-positive and ER/PR/HER2-negative tumors are associated with poor prognosis owing to aggressive disease and poor long-term response to therapy. The epothilone B analog ixabepilone has low susceptibility to multiple mechanisms of resistance and has demonstrated activity in patients with MBC resistant to anthracyclines, taxanes, and/or capecitabine. Ixabepilone is the first epothilone to be approved, as monotherapy or in combination with capecitabine, for treatment of resistant/refractory MBC or locally advanced breast cancer. Treatment with ixabepilone is an option for patients with ER/PR/HER2-negative or HER2-positive disease and/or primary resistance to taxanes.Keywords: breast cancer, drug resistance, epothilone, HER2-positive, ixabepilone, ER/PR/HER2-negative (triple negative

  4. Gemcitabine Based Combination Regimens for Treatment of Refractory Advanced Breast Cancer

    Institute of Scientific and Technical Information of China (English)

    CHE Li; DI Li-jun; SONG Guo-hong; JIA Jun; YU Jing; WANG Xiao-li; ZHU Yu-lin; JIANG Han-fang; LIANG Xu

    2008-01-01

    Objective:Anthracycline and taxane are the standard agents in combined chemotherapy of advanced breast cancer.However,when these agents based chemotherapy is failure,the selection of salvage regimen is still of problem.Gemcitabine,an active agent in both lung cancer and pancreas cancer,is demonstrated effective in breast caner.But there have been relatively less data of gemcitabine in anthracycline and/or taxane-resistant breast cancer.Therefore we employe this study to explore the efficacy and safety of gemcitabine based combination regimen in this population.Methods:From May 2002 to March 2006,28 patients with measurable lesion of advanced metastatic breast cancer who were resistant to prior anthracycline and taxane based chemotherapy were enrolled.Patients were treated with gemcitabine based combination chemotherapy with a median cycles of 3(range 2-6).Results:The overall response rate was 28.6%(8/28),with 1 CR(Complete response 3.5%)and 7 PRs(Partial response 25%).Stable disease was seen in 8 patients(28.6%)while disease progressed in 12 patiens(42.8%).The median time to progression was 4.5 m(range,2-23 m).The main toxicity included bone marrow depression,alopecia,mucositis and peripheral neurotoxicity.The grade 3 to 4 clinical adverse effect was leukopenia in 5 cases(17.9%)and thrombocytopenia in 8 cases(30%).Conclusion:Gemcitabine based combination regimens is feasible in anthracycline and taxane-resistant advanced breast cancer.The clinical response and TTP is acceptable with limited toxicity pattern.

  5. Phase I and pharmacological study of the farnesyltransferase inhibitor tipifarnib (Zarnestra®, R115777) in combination with gemcitabine and cisplatin in patients with advanced solid tumours

    OpenAIRE

    Siegel-Lakhai, W S; Crul, M; Zhang, S; Sparidans, R W; Pluim, D; Howes, A.; Solanki, B; Beijnen, J.H.; Schellens, J. H. M.

    2005-01-01

    This phase I trial was designed to determine the safety and maximum tolerated dose (MTD) of tipifarnib in combination with gemcitabine and cisplatin in patients with advanced solid tumours. Furthermore, the pharmacokinetics of each of these agents was evaluated. Patients were treated with tipifarnib b.i.d. on days 1–7 of each 21-day cycle. In addition, gemcitabine was given as a 30-min i.v. infusion on days 1 and 8 and cisplatin as a 3-h i.v. infusion on day 1. An interpatient dose-escalation...

  6. Anti-EGFR Therapy: Mechanism and Advances in Clinical Efficacy in Breast Cancer

    Directory of Open Access Journals (Sweden)

    John F. Flynn

    2009-01-01

    Full Text Available This review will focus on recent advances in the application of antiepidermal growth factor receptor (anti-EGFR for the treatment of breast cancer. The choice of EGFR, a member of the ErbB tyrosine kinase receptor family, stems from evidence pinpointing its role in various anti-EGFR therapies. Therefore, an increase in our understanding of EGFR mechanism and signaling might reveal novel targets amenable to intervention in the clinic. This knowledge base might also improve existing medical treatment options and identify research gaps in the design of new therapeutic agents. While the approved use of drugs like the dual kinase inhibitor Lapatinib represents significant advances in the clinical management of breast cancer, confirmatory studies must be considered to foster the use of anti-EGFR therapies including safety, pharmacokinetics, and clinical efficacy.

  7. Feasibility of breast conservation surgery in locally advanced breast cancer downstaged by neoadjuvant chemotherapy: A study in mastectomy specimens using simulation lumpectomy

    OpenAIRE

    Viswambharan Jaiganesh; Kadambari D; Iyengar Krishnan; Srinivasan K

    2005-01-01

    BACKGROUND : The response of locally advanced breast cancer (LABC) to neoadjuvant chemotherapy (NACT) offers these patients previously treated by mastectomy, the chance for breast conservation. AIM : This study aims to assess the feasibility of lumpectomy in patients with LABC treated by NACT, with residual tumor 5 cm. SETTINGS, DESIGN : Single group prospective study from August 2001 to June 2003 in a teaching hospital. MATERIALS AND METHODS : Thirty patients with LABC whose tumors reduced...

  8. Chemotherapy and survival in advanced breast cancer: the inclusion of doxorubicin in Cooper type regimens.

    OpenAIRE

    A'Hern, R P; Smith, I. E.; Ebbs, S R

    1993-01-01

    The value of the inclusion of doxorubicin hydrochloride (dox) in Cooper type regimens in advanced breast cancer was assessed by performing an overview employing summary statistics derived from published papers of randomised clinical trials comparing Cooper type regimens that contain dox with regimens in which dox was replaced by one or more compounds. Trials were selected which published data on survival, time to treatment failure and response rate. This study suggests that dox confers advant...

  9. Quality of life among advanced breast cancer patients with and without distant metastasis

    OpenAIRE

    Wyatt, G.; Sikorskii, A.; TAMKUS, D.; You, M

    2012-01-01

    This study presents the results of a secondary analysis of data collected during a trial of reflexology that aimed to improve health-related quality of life (HRQOL) among women with advanced breast cancer in treatment. A comparison of HRQOL (functioning, symptoms, spirituality) of those with (n = 298) and without (n = 87) distant metastasis is presented. Following the intake interview, 385 women were randomised to reflexology, lay foot manipulation or conventional care control, and were inter...

  10. Role of Scintimammography in Assessing the Response of Neoadjuvant Chemotherapy in Locally Advanced Breast Cancer

    OpenAIRE

    Trehan, Romeeta; Seam, Rajeev K; Manoj K. Gupta; Sood, Ashwani; Dimri, Kislay; Mahajan, Rohit

    2014-01-01

    Locally advanced breast cancer (LABC) is a common cancer in the developing countries. Neoadjuvant chemotherapy (NACT) is a very important step in the treatment of such tumors and hence that the disease can be down staged and made amenable for surgery. All the tumors do not respond to the therapy equally. Hence, it becomes very important to predict the response of chemotherapy in such cases. This study evaluated the role of scintimammography in assessing the response to NACT in 23 patients wit...

  11. Outcome of neoadjuvant chemotherapy in locally advanced breast cancer: A tertiary care centre experience

    OpenAIRE

    Tapesh Bhattacharyya; Suresh C Sharma; Budhi Singh Yadav; Rajinder Singh; Gurpreet Singh

    2014-01-01

    Background: Introduction of neoadjuvant chemotherapy (NACT) has dramatically changed the management of locally advanced breast cancer (LABC). However, very few randomized trials of NACT have been carried out specifically in LABC patients in our country. In this retrospective analysis, we presented our experience with NACT in LABC patients. Materials and Methods: Medical records of 148 patients of stage III LABC patients treated with NACT, followed by surgery and radiotherapy from January 2006...

  12. The clinical observation of neoadjuvant chemotherapy in locally advanced breast cancer with DX regimen

    Institute of Scientific and Technical Information of China (English)

    Miao Zhang; Jianing Qiu; Shuxian Qu; Yaling Han; Zhaozhe Liu; Xiaodong Xie

    2014-01-01

    Objective:The recent clinical curative ef ect and adverse events of docetaxel and capecitabine (DX) of neo-adjuvant chemotherapy in patients with local y advanced breast cancer was discussed. Methods:The data of 72 cases of neoadjuvant chemotherapy (DX) in local y advanced breast cancer after 4 cycles were retrospectively analyzed. Docetaxel 75 mg/m2 by infusion 1 h on d1, capecitabine 2000 mg/m2 by oral for twice daily on d1–14, 21 days was a cycle. Results:Al 72 patients were assessed for ef icacy and adverse events. The total ef ective rate was 80.5%(58/72), including pathological complete response (pCR) was 7 (9.7%), clinical complete remission (cCR) was 15(20.8%), clinical partial response (PR) was 43 (59.7%), stable disease (SD) was 8 (11.1%) and progressive disease (PD) was 6 (8.3%). The main adverse events were gastrointestinal reactions and bone marrow suppression. The 3 to 4 degrees of adverse reactions including granulocytopenia in 7 patients (20.6%), hand-foot syndrome in 6 patients (15.2%). Conclusion:The DX regimen provide a favorable ef icacy and safety profile in patients with local y advanced breast cancer for neoadjuvant chemotherapy.

  13. Clinical observation of capecitabine monotherapy in elderly patients with advanced breast cancer

    Institute of Scientific and Technical Information of China (English)

    Miao Zhang; Zhaozhe Liu Co-first author; Zhendong Zheng; Tao Han; Yaling Han; Min Song; Xiaodong Xie

    2015-01-01

    Objective The aim of the study was to evaluate the safety and ef icacy of capecitabine mono-chemo-therapy in elderly patients with advanced breast cancer. Methods The data from 36 cases of capecitabine monotherapy in elderly patients with advanced breast cancer were retrospectively analyzed. Oral administration of capecitabine 2000 mg/m2 twice daily (D1–14) for 21 days constituted a cycle. The ef ect of the disease and main adverse reactions were evaluated every 2 cycles. Results The data from 36 elderly patients were studied. The median number of chemotherapy cycles was 4. The total ef ective rate was 30.6% (11/36) and the disease control rate was 72.2% (26/36). The number of patients with clinical complete remission was 2, clinical partial response was 9, stable disease was 15, and progressive disease was 10. Where treatment was ef ective, the median time to progression was 6 months and the median overal survival was 9.5 months. The main adverse events were gastroin-testinal reactions, bone marrow suppression, and oral mucositis; most of the reactions were grade 1 to 2. Grade 3 to 4 adverse reactions included granulocytopenia in 2 patients (12.5%) and hand-foot syndrome in 1 patient (6.7%). Conclusion Capecitabine monotherapy was ef ective in control ing disease progression, and adverse reactions were tolerated by elderly patients with advanced breast cancer.

  14. Clinical observation on docetaxel plus S1 in the treatment of advanced metastatic breast cancer

    Institute of Scientific and Technical Information of China (English)

    Jian Cao; Ping Sun

    2013-01-01

    Objective: The aim of our study was to observe the efficacy and adverse reactions of docetaxel plus S1 in patients with advanced metastatic breast cancer. Methods: Twenty-seven patients with advanced metastatic breast cancer receiving docetaxel plus S1 in our hospital were analyzed. The efficacy and safety were evaluated according to RECIST and NCI CTC 3.0. Results: The clinical efficacy and toxicity were evaluated in all the 27 patients, including 1 case of CR, 12 of PR, 6 of SD, and 8 of PD (ORR = 48.1%, CBR = 70.3%). The median time to tumor progression (mTTP) was 7.3 months. No IV degree of adverse reaction was observed in the observation group. Most adverse reactions were degrees I and II, the most common reactions were neutropenia (59.3%), abnormal liver function (33.3%), gastrointestinal adverse events (29.6 %) and stomatitis (7.4%). Conclusion: With good efficacy and low toxicity, docetaxel plus S1 could be administered in the treatment of advanced metastatic breast cancer.

  15. Experience in treatment of patients with locally advanced or recurrent breast cancer. Intraarterial infusion chemotherapy combined with radiotherapy

    International Nuclear Information System (INIS)

    For the purpose of local control and breast conservation, intraarterial infusion chemotherapy combined with radiotherapy has been indicated in patients with locally advanced breast cancer both in primary and recurrent cases. The present series, evaluated during the past 4 years, consisted of 15 patients 35-83 years of age, with invasive ductal carcinoma, including 10 with primary breast cancer (stage IIIb: 1, IV: 9) and 5 with postoperative recurrence (stage IIIb: 2, IV: 3). Intraarterial chemotherapy is started, basically infusing ADM 50 mg, MMC 10 mg and CDDP 50 mg into the internal thoracic and/or subclavian artery 1-3 times, followed by reduction surgery (quadrantectomy: 4, wide resection: 2) and radiotherapy to the breast, supraclavicular, parasternal and cervical regions according to tumor extent. Local response after arterial infusion was CR: 2, PR: 10, NC: 3 (response rate: 73% ). The response rate of distant metastases after arterial infusion was 73%. Of 10 patients with primary breast cancer, recurrence was noted in 1. Breast conservation was successful in 8 of 10 patients. One of them, in stage IIIb, has survived for 4.5 years with no evidence of disease and with breast conservation. Five patients with postoperative recurrence showed CR with no recurrence after intraarterial chemotherapy and radiotherapy. Acute skin reaction occurred in 6 patients, and was especially frequent in patients with postoperative recurrence (4 of 5). According to these results, combined therapy affords breast conservation even in patients with locally advanced breast cancer, and improves patient's QOL in stage IV. (author)

  16. 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

  17. MRI EVALUATION OF SUPRATENTORIAL TUMOURS

    Directory of Open Access Journals (Sweden)

    Shruti

    2016-01-01

    Full Text Available Brain tumours represents 1.7% of all cancers and contributes 1.8% of all cancer deaths. Of all the brain tumours 80% are supratentorial.1 Magnetic Resonance Imaging is an important modality, having higher sensitivity for detecting intracranial pathology. Multiplanar imaging is possible with MRI which helps in detection, localization and characterization of the lesion. The MRI examination has helped in early diagnosis, accurate localization of the tumour with prompt initiation of appropriate medical or surgical therapy. Recent advances like Magnetic Resonance (MR spectroscopy, MR fluoroscopy with stereotactic guided biopsy have revolutionized the role of MRI in study of intracranial tumours.

  18. Tumour lysis syndrome: A rare acute presentation of locally advanced testicular cancer – Case report and review of literature

    Directory of Open Access Journals (Sweden)

    Marcus Chow

    2016-01-01

    Full Text Available Tumour lysis syndrome (TLS is a potentially fatal complication of malignancy or its treatment. This uncommon syndrome comprises laboratory findings of hyperuricaemia, hypocalcaemia, hyperkalaemia and hyperphosphataemia. A literature search revealed a total of eight patients, with testicular cancer, who had TLS. All these patients had metastatic disease. We present a unique case of a 47-year-old gentleman we saw in clinic, who presented with a rapidly growing right groin mass and acute breathlessness, and discuss the diagnosis and management of TLS. TLS is extremely rare in testicular cancer but necessitates the awareness of urologists. TLS can occur spontaneously in testicular malignancy. Cell lysis in a rapidly proliferating germ cell tumour is a possible mechanism. The prompt identification and institution of management for TLS is crucial to improve clinical outcomes.

  19. An implantable and controlled drug-release silk fibroin nanofibrous matrix to advance the treatment of solid tumour cancers.

    Science.gov (United States)

    Xie, Maobin; Fan, Dejun; Chen, Yufeng; Zhao, Zheng; He, Xiaowen; Li, Gang; Chen, Aizheng; Wu, Xiaojian; Li, Jiashen; Li, Zhi; Hunt, John A; Li, Yi; Lan, Ping

    2016-10-01

    The development of more effective cancer therapeutic strategies are still critically required. The maximization of the therapeutic effect in combination with avoiding the severe side effects on normal tissues when using chemotherapy drugs is still an urgent problem that requires improvements urgently. Here we provide implantable and controllable drug-release that utilises silk fibroin (SF) as a nanofibrous drug delivery system (DDS) for cancer treatment. A nanofibrous structure with controllable fibre diameter (curcumin (CM)-SF nanofibrous matrix had a superior anti-cancer potential when the concentration was >5 μg/mL. The mechanism could be explained by the cell cycle being held in the S phase. The toxic effect on normal cells (NCM460) was minimized by using a treatment concentration range (5-20 μg/mL). Implantation of this DDS into the tumour site inhibited the growth of solid tumour; this offers an alternative approach for novel cancer therapy. PMID:27376557

  20. Impact of group psychotherapy in chemotherapy induced vomiting for treatment of advanced breast and lungs cancer

    International Nuclear Information System (INIS)

    To assess the effect of group psychotherapy in the management of the side effects of chemotherapy treatment in advanced breast and lung cancer. One hundred patients treated with chemotherapy for advanced stage (IIIB and IV) breast and lung cancer were selected with ECOG performance status of 0 or 1. All patients received anti-emetic medications half an hour before chemotherapy. All those patients in this category who completed fist line chemotherapy with 6 cycles were included. Fifty were subjected to group discussions with other patients, family members and medical staff. This was labeled group A. The other 50 were not included in group discussion and were labeled group B. Both the group received similar standard chemotherapy and pre-medication for vomiting as per their disease and chemotherapy schedule. Breast and lung cancer patients were 29 and 21 in each arm respectively. At the end of the discharge, grade 2 and above of vomiting, according to common terminology criteria for adverse events (CTCAE) was counted for all patients in both the arms A and B, over full length of treatment for 6 cycles, and then were compared statistically. Mean with standard deviation for adverse event (vomiting) in group A and B was 6.2 + 2.6 and 13.4 + 3.8 respectively per cycle of treatment. It was observed that group psychotherapy had statistically significant effect (p-value <0.05) on the management of vomiting. Group psychotherapy can be used to reduce the incidence of vomiting in advanced breast and lung cancer patients treated with chemotherapy. (author)

  1. High risk factors of brain metastases in 295 patients with advanced breast cancer

    Institute of Scientific and Technical Information of China (English)

    YAN Min; L(U) Hui-min; LIU Zhen-zhen; LIU Hui; ZHANG Meng-wei; SUN Xi-bin; CUI Shu-de

    2013-01-01

    Background The incidence of brain metastases in patients with breast cancer is approximately 10%-16%,and survival after diagnosis of brain metastases is usually short.This study was designed to evaluate the risk factors associated with brain metastases in advanced breast cancer patients,with a view to help predict patient groups with high risk of brain metastases.Methods In total,295 patients with advanced breast cancer were evaluated.All patients were pathologically confirmed and metastatic lesions were confirmed pathologically or by imaging.All patients were examined at least once every 6 months with head CT or MRI.Patients showing symptoms underwent immediate inspection,and brain metastatic lesions were confirmed by head CT and/or MRI.Results At a median follow-up of 12 months from the occurrence of metastases,brain metastases had occurred in 49 patients (16.6%).In our univariate analysis,variables significantly related to increased risk of brain metastases were hormone receptor-negative tumors,epidermal growth factor receptor 2 (HER2)-positive tumors,and multiple distant metastases.Patients with dominant tumor sites in soft tissue,or defined as Luminal A subtype,tended to have a lower risk of brain metastases than patients with visceral metastases,Luminal B subtype,triple-negative subtype or HER2-enriched subtype tumors.Conclusions Our results strongly suggest that factors such as Luminal B,triple-negative,and HER2-enriched subtypes are high risk factors for brain metastases.These data,therefore,provide pivotal clinical evidence towards a comprehensive understanding of the risk factors of brain metastases in advanced breast cancer patients.

  2. Colloidal stability, surface characterisation and intracellular accumulation of Rhodium(II) citrate coated superparamagnetic iron oxide nanoparticles in breast tumour: a promising platform for cancer therapy

    International Nuclear Information System (INIS)

    The colloidal stability of a rhodium(II) citrate, Rh2(H2cit)4, coating on the surface of maghemite (γ-Fe2O3) nanoparticles was studied and compared in different dispersion media. The adsorption of Rh2(H2cit)4 at the water-maghemite interface was evaluated as a function of pH and complex concentration. A slight pH-dependent adsorption of the complex was observed with a maximum at pH 3. The colloidal stability of the functionalised nanoparticles with different amounts of Rh2(H2cit)4 as a function of pH was evaluated using dynamic light scattering measurements. The particles have a mean magnetic core size of 5.6 nm and the hydrodynamic diameters are approximately 60 nm, which remained unchanged in the pH range in which the samples were a stable sol. The tolerance to different dispersion media, which were deionised water, saline, phosphate-buffered saline (PBS), foetal bovine serum (FBS) and NaCl solutions with different concentrations, was investigated. At moderate ionic strength, the colloidal stability of the dispersions was similar in saline and in PBS compared to the stability of dispersions diluted in water. Moreover, the intracellular accumulation of nanoparticles in 4T1 breast tumour was examined by ultrastructural analysis performed by transmission electron microscopy. The rhodium(II) citrate-coated nanoparticles were found mostly in the cytoplasm and nucleus. Thus, we suggest that these SPIO nanoparticles functionalized with Rh2(H2Cit)4 can be potential tools for anticancer therapy.

  3. Colloidal stability, surface characterisation and intracellular accumulation of Rhodium(II) citrate coated superparamagnetic iron oxide nanoparticles in breast tumour: a promising platform for cancer therapy

    Energy Technology Data Exchange (ETDEWEB)

    Silva Nunes, Eloiza da [Universidade Federal de Goias, Campus Samambaia, Instituto de Quimica (Brazil); Lemos Brettas Carneiro, Marcella; Guirelli Simoes de Oliveira, Ricardo; Nair Bao, Sonia [Universidade de Brasilia (UnB), Instituto de Ciencias Biologicas (Brazil); Ribeiro de Souza, Aparecido, E-mail: ardsouza@quimica.ufg.br [Universidade Federal de Goias, Campus Samambaia, Instituto de Quimica (Brazil)

    2013-06-15

    The colloidal stability of a rhodium(II) citrate, Rh{sub 2}(H{sub 2}cit){sub 4}, coating on the surface of maghemite ({gamma}-Fe{sub 2}O{sub 3}) nanoparticles was studied and compared in different dispersion media. The adsorption of Rh{sub 2}(H{sub 2}cit){sub 4} at the water-maghemite interface was evaluated as a function of pH and complex concentration. A slight pH-dependent adsorption of the complex was observed with a maximum at pH 3. The colloidal stability of the functionalised nanoparticles with different amounts of Rh{sub 2}(H{sub 2}cit){sub 4} as a function of pH was evaluated using dynamic light scattering measurements. The particles have a mean magnetic core size of 5.6 nm and the hydrodynamic diameters are approximately 60 nm, which remained unchanged in the pH range in which the samples were a stable sol. The tolerance to different dispersion media, which were deionised water, saline, phosphate-buffered saline (PBS), foetal bovine serum (FBS) and NaCl solutions with different concentrations, was investigated. At moderate ionic strength, the colloidal stability of the dispersions was similar in saline and in PBS compared to the stability of dispersions diluted in water. Moreover, the intracellular accumulation of nanoparticles in 4T1 breast tumour was examined by ultrastructural analysis performed by transmission electron microscopy. The rhodium(II) citrate-coated nanoparticles were found mostly in the cytoplasm and nucleus. Thus, we suggest that these SPIO nanoparticles functionalized with Rh{sub 2}(H{sub 2}Cit){sub 4} can be potential tools for anticancer therapy.

  4. Genomic and mutational profiling of ductal carcinomas in situ and matched adjacent invasive breast cancers reveals intra-tumour genetic heterogeneity and clonal selection

    Science.gov (United States)

    Lambros, Maryou B; Campion-Flora, Adriana; Rodrigues, Daniel Nava; Gauthier, Arnaud; Cabral, Cecilia; Pawar, Vidya; Mackay, Alan; A’Hern, Roger; Marchiò, Caterina; Palacios, Jose; Natrajan, Rachael; Weigelt, Britta; Reis-Filho, Jorge S

    2016-01-01

    The mechanisms underlying the progression from ductal carcinoma in situ (DCIS) to invasive ductal carcinoma (IDC) of the breast are yet to be fully elucidated. Several hypotheses have been put forward to explain the progression from DCIS to IDC, including the selection of a subpopulation of cancer cells with specific genetic aberrations, the acquisition of new genetic aberrations or non-genetic mechanisms mediated by the tumour microenvironment. To determine whether synchronously diagnosed ipsilateral DCIS and IDCs have modal populations with distinct repertoires of gene copy number aberrations and mutations in common oncogenes, matched frozen samples of DCIS and IDCs were retrieved from 13 patients and subjected to microarray-based comparative genomic hybridisation (aCGH), and Sequenom MassARRAY (Oncocarta v1.0 panel). Fluorescence in situ hybridisation and Sanger sequencing were employed to validate the aCGH and Sequenom findings, respectively. Although the genomic profiles of matched DCIS and IDCs were similar, in three of 13 matched pairs amplification of distinct loci (i.e. 1q41, 2q24.2, 6q22.31, 7q11.21, 8q21.2 and 9p13.3) was either restricted to, or more prevalent in, the modal population of cancer cells of one of the components. Sequenom MassARRAY identified PIK3CA mutations restricted to the DCIS component in two cases, and in a third case, the frequency of the PIK3CA mutant allele reduced from 49% in the DCIS to 25% in the IDC component. Despite the genomic similarities between synchronous DCIS and IDC, our data provide strong circumstantial evidence to suggest that in some cases the progression from DCIS to IDC is driven by the selection of non-modal clones that harbour a specific repertoire of genetic aberrations. PMID:22252965

  5. Consensus Recommendations for Advancing Breast Cancer: Risk Identification and Screening in Ethnically Diverse Younger Women

    Directory of Open Access Journals (Sweden)

    Alexander Stojadinovic, Thomas A Summers, John Eberhardt, Albert Cerussi, Warren Grundfest, Charles M. Peterson, Michael Brazaitis, Elizabeth Krupinski, Harold Freeman

    2011-01-01

    Full Text Available A need exists for a breast cancer risk identification paradigm that utilizes relevant demographic, clinical, and other readily obtainable patient-specific data in order to provide individualized cancer risk assessment, direct screening efforts, and detect breast cancer at an early disease stage in historically underserved populations, such as younger women (under age 40 and minority populations, who represent a disproportionate number of military beneficiaries. Recognizing this unique need for military beneficiaries, a consensus panel was convened by the USA TATRC to review available evidence for individualized breast cancer risk assessment and screening in young (< 40, ethnically diverse women with an overall goal of improving care for military beneficiaries. In the process of review and discussion, it was determined to publish our findings as the panel believes that our recommendations have the potential to reduce health disparities in risk assessment, health promotion, disease prevention, and early cancer detection within and in other underserved populations outside of the military. This paper aims to provide clinicians with an overview of the clinical factors, evidence and recommendations that are being used to advance risk assessment and screening for breast cancer in the military.

  6. Advanced Imaging and Receipt of Guideline Concordant Care in Women with Early Stage Breast Cancer

    Science.gov (United States)

    Buist, Diana S. M.; Gold, Laura S.; Zeliadt, Steven; Hunter Merrill, Rachel; Etzioni, Ruth; Ramsey, Scott D.; Sullivan, Sean D.; Kessler, Larry

    2016-01-01

    Objective. It is unknown whether advanced imaging (AI) is associated with higher quality breast cancer (BC) care. Materials and Methods. Claims and Surveillance Epidemiology and End Results data were linked for women diagnosed with incident stage I-III BC between 2002 and 2008 in western Washington State. We examined receipt of preoperative breast magnetic resonance imaging (MRI) or AI (defined as computed tomography [CT]/positron emission tomography [PET]/PET/CT) versus mammogram and/or ultrasound (M-US) alone and receipt of guideline concordant care (GCC) using multivariable logistic regression. Results. Of 5247 women, 67% received M-US, 23% MRI, 8% CT, and 3% PET/PET-CT. In 2002, 5% received MRI and 5% AI compared to 45% and 12%, respectively, in 2008. 79% received GCC, but GCC declined over time and was associated with younger age, urban residence, less comorbidity, shorter time from diagnosis to surgery, and earlier year of diagnosis. Breast MRI was associated with GCC for lumpectomy plus radiation therapy (RT) (OR 1.55, 95% CI 1.08–2.26, and p = 0.02) and AI was associated with GCC for adjuvant chemotherapy for estrogen-receptor positive (ER+) BC (OR 1.74, 95% CI 1.17–2.59, and p = 0.01). Conclusion. GCC was associated with prior receipt of breast MRI and AI for lumpectomy plus RT and adjuvant chemotherapy for ER+ BC, respectively. PMID:27525122

  7. Specific efficacy of peptide receptor radionuclide therapy with {sup 177}Lu-octreotate in advanced neuroendocrine tumours of the small intestine

    Energy Technology Data Exchange (ETDEWEB)

    Sabet, Amir; Dautzenberg, Kristina; Haslerud, Torjan; Aouf, Anas; Sabet, Amin; Biersack, Hans-Juergen [University Hospital, Department of Nuclear Medicine, Bonn (Germany); Simon, Birgit [University Hospital, Department of Radiology, Bonn (Germany); Mayer, Karin [University Hospital, Department of Internal Medicine and Oncology, Bonn (Germany); Ezziddin, Samer [University Hospital, Department of Nuclear Medicine, Bonn (Germany); Saarland University, Department of Nuclear Medicine, Homburg (Germany)

    2015-07-15

    Increasing evidence supports the value of peptide receptor radionuclide therapy (PRRT) in patients with metastatic neuroendocrine tumours (NET), but there are limited data on its specific efficacy in NET of small intestinal (midgut) origin. This study aims to define the benefit of PRRT with {sup 177}Lu-octreotate for this circumscribed entity derived by a uniformly treated patient cohort. A total of 61 consecutive patients with unresectable, advanced small intestinal NET G1-2 stage IV treated with {sup 177}Lu-octreotate (4 intended cycles at 3-month intervals, mean activity per cycle 7.9 GBq) were analysed. Sufficient tumour uptake on baseline receptor imaging and either documented tumour progression (n = 46) or uncontrolled symptoms (n = 15) were prerequisites for treatment. Response was evaluated according to modified Southwest Oncology Group (SWOG) criteria and additionally with Response Criteria in Solid Tumors (RECIST) 1.1. Assessment of survival was performed using Kaplan-Meier curves and Cox proportional hazards model for uni- and multivariate analyses. Toxicity was assessed according to standardized follow-up laboratory work-up including blood counts, liver and renal function, supplemented with serial {sup 99m}Tc-diethylenetriaminepentaacetic acid (DTPA) clearance measurements. The median follow-up period was 62 months. Reversible haematotoxicity (≥ grade 3) occurred in five patients (8.2 %). No significant nephrotoxicity (≥ grade 3) was observed. Treatment response according to modified SWOG criteria consisted of partial response in 8 (13.1 %), minor response in 19 (31.1 %), stable disease in 29 (47.5 %) and progressive disease in 5 (8.2 %) patients. The disease control rate was 91.8 %. Median progression-free survival (PFS) and overall survival (OS) was 33 [95 % confidence interval (CI) 25-41] and 61 months (95 % CI NA), respectively. Objective response was associated with longer survival (p = 0.005). Independent predictors of shorter PFS were

  8. PR-104 a bioreductive pre-prodrug combined with gemcitabine or docetaxel in a phase Ib study of patients with advanced solid tumours

    Directory of Open Access Journals (Sweden)

    McKeage Mark J

    2012-10-01

    Full Text Available Abstract Background The purpose of this phase Ib clinical trial was to determine the maximum tolerated dose (MTD of PR-104 a bioreductive pre-prodrug given in combination with gemcitabine or docetaxel in patients with advanced solid tumours. Methods PR-104 was administered as a one-hour intravenous infusion combined with docetaxel 60 to 75 mg/m2 on day one given with or without granulocyte colony stimulating factor (G-CSF on day two or administrated with gemcitabine 800 mg/m2 on days one and eight, of a 21-day treatment cycle. Patients were assigned to one of ten PR-104 dose-levels ranging from 140 to 1100 mg/m2 and to one of four combination groups. Pharmacokinetic studies were scheduled for cycle one day one and 18F fluoromisonidazole (FMISO positron emission tomography hypoxia imaging at baseline and after two treatment cycles. Results Forty two patients (23 females and 19 males were enrolled with ages ranging from 27 to 85 years and a wide range of advanced solid tumours. The MTD of PR-104 was 140 mg/m2 when combined with gemcitabine, 200 mg/m2 when combined with docetaxel 60 mg/m2, 770 mg/m2 when combined with docetaxel 60 mg/m2 plus G-CSF and ≥770 mg/m2 when combined with docetaxel 75 mg/m2 plus G-CSF. Dose-limiting toxicity (DLT across all four combination settings included thrombocytopenia, neutropenic fever and fatigue. Other common grade three or four toxicities included neutropenia, anaemia and leukopenia. Four patients had partial tumour response. Eleven of 17 patients undergoing FMISO scans showed tumour hypoxia at baseline. Plasma pharmacokinetics of PR-104, its metabolites (alcohol PR-104A, glucuronide PR-104G, hydroxylamine PR-104H, amine PR-104M and semi-mustard PR-104S1, docetaxel and gemcitabine were similar to that of their single agents. Conclusions Combination of PR-104 with docetaxel or gemcitabine caused dose-limiting and severe myelotoxicity, but prophylactic G-CSF allowed PR-104 dose escalation with docetaxel. Dose

  9. Clinical outcome of hyperthermo-radio-chemotherapy combined with surgery for patients with advanced breast cancer

    Energy Technology Data Exchange (ETDEWEB)

    Kobayashi, Kokuriki; Fujimoto, Shigeru; Takahashi, Makoto; Nemoto, Kazuhisa; Mutou, Takaaki; Toyosawa, Tadashi [Social Insurance Funabashi Central Hospital, Chiba (Japan)

    2001-09-01

    For the patients with breast cancer that are locally advanced or metastatic, treatment to control not only local disease but also distant metastasis is desirable. Hyperthermo-radio-chemotherapy (HRC) combined with surgery was performed for 16 patients with stage III or stage IV breast cancer and the clinical outcomes of this multimodal treatment were analyzed. The size of the primary tumor was significantly reduced after preoperative HRC with the CR rate of 18.8% (3/16) and PR rate of 81.3% (13/16). Three- and 5-year overall survival rates for the stage III patients were 100% and 87.5%, respectively; their 3- and 5- year disease free rates were 78.8% and 52.5%, respectively. One- and 3-year survival rates for the stage IV patients were 80.0% and 20.0%, respectively. No loco-regional recurrence was observed. HRC combined with surgery for advanced breast cancer patients was effective for down-staging of the primary tumor and maintaining local control. (author)

  10. Paclitaxel Albumin-Stabilized Nanoparticle Formulation in Treating Older Patients With Locally Advanced or Metastatic Breast Cancer

    Science.gov (United States)

    2016-02-09

    Male Breast Cancer; Recurrent Breast Cancer; Stage IV Breast Cancer; Estrogen Receptor-negative Breast Cancer; Estrogen Receptor-positive Breast Cancer; HER2-negative Breast Cancer; HER2-positive Breast Cancer; Progesterone Receptor-negative Breast Cancer; Progesterone Receptor-positive Breast Cancer; Stage IIIA Breast Cancer; Stage IIIB Breast Cancer; Stage IIIC Breast Cancer; Triple-negative Breast Cancer

  11. Locally advanced non inflammatory breast cancer treated by combined chemotherapy and preoperative irradiation: updated results in a series of 120 patients; Cancer du sein localement evolue non inflammatoire traite par association de chimiotherapie et de radiotherapie a dose preoperatoire: reactualisation des resultats d'une serie de 120 patientes

    Energy Technology Data Exchange (ETDEWEB)

    Lerouge, D.; Touboul, E.; Moureau-Zabotto, L. [Hopital Tenon AP-HP, Service d' oncologie-radiotherapie, 75 - Paris (France); Lefran, J.P.; Blondon, J. [Hopital Pitie-Salpetriere AP-HP, Service de chirurgie generale et gynecologique, 75 - Paris (France); Genestie, C. [Hopital Pitie-Salpetriere AP-HP, Service d' anatomopathologie, 75 - Paris (France)

    2004-06-01

    Purpose. - To evaluate our updated data concerning survival and locoregional control in a study of locally advanced non inflammatory breast cancer after primary chemotherapy followed by external preoperative irradiation. Patients and methods. - Between 1982 and 1998, 120 patients (75 stage IIIA, 41 stage IIIB, and 4 stage IIIC according to AJCC staging system 2002) were consecutively treated by four courses of induction chemotherapy with anthracycline-containing combinations followed by preoperative irradiation (45 Gy to the breast and nodal areas) and a fifth course of chemotherapy. Three different locoregional approaches were proposed, depending on tumour characteristics and tumour response. After completion of local therapy, all patients received a sixth course of chemotherapy and a maintenance adjuvant chemotherapy regimen without anthracycline. The median follow-up from the beginning of treatment was 140 months. Results. - Mastectomy and axillary dissection were performed in 49 patients (with residual tumour larger than 3 cm in diameter or located behind the nipple or with bifocal tumour), and conservative treatment in 71 patients (39 achieved clinical complete response or partial response >90% and received additional radiation boost to initial tumour bed; 32 had residual mass {<=}3 cm in diameter and were treated by wide excision and axillary dissection followed by a boost to the excision site). Ten-year actuarial local failure rate was 13% after irradiation alone, 23% after wide excision and irradiation, and 4% after mastectomy (p =0.1). After multivariate analysis, possibility of breast-conserving therapy was related to initial tumour size (<6 vs. {>=}6 cm in diameter, p =0.002). Ten-year overall metastatic disease-free survival rate was 61%. After multivariate analysis, metastatic disease-free survival rates were significantly influenced by clinical stage (stage IIIA-B vs. IIIC, p =0.0003), N-stage (N0 vs. N1-2a, and 3c, p = 0.017), initial tumour size (<6

  12. Outcome of peptide receptor radionuclide therapy with {sup 177}Lu-octreotate in advanced grade 1/2 pancreatic neuroendocrine tumours

    Energy Technology Data Exchange (ETDEWEB)

    Ezziddin, Samer; Khalaf, Feras; Vanezi, Maria; Haslerud, Torjan; Zreiqat, Abdullah Al; Biersack, Hans-Juergen; Sabet, Amir [University Hospital Bonn, Department of Nuclear Medicine, Bonn (Germany); Mayer, Karin [University Hospital, Department of Internal Medicine and Oncology, Bonn (Germany); Willinek, Winfried [University Hospital, Department of Radiology, Bonn (Germany)

    2014-05-15

    The clinical benefit of peptide receptor radionuclide therapy (PRRT) in patients with pancreatic neuroendocrine tumours (pNET) has not yet been well described and defined in its full extent due to limited data in this tumour subgroup. This study was intended to obtain robust, comparative data on the outcome and toxicity of standardized PRRT with {sup 177}Lu-octreotate in a well-characterized population of patients with advanced pNET of grade 1/2 (G1/2). We retrospectively analysed a cohort of 68 pNET patients with inoperable metastatic disease consecutively treated with {sup 177}Lu-octreotate (four intended cycles at 3-monthly intervals; mean activity per cycle 8.0 GBq). Of these 68 patients, 46 (67.6 %) had documented morphological tumour progression during the 12 months before initiation of treatment, and PRRT was the first-line systemic therapy in 35 patients (51.5 %). Response was evaluated according to modified Southwest Oncology Group (SWOG) criteria and additionally with Response Criteria in Solid Tumors (RECIST) 1.1. Survival was analysed using Kaplan-Meier curves and Cox proportional hazards model for univariate and multivariate analyses. Toxicity was assessed by standard follow-up laboratory work-up including blood count, and liver and renal function, supplemented with serial {sup 99m}Tc-DTPA clearance measurements. The median follow-up period was 58 months (range 4 - 112). Reversible haematotoxicity (grade 3 or more) occurred in four patients (5.9 %). No significant nephrotoxicity (grade 3 or more) was observed. Treatment responses (SWOG criteria) consisted of a partial response in 41 patients (60.3 %), a minor response in 8 (11.8 %), stable disease in 9 (13.2 %), and progressive disease in 10 (14.7 %). Median progression-free survival (PFS) and overall survival (OS) were 34 (95 % CI 26 - 42) and 53 months (95 % CI 46 - 60), respectively. A G1 proliferation status was associated with longer PFS (p = 0.04) and OS (p = 0.044) in the multivariate analysis

  13. Noninvasive Characterization of Locally Advanced Breast Cancer Using Textural Analysis of Quantitative Ultrasound Parametric Images

    Directory of Open Access Journals (Sweden)

    Hadi Tadayyon

    2014-12-01

    Full Text Available PURPOSE: The identification of tumor pathologic characteristics is an important part of breast cancer diagnosis, prognosis, and treatment planning but currently requires biopsy as its standard. Here, we investigated a noninvasive quantitative ultrasound method for the characterization of breast tumors in terms of their histologic grade, which can be used with clinical diagnostic ultrasound data. METHODS: Tumors of 57 locally advanced breast cancer patients were analyzed as part of this study. Seven quantitative ultrasound parameters were determined from each tumor region from the radiofrequency data, including mid-band fit, spectral slope, 0-MHz intercept, scatterer spacing, attenuation coefficient estimate, average scatterer diameter, and average acoustic concentration. Parametric maps were generated corresponding to the region of interest, from which four textural features, including contrast, energy, homogeneity, and correlation, were determined as further tumor characterization parameters. Data were examined on the basis of tumor subtypes based on histologic grade (grade I versus grade II to III. RESULTS: Linear discriminant analysis of the means of the parametric maps resulted in classification accuracy of 79%. On the other hand, the linear combination of the texture features of the parametric maps resulted in classification accuracy of 82%. Finally, when both the means and textures of the parametric maps were combined, the best classification accuracy was obtained (86%. CONCLUSIONS: Textural characteristics of quantitative ultrasound spectral parametric maps provided discriminant information about different types of breast tumors. The use of texture features significantly improved the results of ultrasonic tumor characterization compared to conventional mean values. Thus, this study suggests that texture-based quantitative ultrasound analysis of in vivo breast tumors can provide complementary diagnostic information about tumor histologic

  14. 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.

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

    International Nuclear Information System (INIS)

    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. 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. 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

  16. 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.

  17. Molecular pathology of breast apocrine carcinomas

    DEFF Research Database (Denmark)

    Celis, J.E.; Gromova, I.; Gromov, P.;

    2006-01-01

    Breast cancer is a heterogeneous disease that encompasses a wide range of histopathological types including: invasive ductal carcinoma, lobular carcinoma, medullary carcinoma, mucinous carcinoma, tubular carcinoma, and apocrine carcinoma among others. Pure apocrine carcinomas represent about 0...... between benign apocrine changes and breast carcinoma is unclear and has been a matter of discussion for many years. Recent proteome expression profiling studies of breast apocrine macrocysts, normal breast tissue, and breast tumours have identified specific apocrine biomarkers [15-hydroxyprostaglandin...... dehydrogenase (15-PGDH) and hydroxymethylglutaryl coenzyme A reductase (HMG-CoA reductase)] present in early and advanced apocrine lesions. These biomarkers in combination with proteins found to be characteristically upregulated in pure apocrine carcinomas (psoriasin, S100A9, and p53) provide a protein...

  18. Recombinant erythropoietin for the anaemia of patients with advanced Gastrointestinal Stromal Tumours (GIST receiving imatinib: an active agent only in non progressive patients

    Directory of Open Access Journals (Sweden)

    Duffaud Florence

    2012-09-01

    Full Text Available Abstract Recombinant erythropoietin for the anaemia of patients with advanced Gastrointestinal Stromal Tumours (GIST receiving imatinib : an active agent only in non progressive patients. Background Imatinib is a standard treatment for advanced/metastatic GIST and in adjuvant setting. Anaemia is frequently observed in patients with advanced GIST, and is one of the most frequent side effects of imatinib with grade 3–4 anaemia in 10% of patients. Whether EPO treatment is useful in the management of GIST patients receiving imatinib treatment is unknown. Methods A retrospective study of EPO treatment in GIST patients receiving imatinib was undertaken in 4 centres. Thirty four patients received EPO treatment among the 319 GIST patients treated with imatinib in clinical trials or with compassionate use between 2001 and 2003. The efficacy of EPO on the anaemia of patients with GIST treated with imatinib was analyzed. Results There were 18 males and 16 females with a median age of 59 years. Median WHO-PS was 1. Primary tumour sites were mainly gastric (32% and small bowel (29%. Sites of metastases were mainly liver (82% and peritoneum (79%. The median delay between the initiation of imatinib treatment and EPO was 58 days (range 0–553. Median haemoglobin (Hb level prior to EPO was 9 g/dL (range 6,9-11,8 and 11,7 g/dL (range 6,8-14,4 after 2 months. An increase of more than 2 g/dL was observed in 18 (53% of patients. None of the 7 patients who progressed (PD under imatinib treatment (400 mg/day experienced HB response, as compared to 66% (18/27 of the remaining patients (PR + SD (p = 0,002. Primary tumour site, liver metastases, peritoneal metastases, age, gender did not correlate with HB response to EPO. Response to EPO was observed in 2/11 patients receiving high-dose imatinib (800 mg/day vs 16/23 of others. Using logistic regression, only PD before EPO treatment was retained as a predictive factor for EPO response. Conclusion EPO enables to

  19. Role of {sup 18}FDG PET/CT in patients treated with {sup 177}Lu-DOTATATE for advanced differentiated neuroendocrine tumours

    Energy Technology Data Exchange (ETDEWEB)

    Severi, Stefano; Sansovini, Maddalena; Ianniello, Annarita; Matteucci, Federica [Cancer Institute of Romagna (IRST), Unit of Radiometabolic Medicine, Meldola, FC (Italy); Nanni, Oriana; Scarpi, Emanuela [Cancer Institute of Romagna (IRST), Unit of Biostatistics and Clinical Trials, Meldola, FC (Italy); Bodei, Lisa; Gilardi, Laura; Paganelli, Giovanni [European Institute of Oncology, Division of Nuclear Medicine, Milan (Italy); Nicoletti, Stefania [Cancer Institute of Romagna (IRST), Unit of Medical Oncology, Meldola, FC (Italy)

    2013-06-15

    The prognostic value of FDG PET for neuroendocrine tumours (NETs) has been reported. In this study we evaluated the role of FDG PET in predicting response and progression-free survival (PFS) after {sup 177}Lu-DOTATATE peptide receptor radionuclide therapy (Lu-PRRT) in patients with advanced well-differentiated grade 1/2 NETs. We retrospectively evaluated 52 patients with progressive advanced NETs overexpressing somatostatin receptors and treated with Lu-PRRT with a cumulative activity up to 27.7 GBq divided into five courses. According to WHO 2010/ENETS classification, patients were stratified into two groups: those with grade 1 tumour (Ki-67 index {<=}2 %, 19 patients), and those with grade 2 tumour (Ki-67 index >3 % to <20 %, 33 patients). On the basis of the FDG PET scan, 33 patients were classified as PET-positive (PET+) and 19 as PET-negative (PET-). FDG PET was positive in 57 % of patients with grade 1 NET and in 66 % of patients with grade 2 NET, and the rates of disease control (DC, i.e. complete response + partial response + stable disease) in grade 1 and grade 2 patients were 95 % and 79 %, respectively (P = 0.232). In PET- and PET+ patients, the DC rates were 100 % and 76 % (P = 0.020) with a PFS of 32 and 20 months, respectively (P = 0.033). Of the PET+ patients with grade 1 NET, 91 % showed disease control, whereas about one in three PET+ patients with grade 2 NET (32 %) progressed after Lu-PRRT (DC rate 68 %). These results suggest that FDG PET evaluation is useful for predicting response to Lu-PRRT in patients with grade 1/2 advanced NETs. Notably, none of PET- patients had progressed at the first follow-up examination after Lu-PRRT. Grade 2 NET and PET+ (arbitrary SUV cutoff >2.5) were frequently associated with more aggressive disease. PET+ patients with grade 2 NET, 32 % of whom did not respond to Lu-PRRT monotherapy, might benefit from more intensive therapy protocols, such as the combination of chemotherapy and PRRT. (orig.)

  20. Relative microvessel area of the primary tumour, and not lymph node status, predicts the presence of bone marrow micrometastases detected by reverse transcriptase polymerase chain reaction in patients with clinically non-metastatic breast cancer

    International Nuclear Information System (INIS)

    About 50% of patients with breast cancer have no involvement of axillary lymph nodes at diagnosis and can be considered cured after primary locoregional treatment. However, about 20–30% will experience distant relapse. The group of patients at risk is not well characterised: recurrence is probably due to the establishment of micrometastases before treatment. Given the early steps of metastasis in which tumour cells interact with endothelial cells of blood vessels, and, given the independent prognostic value in breast cancer of both the quantification of tumour vascularisation and the detection of micrometastases in the bone marrow, the aim of this study was to determine the relationship between vascularisation, measured by Chalkley morphometry, and the bone marrow content of cytokeratin-19 (CK-19) mRNA, quantified by real-time reverse transcriptase polymerase chain reaction, in a series of 68 patients with localised untreated breast cancer. The blood concentration of factors involved in angiogenesis (interleukin-6 and vascular endothelial growth factor) and of factors involved in coagulation (D-dimer, fibrinogen, platelets) was also measured. When bone marrow CK-19 relative gene expression (RGE) was categorised according to the cut-off value of 0.77 (95th centile of control patients), 53% of the patients had an elevated CK-19 RGE. Patients with bone marrow micrometastases, on the basis of an elevated CK-19 RGE, had a mean Chalkley count of 7.5 ± 1.7 (median 7, standard error [SE] 0.30) compared with a mean Chalkley count of 6.5 ± 1.7 in other patients (median 6, SE 0.3) (Mann–Whitney U-test; P = 0.04). Multiple regression analysis revealed that Chalkley count, not lymph node status, independently predicted CK-19 RGE status (P = 0.04; odds ratio 1.38; 95% confidence interval 1.009–1.882). Blood parameters reflecting angiogenesis and coagulation were positively correlated with Chalkley count and/or CK-19 RGE. Our data are in support of an association between

  1. Quality of life among advanced breast cancer patients with and without distant metastasis.

    Science.gov (United States)

    Wyatt, G; Sikorskii, A; Tamkus, D; You, M

    2013-03-01

    This study presents the results of a secondary analysis of data collected during a trial of reflexology that aimed to improve health-related quality of life (HRQOL) among women with advanced breast cancer in treatment. A comparison of HRQOL (functioning, symptoms, spirituality) of those with (n = 298) and without (n = 87) distant metastasis is presented. Following the intake interview, 385 women were randomised to reflexology, lay foot manipulation or conventional care control, and were interviewed again at weeks 5 and 11. Those with distant metastasis were older, had fewer comorbid conditions, and a smaller proportion were employed. Longitudinal analysis of HRQOL at intake, 5 and 11 weeks revealed that those with distant metastasis had lower functioning and more pain; however, no differences were found on fatigue, nausea, shortness of breath, sleep quality, anxiety, depressive symptoms or spirituality. Despite advanced disease, 56% of all women in this study were below the clinical screening cut-off for depressive symptoms. These findings may indicate that patients with advanced breast cancer have adapted emotionally and spiritually; however, the management of physical symptoms remains a priority. PMID:23252474

  2. Chronic thyroiditis in patients with advanced breast carcinoma: metabolic and morphologic changes on PET-CT

    Energy Technology Data Exchange (ETDEWEB)

    Tateishi, Ukihide [University of Texas, MD Anderson Cancer Center, Department of Nuclear Medicine, Houston, TX (United States); Yokohama City University Graduate School of Medicine, Department of Radiology, Yokohama (Japan); University of Texas MD Anderson Cancer Center, Division of Diagnostic Imaging, Houston, TX (United States); Gamez, Cristina; Yeung, Henry W.D.; Macapinlac, Homer A. [University of Texas, MD Anderson Cancer Center, Department of Nuclear Medicine, Houston, TX (United States); Dawood, Shaheenah; Cristofanilli, Massimo [University of Texas, MD Anderson Cancer Center, Division of Breast Medical Oncology, Houston, TX (United States); Inoue, Tomio [Yokohama City University Graduate School of Medicine, Department of Radiology, Yokohama (Japan)

    2009-06-15

    To investigate clinical implications of FDG uptake in the thyroid glands in patients with advanced breast carcinoma by comparing metabolic and morphologic patterns on positron emission tomography (PET)/computed tomography (CT). The institutional review board waived the requirement for informed consent. A retrospective analysis was performed in 146 women (mean age 54 years) with advanced breast carcinoma who received systemic treatment. All patients underwent PET-CT before and after treatment. All PET-CT studies were reviewed in consensus by two reviewers. Morphologic changes including volume and mean parenchymal density of the thyroid glands were evaluated. Maximum standardized uptake value (SUVmax) and total lesion glycolysis (TLG) were determined to evaluate metabolic changes. These parameters were compared between patients with chronic thyroiditis who received thyroid hormone replacement therapy and those who did not. Of the 146 patients, 29 (20%) showed bilaterally diffuse uptake in the thyroid glands on the baseline PET-CT scan. The SUVmax showed a linear relationship with volume (r = 0.428, p = 0.021) and the mean parenchymal density (r = -0.385, p = 0.039) of the thyroid glands. In 21 of the 29 patients (72%) with hypothyroidism who received thyroid hormone replacement therapy, the volume, mean parenchymal density, SUVmax, and TLG of the thyroid glands showed no significant changes. In contrast, 8 of the 29 patients (28%) who did not receive thyroid hormone replacement therapy showed marked decreases in SUVmax and TLG. Diffuse thyroid uptake on PET-CT represents active inflammation caused by chronic thyroiditis in patients with advanced breast carcinoma. Diffuse thyroid uptake may also address the concern about subclinical hypothyroidism which develops into overt disease during follow-up. (orig.)

  3. Experimental tumour treatment

    International Nuclear Information System (INIS)

    This report of 1984 is the seventh in a series and presents that year's results of continuous studies in the domain of experimental tumour radiotherapy. In the year under review, more personnel has been available for the studies, and the scientific programmes for the assessment of acute and chronic side effects of radiotherapies have been extended. New models have been developed, among them a first system based on animal experiments, for quantifying the mucositis of the oral and pharyngeal mucosa, a limiting condition in the radiotherapy of head and throat tumours. Another significant advancement is a model for quantification of chronical damage to the ureter, which still is a serious problem in the radiotherapy of gynaecological tumours. The 1984 experimental tumour studies have been mainly devoted to the repopulation and split-dose recovery in various tumours, concentrating on dose fractionation as one of the major problems studies. Particular interest has been attached to the processes involved in treatments over several weeks with a daily effective dose of 2 Gy. (orig./MG)

  4. 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

  5. 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)

    The aim of this retrospective study was to determine if some features of baseline 18F-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 18F-FDG PET images. The parameters extracted included SUVmax, SUVmean, 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 18F-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 18F-FDG uptake than T2 tumours (AUC <0.75), whereas there were no significant differences in SUVmax and SUVmean. Invasive ductal carcinoma showed higher SUVmax 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 SUVmax 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, SUVmax, SUVmean and TLG significantly differed among the three phenotype subgroups (HER2-positive, triple-negative and ER-positive/HER2

  6. Scintigraphic evaluation of functional hepatic mass in patients with advanced breast cancer.

    OpenAIRE

    Virgolini, I; Kornek, G; Höbart, J; Li, S R; Raolerer, M.; Bergmann, H; Scheithauer, W.; Pantev, T.; Angelberger, P.; Sinzinger, H.

    1993-01-01

    Recent studies suggest a high specificity of 99mTc-galactosyl neoglycoalbumin (99mTc-NGA) receptor scanning in vivo by providing both morphological and functional diagnosis of liver disease. In 22 patients with advanced breast cancer 99mTc-NGA (150 MBq; 50 nmol) was exclusively trapped by the liver, the images showing 'cold spots' in areas of liver metastases formation. A two-tailed analysis was performed: the time activity curves recorded for the liver and precordial area were subjected to a...

  7. Endocrine therapy for hormone treatment-naïve advanced breast cancer.

    Science.gov (United States)

    Martin, Miguel; Lopez-Tarruella, Sara; Gilarranz, Yolanda Jerez

    2016-08-01

    A proportion of patients with hormone receptor-positive locally advanced or metastatic breast cancer will not have received prior endocrine therapy. However, there are limited clinical data specifically in these patients. We conducted a review of randomized phase II and III clinical studies of anastrozole, letrozole, exemestane, palbociclib, and fulvestrant to determine the evidence base supporting use of specific endocrine therapies in this patient population. From our findings, there is a paucity of clinical studies in patients with endocrine therapy-naïve disease; however, it appears that first-line treatment effects are consistent between patients who have and have not received prior endocrine treatment. PMID:27326977

  8. Pathological predictive factors for tumor response in locally advanced breast carcinomas treated with anthracyclin-based neoadjuvant chemotherapy

    OpenAIRE

    Trupti Patel; Anuja Gupta; Manoj Shah

    2013-01-01

    Aim: Neoadjuvant chemotherapy (NACT) is used as a primary treatment for locally advanced breast carcinoma (LABC) and also extended to operable breast cancer. The aim of this study was to evaluate the predictive value of different histological parameters in core biopsy of LABC patients treated with anthracycline-based chemotherapy regimen. Pathological assessment of the excised tumor bed is the gold standard and is essential for identifying the group of patients with pathologic complete respon...

  9. Surgery for Breast Cancer

    Science.gov (United States)

    ... Next Topic Breast-conserving surgery (lumpectomy) Surgery for breast cancer Most women with breast cancer have some type ... Relieve symptoms of advanced cancer Surgery to remove breast cancer There are two main types of surgery to ...

  10. 6.3 MeV fast neutrons in the treatment of patients with locally advanced and locally recurrent breast cancer

    Science.gov (United States)

    Velikaya, V. V.; Musabaeva, L. I.; Lisin, V. A.; Startseva, Zh. A.

    2016-08-01

    The study included 135 breast cancer patients (70 patients with locally recurrent breast cancer and 65 patients with locally advanced breast cancer with unfavorable prognostic factors) who received the neutron therapy alone or in combination with the photon therapy. The neutron therapy was shown to be effective in multimodality treatment of patients with locally advanced and locally recurrent breast cancer. The 8-year survival rate in patients without repeated breast cancer recurrence was 87.6 ± 8.7% after the neutron and neutron-photon therapy and 54.3 ± 9.2% after the electron beam therapy.

  11. IMPACT OF SEQUENTIAL NEOADJUVANT CHEMOTHERAPY IN LOCALLY ADVANCED BREAST CANCER: A SERIES OF 10 CASES

    Directory of Open Access Journals (Sweden)

    Gopa

    2014-04-01

    Full Text Available Breast cancer currently is a major health problem among women worldwide accounting for around 13.7% cancer deaths, nearly 1/3rd of it being due to Locally advanced breast cancer (LABC. Despite progress achieved in diagnosis & therapy of Breast cancer, LABC remains a major clinical challenge and in efforts to increase pCR, CCR & DFS in LABC, Neoadjuvant or primary chemotherapy followed by locoregional therapy and adjuvant systemic CT is well accepted treatment strategy since last 3 decades. Further to address the issue of drug resistance in NACT sequential anthracycline-taxane NACT has been evaluated by many researchers and has resulted in better outcome in terms of overall survival and pCR. In this study we have evaluated 4 cycles of sequential anthracycline-taxane, 2 cycles of Cyclophosphamide, Epirubicin, Fluracil +2 cycles of Docetaxel, Epirubicin (CEF- DE NACT in a series of 10 cases of ER/PR +ve, Her -2 neu negative patients of LABC. 9/10 cases were rendered operable after primary chemotherapy and were subjected to further 4 cycles of adjuvant chemotherapy (1 cycle CEF, 1 cycle DE, 2cycles single agent Docetaxel, followed by locoregional RT. This tailored sequential NACT protocol in our subgroup of patient was well tolerated, well accepted and resulted in substantial increase in operability with CCR & DFS in 6/10 cases on 3 years follow up and pCR in one patient. Sequential NACT needs further validation by more RCT with extensive follow up

  12. Delay in referring and related factors in patients with advanced breast cancer - Emam Hospital (2000

    Directory of Open Access Journals (Sweden)

    "Ghaem Maghami F

    2002-07-01

    Full Text Available Background: The aim of study was to determine the frequency of delay referring and related factors in patients with advanced breast cancer, in Imam Khomeini Hospital in the 2000. Materials and Methods: Successively 200 patients were entered the study if they were consentient. A questionnaire was constructed and information was obtained through interviewing. Results: From the cases, 64 patients (32 percent referred without delay and 136 patients (68 percent referred tardily. The patients who were late in comparison with patients who didn’t late, had significantly higher mean age (P=0.004, lower education level (P=0.002, and lower economic status (P=0.001. The frequency rate of single were lower among them (P=0.001, fewer percent were residual of big cities (P=0.01 and they had less rate of available physician (P=0.004. 24.3 percent of delay referring patients and 53.1 percent of patients without delay has a positive family history of breast cancer (P=0.001. 62.5 percent of delay referring patients and 85 percent of patients without delay were aware about importance of Self Breast Examination (S.B.E (P=0.002 and respectively 84.4 percent and 98.4 percent were award about symptoms of breast cancer (P=0.01. 23.5 percent and 33 percent of patients with and without delay Knew the method of B.S.E respectively. It wasn’t a significant difference. Conclusion: Lack of awareness about necessity of medical consultation, fear, carelessly, unavailable physician and poverty were the major causes of delay in patients who referred late.

  13. Somatostatin receptor expression, tumour response, and quality of life in patients with advanced hepatocellular carcinoma treated with long-acting octreotide.

    Science.gov (United States)

    Cebon, J; Findlay, M; Hargreaves, C; Stockler, M; Thompson, P; Boyer, M; Roberts, S; Poon, A; Scott, A M; Kalff, V; Garas, G; Dowling, A; Crawford, D; Ring, J; Basser, R; Strickland, A; Macdonald, G; Green, M; Nowak, A; Dickman, B; Dhillon, H; Gebski, V

    2006-10-01

    Octreotide may extend survival in hepatocellular carcinoma (HCC). Forty-one per cent of HCCs have high-affinity somatostatin receptors. We aimed to determine the feasibility, safety, and activity of long-acting octreotide in advanced HCC; to identify the best method for assessing somatostatin receptor expression; to relate receptor expression to clinical outcomes; and to evaluate toxicity. Sixty-three patients with advanced HCC received intramuscular long-acting octreotide 20 mg monthly until progression or toxicity. Median age was 67 years (range 28-81 years), male 81%, Child-Pugh A 83%, and B 17%. The aetiologies of chronic liver disease were alcohol (22%), viral hepatitis (44%), and haemochromatosis (6%). Prior treatments for HCC included surgery (8%), chemotherapy (2%), local ablation (11%), and chemoembolisation (6%). One patient had an objective partial tumour response (2%, 95% CI 0-9%). Serum alpha-fetoprotein levels decreased more than 50% in four (6%). Median survival was 8 months. Thirty four of 61 patients (56%) had receptor expression detected by scintigraphy; no clear relationship with clinical outcomes was identified. There were few grade 3 or 4 toxicities: hyperglycaemia (8%), hypoglycaemia (2%), diarrhoea (5%), and anorexia (2%). Patients reported improvements in some symptoms, but no major changes in quality of life were detected. Long-acting octreotide is safe in advanced HCC. We found little evidence of anticancer activity. A definitive randomised trial would identify whether patients benefit from this treatment in other ways. PMID:16953241

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

    International Nuclear Information System (INIS)

    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)

  15. Recombinant leukocyte A interferon in advanced breast cancer. Results of a phase II efficacy trial.

    Science.gov (United States)

    Sherwin, S A; Mayer, D; Ochs, J J; Abrams, P G; Knost, J A; Foon, K A; Fein, S; Oldham, R K

    1983-05-01

    Nineteen patients with advanced refractory metastatic breast cancer no longer responsive to chemotherapy were treated in the first phase II efficacy trial of recombinant leukocyte A interferon (IFL-rA), a highly purified single molecular species of alpha interferon prepared by recombinant DNA methods. Patients received a previously determined maximum tolerated dose for this agent (50 X 10(6) U/m2 body surface area) by intramuscular injection three times weekly for up to 3 months. The symptoms of toxicity observed in this trial resemble those previously reported for alpha interferons and include fever, chills, fatigue, anorexia, and leukopenia. All patients required dose reductions, most often for reasons of severe fatigue. Of the 17 patients evaluable for tumor response, one patient had stable disease and 16 had evidence of tumor progression. We conclude that IFL-rA is not an active agent in the treatment of advanced, refractory breast cancer when used at a maximum tolerated dose on this treatment schedule. PMID:6342490

  16. Retrospective Analysis of Locally Advanced Noninflammatory Breast Cancer From Chennai, South India, 1990-1999

    International Nuclear Information System (INIS)

    Purpose: This was a retrospective observational study to elicit the outcome of the therapeutic strategy of concurrent neoadjuvant chemoradiotherapy protocol for locally advanced breast cancer. Methods and Materials: A large series of 1,117 consecutive cases of locally advanced breast cancer treated at the Cancer Institute (WIA), in Chennai, South India, between 1990 and 1999 and followed through 2004 formed the basis for this study. Disease-free survival was the main outcome, and nodal and tumor downstaging were the intermediate outcome measures studied. Results: Primary tumor downstaging was observed in 45% and nodal downstaging in 57.5%. The disease-free survival rate of nodal downstaged patients at 5, 10, and 15 years was 75%, 65%, and 58%, respectively. The corresponding rates for pre- and postoperative node-negative patients were 70%, 60%, and 59%. The best survival was seen among those who were tumor and node negative postoperatively. Nodal downstaging halved the risk of disease recurrence and death compared with node positivity, irrespective of tumor sterility. Conclusions: A randomized trial using cyclophosphamide, methotrexate, and 5-fluorouracil vs. an anthracycline-based regimen in the setting of concurrent chemoradiotherapy appears indicated. Additional preoperative chemotherapy to maximize nodal and tumor downstaging should be investigated. A change in postoperative chemotherapy according to nodal status could also be explored

  17. Breast Cancer Clinical Trials: Past Half Century Moving Forward Advancing Patient Outcomes.

    Science.gov (United States)

    Kuerer, Henry M; van la Parra, Raquel F D

    2016-10-01

    Clinical trials in breast cancer have contributed immensely to the advancements of modern multimodal breast cancer treatment. Due to improved screening methods and more effective biologic-based tailored systemic therapies, the extent of surgery necessary for local and systemic control of disease is decreasing. Sequential trials for ductal carcinoma in situ (DCIS) have changed the management of this disease and are culminating in randomized active surveillance studies in an effort potentially to prevent overtreatment of low- and intermediate-grade disease. For patients with initial node-positive disease, clipping and marking of the biopsy-proven nodal metastases before the start of neoadjuvant chemotherapy can allow for selective node dissection based on the axillary response. With the current advances in primary systemic therapy, feasibility trials are beginning to investigate the potential of nonoperative therapy for invasive cancers with percutaneously documented pathologic complete response. This article presents a review and update on landmark clinical trials related to DCIS, the extent of axillary surgery in node-positive disease, and the integration of systemic therapy with local therapy. PMID:27364503

  18. The distribution of trace elements Ca, Fe, Cu and Zn and the determination of copper oxidation state in breast tumour tissue using {mu}SRXRF and {mu}XANES

    Energy Technology Data Exchange (ETDEWEB)

    Farquharson, M J; Al-Ebraheem, A [Department of Radiography, City Community and Health Sciences, City University, London, EC1V 0HB (United Kingdom); Falkenberg, G [Hamburger Synchrotronstrahlungslabor at Deutsches Elektronen-Synchrotron, DESY, Notkestr. 85, D-22603, Hamburg (Germany); Leek, R; Harris, A L [Cancer Research UK, Oxford Cancer Centre, Molecular Oncology Laboratories, University of Oxford, Weatherall Institute of Molecular Medicine, John Radcliffe Hospital, Oxford, 0X3 9DS (United Kingdom); Bradley, D A [Department of Physics, University of Surrey, Guildford, Surrey, GU2 7XH (United Kingdom)], E-mail: m.j.farquharson@city.ac.uk

    2008-06-07

    A micro beam synchrotron x-ray fluorescence ({mu}SRXRF) technique has been used to determine the localization of metals in primary invasive ductal carcinoma of breast. Nine samples were examined, all of which were formalin fixed tissues arranged as micro arrays of 1.0 mm diameter and 10 {mu}m thickness. Cu was the particular interest in this study although 2D maps of the elements Ca, Fe and Zn, which are also of physiological importance, are presented. The distribution of these metals was obtained at approximately 18 {mu}m spatial resolution and compared with light transmission images of adjacent sections that were H and E stained to reveal the location of the cancer cell clusters. Correlations were found between these reference images and the elemental distributions indicating an increase in all element concentrations in the tumour regions of all samples, with the exception of Fe, which in some cases showed a reverse of this trend. On average over all samples the percentage difference from the normal tissue elemental concentrations are Ca {approx} 67%, Cu {approx} 64% and Zn {approx} 145%. Micro x-ray absorption near edge spectroscopy ({mu}XANES) was used to estimate the oxidation state of Cu in 19 normal and 17 tumour regions spread over five samples. The shape and the position of both normal and tumour regions suggest that they contain mixtures of copper ions with a significant fraction of Cu{sup 2+}. However, the shape of the spectra does not exclude the presence of Cu{sup +}. Tumour regions were found to have a higher fraction of Cu{sup +} compared to the normal samples.

  19. The distribution of trace elements Ca, Fe, Cu and Zn and the determination of copper oxidation state in breast tumour tissue using μSRXRF and μXANES

    International Nuclear Information System (INIS)

    A micro beam synchrotron x-ray fluorescence (μSRXRF) technique has been used to determine the localization of metals in primary invasive ductal carcinoma of breast. Nine samples were examined, all of which were formalin fixed tissues arranged as micro arrays of 1.0 mm diameter and 10 μm thickness. Cu was the particular interest in this study although 2D maps of the elements Ca, Fe and Zn, which are also of physiological importance, are presented. The distribution of these metals was obtained at approximately 18 μm spatial resolution and compared with light transmission images of adjacent sections that were H and E stained to reveal the location of the cancer cell clusters. Correlations were found between these reference images and the elemental distributions indicating an increase in all element concentrations in the tumour regions of all samples, with the exception of Fe, which in some cases showed a reverse of this trend. On average over all samples the percentage difference from the normal tissue elemental concentrations are Ca ∼ 67%, Cu ∼ 64% and Zn ∼ 145%. Micro x-ray absorption near edge spectroscopy (μXANES) was used to estimate the oxidation state of Cu in 19 normal and 17 tumour regions spread over five samples. The shape and the position of both normal and tumour regions suggest that they contain mixtures of copper ions with a significant fraction of Cu2+. However, the shape of the spectra does not exclude the presence of Cu+. Tumour regions were found to have a higher fraction of Cu+ compared to the normal samples

  20. Concurrent chemo-radiotherapy following neoadjuvant chemotherapy in locally advanced breast cancer

    Directory of Open Access Journals (Sweden)

    Zinser-Sierra Juan

    2009-07-01

    Full Text Available Abstract Background Despite broad advances in multimodal treatment of locally advanced breast cancer (LABC, 30 to 40% of patients develop loco-regional relapse. The aim of this study was to analyze in a retrospective manner the effectiveness of concurrent chemo-radiotherapy (CCRTh after neoadjuvant chemotherapy (NCT in patients with LABC. Methods One hundred twelve patients with LABC (stage IIB-IIIB were treated with NCT (5-fluorouracil 500 mg/m2, doxorubicin 50 mg/m2, and cyclophosphamide 500 mg/m2 (FAC, or doxorubicin 50 mg/m2 and cyclophosphamide 500 mg/m2 (AC IV in four 21-day courses followed by CCRTh (60 Gy breast irradiation and weekly mitomycin 5 mg/m2, 5-fluorouracil 500 mg/m2, and dexamethasone 16 mg, or cisplatin 30 mg/m2, gemcitabine 100 mg/m2 and dexamethasone 16 mg, and 6–8 weeks later, surgery and two additional courses of FAC, AC, or paclitaxel 90 mg/m2 weekly for 12 weeks, and in case of estrogen-receptor positive patients, hormonal therapy. Results Stages IIB, IIIA and -B were 21.4, 42.9, and 35.7%, respectively. Pathological complete response (pCR in the breast was 42% (95% CI, 33.2–50.5% and, 29.5% (95% CI, 21.4–37.5% if including both the breast and the axillary nodes. Multivariate analysis showed that the main determinant of pCR was negative estrogen-receptor status (HR = 3.8; 95% CI, 1.5–9; p = 0.016. The 5-year disease-free survival (DFS was 76.9% (95% CI, 68.2–84.7%. No relationship between pCR and DFS was found. Multivariate analysis demonstrated that the main DFS determinant was clinical stage (IIB and IIIA vs. IIIB, HR = 3.1; 95% CI, 1.02–9.74; p = 0.04. Only one patient had local recurrence. Five-year overall survival was 84.2% (95% CI, 75–93.2%. The toxicity profile was acceptable. Conclusion This non-conventional multimodal treatment has good loco-regional control for LABC. Randomized clinical trials of preoperative CCRTh following chemotherapy, in patients with LABC are warranted.

  1. Concurrent chemo-radiotherapy following neoadjuvant chemotherapy in locally advanced breast cancer

    International Nuclear Information System (INIS)

    Despite broad advances in multimodal treatment of locally advanced breast cancer (LABC), 30 to 40% of patients develop loco-regional relapse. The aim of this study was to analyze in a retrospective manner the effectiveness of concurrent chemo-radiotherapy (CCRTh) after neoadjuvant chemotherapy (NCT) in patients with LABC. One hundred twelve patients with LABC (stage IIB-IIIB) were treated with NCT (5-fluorouracil 500 mg/m2, doxorubicin 50 mg/m2, and cyclophosphamide 500 mg/m2 (FAC), or doxorubicin 50 mg/m2 and cyclophosphamide 500 mg/m2 (AC) IV in four 21-day courses) followed by CCRTh (60 Gy breast irradiation and weekly mitomycin 5 mg/m2, 5-fluorouracil 500 mg/m2, and dexamethasone 16 mg, or cisplatin 30 mg/m2, gemcitabine 100 mg/m2 and dexamethasone 16 mg), and 6–8 weeks later, surgery and two additional courses of FAC, AC, or paclitaxel 90 mg/m2 weekly for 12 weeks, and in case of estrogen-receptor positive patients, hormonal therapy. Stages IIB, IIIA and -B were 21.4, 42.9, and 35.7%, respectively. Pathological complete response (pCR) in the breast was 42% (95% CI, 33.2–50.5%) and, 29.5% (95% CI, 21.4–37.5%) if including both the breast and the axillary nodes. Multivariate analysis showed that the main determinant of pCR was negative estrogen-receptor status (HR = 3.8; 95% CI, 1.5–9; p = 0.016). The 5-year disease-free survival (DFS) was 76.9% (95% CI, 68.2–84.7%). No relationship between pCR and DFS was found. Multivariate analysis demonstrated that the main DFS determinant was clinical stage (IIB and IIIA vs. IIIB, HR = 3.1; 95% CI, 1.02–9.74; p = 0.04). Only one patient had local recurrence. Five-year overall survival was 84.2% (95% CI, 75–93.2%). The toxicity profile was acceptable. This non-conventional multimodal treatment has good loco-regional control for LABC. Randomized clinical trials of preoperative CCRTh following chemotherapy, in patients with LABC are warranted

  2. A new human breast cancer cell line, KPL-3C, secretes parathyroid hormone-related protein and produces tumours associated with microcalcifications in nude mice.

    OpenAIRE

    Kurebayashi, J; Kurosumi, M.; Sonoo, H

    1996-01-01

    Parathyroid hormone-related protein (PTHrP) is the main cause of humoral hypercalcaemia of malignancy (HHM). We recently established a new human breast cancer cell line, designated KPL-3C, from the malignant effusion of a breast cancer patient with HHM. Morphological, cytogenetic and immunohistochemical analyses indicated that the cell line is derived from human breast cancer. The KPL-3C cells stably secrete immunoreactive PTHrP measured by a two-site immunoradiometric assay, possess both oes...

  3. Surgery and radiation therapy of triple-negative breast cancers: From biology to clinics.

    Science.gov (United States)

    Bernier, Jacques; Poortmans, Philip M P

    2016-08-01

    Triple negative breast cancer refers to tumours lacking the expression of the three most used tumour markers, namely oestrogen receptors, progesterone receptors, and human epidermal growth factor receptor 2 (HER2). These cancers are known to carry a more dismal prognosis than the other molecular subtypes. Whether a more aggressive local-regional treatment is warranted or not in patients with triple-negative breast cancer is still a matter of debate. Indeed there remain a number of grey zones with respect to the optimization of the extent and the timing of surgery and radiation therapy (RT) in this patient population, also in consideration of the significant heterogeneity in biological behaviour and response to treatment identified for these tumours. The objective of this review is to provide an insight into the biological and clinical behaviour of triple-negative breast cancers and revisit the most recent advances in their management, focussing on local-regional treatments. PMID:27318170

  4. Differential oxidative status and immune characterization of the early and advanced stages of human breast cancer.

    Science.gov (United States)

    Panis, C; Victorino, V J; Herrera, A C S A; Freitas, L F; De Rossi, T; Campos, F C; Simão, A N Colado; Barbosa, D S; Pinge-Filho, P; Cecchini, R; Cecchini, A L

    2012-06-01

    Breast cancer is the malignant neoplasia with the highest incidence in women worldwide. Chronic oxidative stress and inflammation have been indicated as major mediators during carcinogenesis and cancer progression. Human studies have not considered the complexity of tumor biology during the stages of cancer advance, limiting their clinical application. The purpose of this study was to characterize systemic oxidative stress and immune response parameters in early (ED; TNM I and II) and advanced disease (AD; TNM III and IV) of patients diagnosed with infiltrative ductal carcinoma breast cancer. Oxidative stress parameters were evaluated by plasmatic lipoperoxidation, carbonyl content, thiobarbituric reactive substances (TBARS), nitric oxide levels (NO), total radical antioxidant parameter (TRAP), superoxide dismutase, and catalase activities and GSH levels. Immune evaluation was determined by TNF-α, IL-1β, IL-12, and IL-10 levels and leukocytes oxidative burst evaluation by chemiluminescence. Tissue damage analysis included heart (total CK and CKMB), liver (AST, ALT, GGT), and renal (creatinine, urea, and uric acid) plasmatic markers. C-reactive protein (CRP) and iron metabolism were also evaluated. Analysis of the results verified different oxidative stress statuses occur at distinct cancer stages. ED was characterized by reduction in catalase, 8-isoprostanes, and GSH levels, with enhanced lipid peroxidation and TBARS levels. AD exhibited more pronounced oxidative status, with reduction in catalase activity and TRAP, intense lipid peroxidation and high levels of NO, TBARs, and carbonyl content. ED patients presented a Th2 immune pattern, while AD exhibited Th1 status. CRP levels and ferritin were increased in both stages of disease. Leukocytes burst impairment was observed in both the groups. Plasma iron levels were significantly elevated in AD. The data obtained indicated that oxidative stress enhancement and immune response impairment may be necessary to ensure

  5. Tumour regression grading after chemoradiotherapy for locally advanced rectal cancer: A near pathologic complete response does not translate into good clinical outcome

    International Nuclear Information System (INIS)

    Background: After preoperative chemoradiotherapy (CRT) for rectal cancer, clinically undetectable residual tumour deposits or pathologic lymph nodes may remain in the mesorectum. Aim: The aim of this study was to report histopathological effects of CRT and factors affecting outcome in a uniformly treated series of locally advanced rectal cancer (LARC) patients. Methods: Between 2004 and 2008, 107 patients with cT3 (threatening the mesorectal fascia or <5 cm from the anal verge), cT4 or cN2 rectal cancer were treated with preoperative CRT (25 × 2 Gy with capecitabine) and TME 6–8 weeks later. Central histopathological review followed. Tumour regression grade (TRG) was scored in pCR, near-pCR, response and no response. Cox regression was performed to identify prognosticators. Results: The 3-year distant metastasis-free interval, disease-free rate and overall survival rate were 82%, 73% and 87% (median 44 months follow-up). TRG consisted of 20% pCR, 11% near-pCR, 55% response and 14% no response. 6/21 pCR patients harboured nodal metastases. 5/12 near-pCR had ypT3 disease, while 6 harboured node metastases. 5/12 near-PCR patients developed distant metastases. ypN and TRG were powerful outcome discriminators. Conclusion: The high number of near-pCR with ypT3 or ypN1/2 and their poor outcome demonstrates that “watch-and-wait” in LARC patients should be applied with care

  6. Locally advanced breast implant associated anaplastic large cell lymphoma: A case report of successful treatment with radiation and chemotherapy

    Directory of Open Access Journals (Sweden)

    Christopher Fleighton Estes

    2015-02-01

    Full Text Available The development of breast implant associated anaplastic large cell lymphoma (ALCL is a rare phenomenon. A typical presentation is an effusion associated with a breast implant. Less commonly, disease can become more advanced locoregionally or distantly. The optimal treatment schema is a topic of debate: localized ALCL can potentially be cured with implant removal alone, while other cases in the literature, including those that are more advanced, have been treated with varying combinations of surgery, chemotherapy, and external beam radiotherapy. This is a case report of breast implant ALCL with pathologically proven lymph node involvement, the fifth such patient reported. Our patient experienced a favorable outcome with radiation therapy and chemotherapy.

  7. Efficacy and safety of palliative chemotherapy for patients with advanced breast cancer pretreated with anthracyclines and taxanes: a systematic review

    NARCIS (Netherlands)

    Oostendorp, L.J.M.; Stalmeier, P.F.M.; Donders, A.R.T.; Graaf, W.T.A. van der; Ottevanger, P.B.

    2011-01-01

    No standard monotherapy or combination palliative chemotherapy currently exists for patients with advanced breast cancer pretreated with anthracyclines and taxanes. In this systematic review we assess the current knowledge on the efficacy and safety of palliative single-agent chemotherapy drugs--cap

  8. Open comparative trial of formestane versus megestrol acetate in postmenopausal patients with advanced breast cancer previously treated with tamoxifen

    NARCIS (Netherlands)

    Freue, M; Kjaer, M; Boni, C; Joliver, J; Janicke, F; Willemse, PHB; Coombes, RC; Van Belle, S; Perez-Carrion, R; Zieschang, J; de Palacios, PI; Rose, C

    2000-01-01

    The aim of the trial was to compare efficacy and safety of the aromatase inhibitor formestane (250 mg i.m. given every 2 weeks) with the progestin megestrol acetate (160 mg administered orally once daily), as second-line therapy in postmenopausal patients with advanced breast cancer previously treat

  9. Influences of neoadjuvant chemotherapy for serum tumor markers, invasion and metastasis related indexes of patients with advanced breast cancer

    Institute of Scientific and Technical Information of China (English)

    Chuan-Xi Chen

    2016-01-01

    Objective:To explore and analyze the influences on neoadjuvant chemotherapy for serum tumor markers, invasion and metastasis related indexes of patients with advanced breast cancer.Methods:Patients with advanced breast cancer who had been treated in our hospital from February 2010 to February 2014 were randomly selected as research objects. They were randomly divided into control group (conventional surgical treatment group) and observation group (neoadjuant chemotherapy group). There were 32 cases of each group. Then, the changes of the different periods of serum tumor markers, invasion and metastasis related indexes in pretherapy and post-treatment of patients with advanced breast cancer in the two groups were observed.Results:The postoperative serum tumor markers, invasion and metastasis related indexes in different periods of the observation group were all lower than those of the control group, and the postoperative evaluation indexes of the two groups had significant difference. Conclusions:Neoadjuvant chemotherapy has great influences on serum tumor markers, invasion and metastasis related indexes of patients with advanced breast cancer and possesses high clinical application values.

  10. External and interstitial radiation therapy of locally advanced carcinoma of the breast

    International Nuclear Information System (INIS)

    The present report concerns 164 cases of locally advanced breast cancer (stage III), treated between December 1977 and January 1987. The local therapy consisted exclusively of radiation therapy including external beam irradiation (60 Co) up to 45-50 Gy supplemented with a boost, delivered either by interstitial 192Ir (30-40 Gy) or by external irradiation from limited fields (15-22 Gy). Eighty-one patients also received adjuvant systemic chemotherapy. A total of 51 local failures (31%) occurred. The actuarial rate of survival with local tumor control was 53% at 5 years and 49% at 6.5 years. A total of 69 patients developed distant metastases (42%). The actuarial survival without distant failure was 43% at 5 years and 37% at 6 years. The actuarial survival rate at 5 years was 53% and 38% at 7 years. The cosmetic results were excellent in 58 patients and poor in 13 patients (9.7%). The result suggests that stage III breast cancer can be satisfactorily treated with radiation therapy alone as local treatment. (orig.)

  11. Benefits of Medroxyprogesterone Acetate (MPA) in Advanced or Recurrent Breast Cancer with Higher Serum Concertration.

    Science.gov (United States)

    Nishimura; Nagao; Matsuda; Baba; Matsuoka; Yamashita; Fukuda; Higuchi; Saiki

    1995-10-31

    The efficacy of medroxyprogesterone acetate (MPA) therapy in controlling progressive measurable metastatic breast cancer was assessed in 61 patients. In addition serum MPA concentrations were measured by high performance liquid chromatography (HPLC) and subjective effects of treatment were monitored. Overall 24 patients (39.3%) achieved an objective response(2 complete responses [ CR ] and 22 partial responses [ PR ]). There was no significant relationships between response to therapy and menopausal status, metastatic sites, previous therapy, histological type, or disease-free interval. Patients with estrogen (ER) and progesterone (PgR) receptor-positive tumors responded more frequently. Significant differences in serum MPA concentrations were seen between responders and non-responders, objective tumor shrinkage being seen in patients with serum levels in excess of 55 ng/ml. There were few cases responding to the therapy with serum MPA concentrations lower than 25 ng/ml. The serum MPA levels significantly correlated with an improvement in the performance status and survival. Patients with serum MPA concentrations lower than 25 ng/ml had significantly poorer survival. There was a significant relationship between MPA level and dose per area of boby surface (mg/ m(2)) in cases with CR or PR or no change (NC). However, the serum levels of patients with progressive disease despite therapy were lower than the expected levels based on the body surface area. This study demonstrated that serum MPA concentration is a determining factor for therapeutic benefit in advanced or recurrent breast cancer. PMID:11091543

  12. Laser immunotherapy for treatment of patients with advanced breast cancer and melanoma

    Energy Technology Data Exchange (ETDEWEB)

    Li Xiaosong [Department of Oncology, the First Affiliated Hospital of Chinese PLA General Hospital, Beijing (China); Hode, Tomas; Guerra, Maria C [Immunophotonics Inc., 1601 South Providence Road, Columbia, Missouri 65211 (United States); Ferrel, Gabriela L [Hospital Nacional Edgardo Rebagliati Martins, Av. Edgardo Rebagliati 490 - Jesus Maria, Lima (Peru); Nordquist, Robert E [Wound Healing of Oklahoma, Inc., Oklahoma City, Oklahoma (United States); Chen, Wei R, E-mail: wchen@uco.edu [Department of Engineering and Physics, University of Central Oklahoma, Edmond, Oklahoma (United States)

    2011-02-01

    Laser immunotherapy (LIT) was developed for the treatment of metastatic tumors. It combines local selective photothermal interaction and active immunological stimulation to induce a long-term, systemic anti-tumor immunity. During the past sixteen years, LIT has been advanced from bench-top to bedside, with promising outcomes. In our pre-clinical and preliminary clinical studies, LIT has demonstrated the capability in inducing immunological responses, which not only can eradicate the treated primary tumors, but also can eliminate untreated metastases at distant sites. Specifically, LIT has been used to treat advanced melanoma and breast cancer patients during the past five years. LIT was shown to be effective in controlling both primary tumors and distant metastases in late-stage patients, who have failed conventional therapies such as surgery, chemotherapy, radiation, and other more advanced approaches. The methodology and the development of LIT are presented in this paper. The patients' responses to LIT are also reported in this paper. The preliminary results obtained in these studies indicated that LIT could be an effective modality for the treatment of patients with late-stage, metastatic cancers, who are facing severely limited options.

  13. Laser immunotherapy for treatment of patients with advanced breast cancer and melanoma

    International Nuclear Information System (INIS)

    Laser immunotherapy (LIT) was developed for the treatment of metastatic tumors. It combines local selective photothermal interaction and active immunological stimulation to induce a long-term, systemic anti-tumor immunity. During the past sixteen years, LIT has been advanced from bench-top to bedside, with promising outcomes. In our pre-clinical and preliminary clinical studies, LIT has demonstrated the capability in inducing immunological responses, which not only can eradicate the treated primary tumors, but also can eliminate untreated metastases at distant sites. Specifically, LIT has been used to treat advanced melanoma and breast cancer patients during the past five years. LIT was shown to be effective in controlling both primary tumors and distant metastases in late-stage patients, who have failed conventional therapies such as surgery, chemotherapy, radiation, and other more advanced approaches. The methodology and the development of LIT are presented in this paper. The patients' responses to LIT are also reported in this paper. The preliminary results obtained in these studies indicated that LIT could be an effective modality for the treatment of patients with late-stage, metastatic cancers, who are facing severely limited options.

  14. Revisiting the relationship between tumour volume and diameter in advanced NSCLC patients: An exercise to maximize the utility of each measure to assess response to therapy

    International Nuclear Information System (INIS)

    Aim: To revisit the presumed relationship between tumour diameter and volume in advanced non-small-cell lung cancer (NSCLC) patients, and determine whether the measured volume using volume-analysis software and its proportional changes during therapy matches with the calculated volume obtained from the presumed relationship and results in concordant response assessment. Materials and methods: Twenty-three patients with stage IIIB/IV NSCLC with a total of 53 measurable lung lesions, treated in a phase II trial of erlotinib, were studied with institutional review board approval. Tumour volume and diameter were measured at baseline and at the first follow-up computed tomography (CT) examination using volume-analysis software. Using the measured diameter (2r) and the equation, calculated volume was obtained as (4/3)πr3 at baseline and at the follow-up. Percent volume change was obtained by comparing to baseline for measured and calculated volumes, and response assessment was assigned. Results: The measured volume was significantly smaller than the calculated volume at baseline (median 11,488.9 mm3 versus 17,148.6 mm3; p < 0.0001), with a concordance correlation coefficient (CCC) of 0.7022. At follow-up, the measured volume was once again significantly smaller than the calculated volume (median 6573.5 mm3 versus 9198.1 mm3; p = 0.0022), with a CCC of 0.7408. Response assessment by calculated versus measured volume changes had only moderate agreement (weighted κ = 0.545), with discordant assessment results in 20% (8/40) of lesions. Conclusion: Calculated volume based on the presumed relationship significantly differed from the measured volume in advanced NSCLC patients, with only moderate concordance in response assessment, indicating the limitations of presumed relationship. - Highlights: • Response assessment by measured vs calculated values has only moderate agreement. • It is important to obtain the actual measured values for tumor response assessment

  15. A structured review of health utility measures and elicitation in advanced/metastatic breast cancer

    Directory of Open Access Journals (Sweden)

    Hao Y

    2016-06-01

    Full Text Available Yanni Hao,1 Verena Wolfram,2 Jennifer Cook2 1Novartis Pharmaceuticals, East Hanover, NJ, USA; 2Adelphi Values, Bollington, UK Background: Health utilities are increasingly incorporated in health economic evaluations. Different elicitation methods, direct and indirect, have been established in the past. This study examined the evidence on health utility elicitation previously reported in advanced/metastatic breast cancer and aimed to link these results to requirements of reimbursement bodies. Methods: Searches were conducted using a detailed search strategy across several electronic databases (MEDLINE, EMBASE, Cochrane Library, and EconLit databases, online sources (Cost-effectiveness Analysis Registry and the Health Economics Research Center, and web sites of health technology assessment (HTA bodies. Publications were selected based on the search strategy and the overall study objectives. Results: A total of 768 publications were identified in the searches, and 26 publications, comprising 18 journal articles and eight submissions to HTA bodies, were included in the evidence review. Most journal articles derived utilities from the European Quality of Life Five-Dimensions questionnaire (EQ-5D. Other utility measures, such as the direct methods standard gamble (SG, time trade-off (TTO, and visual analog scale (VAS, were less frequently used. Several studies described mapping algorithms to generate utilities from disease-specific health-related quality of life (HRQOL instruments such as European Organization for Research and Treatment of Cancer Quality of Life Questionnaire – Core 30 (EORTC QLQ-C30, European Organization for Research and Treatment of Cancer Quality of Life Questionnaire – Breast Cancer 23 (EORTC QLQ-BR23, Functional Assessment of Cancer Therapy – General questionnaire (FACT-G, and Utility-Based Questionnaire-Cancer (UBQ-C; most used EQ-5D as the reference. Sociodemographic factors that affect health utilities, such as age, sex

  16. Breast

    International Nuclear Information System (INIS)

    Ultrasound is not an efficacious screening modality to detect early-stage breast malignancy in a clinically unremarkable population of women. Computed body tomography is similarly not practical for screening because of slice thickness and partial volume averaging, a higher radiation dose than modern mammography, and the lack of availability of such units for such a high throughput requirement. Nevertheless, these two imaging modalities can be very useful in management to guide the least invasive and efficacious treatment of the patient. X-ray mammography remains the principal imaging modality in the search for breast malignancy, but ultrasound is the single most important second study in the diagnostic evaluation of the breast. The combined use of these techniques and the ability to perform guided aspiration and localization procedures can result in a reduction in the surgical removal of benign cysts and reduction in the amount of tissue volume required if excision becomes necessary

  17. 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

    by cells in the tumour microenvironment of most if not all these lesions. To this end, we applied a phased biomarker discovery research strategy to the analysis of these samples rather than comparing all samples among each other, with inherent inter and intra-sample variability problems. To this end...

  18. 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

    by cells in the tumour microenvironment of most if not all these lesions. To this end, we applied a phased biomarker discovery research strategy to the analysis of these samples rather than comparing all samples among each other, with inherent inter and intra-sample variability problems. To this end...

  19. DNA damage response mediators MDC1 and 53BP1: constitutive activation and aberrant loss in breast and lung cancer, but not in testicular germ cell tumours

    Czech Academy of Sciences Publication Activity Database

    Bartkova, J.; Hořejší, Zuzana; Sehested, M.; Nesland, J.M.; Rajpert-De Meyts, E.; Skakkebaek, N.E.; Stucki, M.; Jackson, S.; Lukas, J.; Bartek, Jiří

    2007-01-01

    Roč. 26, č. 53 (2007), s. 7414-7422. ISSN 0950-9232 Institutional research plan: CEZ:AV0Z50520514 Keywords : DNA damage response * cancer * MDC1 and 53BP1 defects * tumour suppressors Subject RIV: EB - Genetics ; Molecular Biology Impact factor: 6.440, year: 2007

  20. Targeting hypoxic tumour cells to overcome metastasis

    International Nuclear Information System (INIS)

    The microenvironment within solid tumours can influence the metastatic dissemination of tumour cells, and recent evidence suggests that poorly oxygenated (hypoxic) cells in primary tumours can also affect the survival and proliferation of metastatic tumour cells in distant organs. Hypoxic tumour cells have been historically targeted during radiation therapy in attempts to improve loco-regional control rates of primary tumours since hypoxic cells are known to be resistant to ionizing radiation-induced DNA damage. There are, therefore, a number of therapeutic strategies to directly target hypoxic cells in primary (and metastatic) tumours, and several compounds are becoming available to functionally inhibit hypoxia-induced proteins that are known to promote metastasis. This mini-review summarizes several established and emerging experimental strategies to target hypoxic cells in primary tumours with potential clinical application to the treatment of patients with tumour metastases or patients at high risk of developing metastatic disease. Targeting hypoxic tumour cells to reduce metastatic disease represents an important advance in the way scientists and clinicians view the influence of tumour hypoxia on therapeutic outcome

  1. The correlation between cell-free DNA and tumour burden was estimated by PET/CT in patients with advanced NSCLC

    DEFF Research Database (Denmark)

    Nygaard, A D; Holdgaard, Paw; Spindler, K-L G;

    2014-01-01

    -FDG) PET/computed tomography (CT) scan was performed and evaluated in terms of metabolic tumour volume (MTV) and total lesion glycolysis (TLG). Tumour contours were delineated semi-automatically by a threshold standardised uptake value (SUV) of 2.5. The primary end point was correlation among cfDNA, MTV...

  2. Estimation of BCL-2 protein in carcinoma of the breast and its clinical correlation in locally advanced breast cancer

    Directory of Open Access Journals (Sweden)

    Aggarwal Himanshu

    2007-01-01

    Full Text Available The change in expression of apoptotic markers (Bcl-2 and Bax proteins brought about by various chemotherapeutic regimens is being used for its predictive value for assessing response to neoadjuvant chemotherapy (NACT in locally advanced breast carcinoma (LABC. Aims: (1 Estimation of Bcl 2 expression in LABC, (2 Any change in Bcl 2 expression following chemotherapy in LABC, (3 Any relation of Bcl 2 estimation to changes in size of tumor, nodal status, age, and menopausal status. Settings and Design: This was a prospective study of 120 cases of LABC. Materials and Methods: All cases were subjected to biopsy and the tissue was evaluated immunohistochemically for apoptotic marker Bcl-2 family protein. Three cycles of NACT were given at three-weekly intervals. Modified radical mastectomy was performed and the specimens were re-evaluated for any change in the Bcl-2 family protein. The clinical response and immunohistochemical response were correlated and compared. Statistical Analysis: Coefficient of correlation was calculated by Pearson correlation coefficient (P-value. Results: Clinical response, as measured by reduction in the tumor size, was observed in 81 (67.5% patients while immunohistochemical response was observed in 67 (55.8% patients. Correlation between immunohistochemical and clinical response was found to be statistically significant (P = 0.02. Nodal response was seen in 72 (60% patients. There were no patients in the N o group; 22 (53.7% of the N 1 patients were down-staged to N o , while 19 (46.3% remained N 1 . In patients with N 2 disease, 11 (13.9% were down-staged to N o status, 39 (49.4% were down-staged to N 1 status, and 29 (36.7% did not show any response. Immunohistochemical response was observed in 67 (55.8% patients. Correlation between immunohistochemical and nodal responses was also found to be statistically significant (P = 0.03. Conclusions: This significant positive correlation between clinical and immunohistochemical

  3. Histological type and marker expression of the primary tumour compared with its local recurrence after breast-conserving therapy for ductal carcinoma in situ

    OpenAIRE

    Bijker, N; Peterse, J L; Duchateau, L.; Robanus-Maandag, E. C.; Bosch, C A J; Duval, C.; Pilotti, S.; Vijver, M J van de

    2001-01-01

    We have investigated primary ductal carcinomas in situ (DCIS) of the breast and their local recurrences after breast-conserving therapy (BCT) for histological characteristics and marker expression. Patients who were randomized in the EORTC trial 10853 (wide local excision versus excision plus radiotherapy) and who developed a local recurrence were identified. Histology was reviewed for 116 cases; oestrogen and progesterone receptor status, and HER2/ neu and p53 overexpression were assessed fo...

  4. THORACO - ABDOMINAL FLAP FOR RESURFACING LARGE POST MASTECTOMY DEFECTS IN LOCALLY ADVANCED CA. BREAST

    Directory of Open Access Journals (Sweden)

    Srinivasa Rao

    2015-02-01

    Full Text Available Covering of large wounds after mastectomy in locally advanced Ca breast with skin that can withstand radiotherapy is a challenge to the surgeon. Here this study we used a local advancement flap from the adjacent area called Thoraco - A bdominal F la p (TA flap for such giant defects. This is based on superficial and lumbar arteries and is thick to with stand consequent RT . MATERIALS AND METHODS: Of the total 107 cases of LABC 32 had post mastectomy defects of larger than 12 cm and could not be closed by simple approximation. Among the 32 cases 17 cases are covered by split thickness skin grafting. 15 cases are covered by TA flap. These cases are assessed for mean operating time, mean blood loss, post - operative stay, flap necrosis and viability of the f lap after radiotherapy. RESULTS: There is minimal extra time or blood loss in these cases . All the flaps healed well except for small edge necrosis in 4 cases. In all the patients we could start radiotherapy in the fourth week of surgery and all the flaps withstood RT well. After further evaluation probably this can be recommended as procedure for giant post mastectomy defects particularly for those who require RT early

  5. Oral vinorelbine: its role in advanced breast cancer pre-treated with anthracycline and taxane chemotherapies

    Directory of Open Access Journals (Sweden)

    Fausto Petrelli

    2011-12-01

    Full Text Available Metastatic breast cancer (BC remains an incurable disease and clinical benefit and prolongation of time to progression are the main end-points in advanced setting. A safe and feasible schedule of administration is the principal option in pre-treated and symptomatic patients, as in the elderly too. Oral vinorelbine represents a good choice for its toxicity profile and activity in anthracycline and taxane-pre-treated BC patients. A 20–30% response rate (RR can be obtained when used as single agent. In phase II trials, involving fit patients, and when oral vinorelbine is used in combination with other agents (e.g., capecitabine a RR of 50-60% has been observed. In HER2-positive BC a combination of oral vinorelbine and trastuzumab has a dramatic activity in first-line therapy and is a reasonable choice in trastuzumab pre-treated patients. In conclusion, oral vinorelbine represents a pivotal choice in advanced and pre-treated BC both as single agent and in combination with others.

  6. The combination of FDG PET and dynamic contrast-enhanced MRI improves the prediction of disease-free survival in patients with advanced breast cancer after the first cycle of neoadjuvant chemotherapy

    International Nuclear Information System (INIS)

    The aim of this study was to investigate the potential of FDG PET/CT and MRI in predicting disease-free survival (DFS) after neoadjuvant chemotherapy (NAC) and surgery in patients with advanced breast cancer. The analysis included 54 women with advanced breast cancer. All patients received three cycles of NAC, underwent curative surgery, and then received three cycles of additional chemotherapy. Before and after the first cycle of NAC, all patients underwent sequential PET/CT and MRI. All patients were analysed using a diverse range of parameters. including maximal standardized uptake value (SUV), percent change in SUV (ΔSUV), initial slope of the enhancement curve (MRslope), apparent diffusion coefficient (ADC), tumour size, change in MRslope (ΔMRslope), change in ADC (ΔADC), change in tumour size (Δsize) and other clinicopathological parameters. The relationships between covariates and DFS after surgery were analysed using the Kaplan-Meier method and the multivariate Cox proportional hazards model. Time-dependent receiver operating characteristic curves were used to determine the optimal cut-off values of imaging parameters for DFS. Of the 54 patients, 13 (24 %) experienced recurrence at a median follow-up of 38 months (range 25 - 45 months). Univariate and multivariate analyses showed that a lesser decline in SUV, a lesser decline in MRslope, a lesser increase in ADC, and ER negativity were significantly associated with a poorer DFS (P = 0.0006, ΔSUV threshold -41 %; P = 0.0016, ΔMRslope threshold -6 %; P = 0.011, ΔADC threshold 11 %; and P = 0.0086, ER status, respectively). Patients with a combination of ΔSUV >-41 % and ΔMRslope >-6 % showed a significantly higher recurrence rate (77.8 %) than the remaining of patients (13.3 %, P < 0.0001). Functional parameters of both FDG PET and MRI after the first cycle of NAC are useful for predicting DFS in patients with advanced breast cancer. This approach could lead to an improvement in patient care because

  7. The combination of FDG PET and dynamic contrast-enhanced MRI improves the prediction of disease-free survival in patients with advanced breast cancer after the first cycle of neoadjuvant chemotherapy

    Energy Technology Data Exchange (ETDEWEB)

    Lim, Ilhan; Kim, Byung II; Choi, Chang Woon; Lim, Sang Moo [Korea Institute of Radiological and Medical Sciences (KIRAMS), Department of Nuclear Medicine, Korea Cancer Center Hospital, 75 Nowongil, Nowon Gu, Seoul (Korea, Republic of); Korea Institute of Radiological and Medical Sciences (KIRAMS), Molecular Imaging Research Center, Seoul (Korea, Republic of); Noh, Woo Chul; Kim, Hyun-Ah; Kim, Eun-Kyu [Korea Institute of Radiological and Medical Sciences (KIRAMS), Department of Surgery, Korea Cancer Center Hospital, Seoul (Korea, Republic of); Park, Jihyun; Byun, Byung Hyun [Korea Institute of Radiological and Medical Sciences (KIRAMS), Department of Nuclear Medicine, Korea Cancer Center Hospital, 75 Nowongil, Nowon Gu, Seoul (Korea, Republic of); Park, Ji Ae; Kim, Kyeong Min [Korea Institute of Radiological and Medical Sciences (KIRAMS), Molecular Imaging Research Center, Seoul (Korea, Republic of); Park, Ko Woon [Korea Institute of Radiological and Medical Sciences (KIRAMS), Department of Radiology, Korea Cancer Center Hospital, Seoul (Korea, Republic of); Lee, Seung Sook [Korea Institute of Radiological and Medical Sciences (KIRAMS), Department of Pathology, Korea Cancer Center Hospital, Seoul (Korea, Republic of); You, Eun Young [Gachon University School of Medicine and Science, Department of Radiology, Gil Hospital, Incheon (Korea, Republic of)

    2014-10-15

    The aim of this study was to investigate the potential of FDG PET/CT and MRI in predicting disease-free survival (DFS) after neoadjuvant chemotherapy (NAC) and surgery in patients with advanced breast cancer. The analysis included 54 women with advanced breast cancer. All patients received three cycles of NAC, underwent curative surgery, and then received three cycles of additional chemotherapy. Before and after the first cycle of NAC, all patients underwent sequential PET/CT and MRI. All patients were analysed using a diverse range of parameters. including maximal standardized uptake value (SUV), percent change in SUV (ΔSUV), initial slope of the enhancement curve (MRslope), apparent diffusion coefficient (ADC), tumour size, change in MRslope (ΔMRslope), change in ADC (ΔADC), change in tumour size (Δsize) and other clinicopathological parameters. The relationships between covariates and DFS after surgery were analysed using the Kaplan-Meier method and the multivariate Cox proportional hazards model. Time-dependent receiver operating characteristic curves were used to determine the optimal cut-off values of imaging parameters for DFS. Of the 54 patients, 13 (24 %) experienced recurrence at a median follow-up of 38 months (range 25 - 45 months). Univariate and multivariate analyses showed that a lesser decline in SUV, a lesser decline in MRslope, a lesser increase in ADC, and ER negativity were significantly associated with a poorer DFS (P = 0.0006, ΔSUV threshold -41 %; P = 0.0016, ΔMRslope threshold -6 %; P = 0.011, ΔADC threshold 11 %; and P = 0.0086, ER status, respectively). Patients with a combination of ΔSUV >-41 % and ΔMRslope >-6 % showed a significantly higher recurrence rate (77.8 %) than the remaining of patients (13.3 %, P < 0.0001). Functional parameters of both FDG PET and MRI after the first cycle of NAC are useful for predicting DFS in patients with advanced breast cancer. This approach could lead to an improvement in patient care because

  8. DEGRO practical guidelines for radiotherapy of breast cancer V. Therapy for locally advanced and inflammatory breast cancer, as well as local therapy in cases with synchronous distant metastases

    Energy Technology Data Exchange (ETDEWEB)

    Budach, Wilfried; Matuschek, Christiane; Boelke, Edwin [University Hospital, Heinrich-Heine-University Duesseldorf, Klinik fuer Strahlentherapie und Radioonkologie, Duesseldorf (Germany); Dunst, Juergen [University Hospital Schleswig-Holstein, Luebeck (Germany); Feyer, Petra [Vivantes Hospital Neukoelln, Berlin (Germany); Fietkau, Rainer; Sauer, Rolf [University Hospital Erlangen, Erlangen (Germany); Harms, Wolfgang [St. Clara Hospital, Basel (Switzerland); Piroth, Marc D. [Helios Hospital, Wuppertal (Germany); Sautter-Bihl, Marie-Luise [Municipal Hospital, Karlsruhe (Germany); Sedlmayer, Felix [Paracelsus Medical University Hospital, Salzburg (Austria); Wenz, Frederick [Universitaetsmedizin Mannheim, Mannheim (Germany); Haase, Wulf; Souchon, Rainer; Collaboration: Breast Cancer Expert Panel of the German Society of Radiation Oncology (DEGRO)

    2015-08-15

    The purpose of this work is to give practical guidelines for radiotherapy of locally advanced, inflammatory and metastatic breast cancer at first presentation. A comprehensive survey of the literature using the search phrases ''locally advanced breast cancer'', ''inflammatory breast cancer'', ''breast cancer and synchronous metastases'', ''de novo stage IV and breast cancer'', and ''metastatic breast cancer'' and ''at first presentation'' restricted to ''clinical trials'', ''randomized trials'', ''meta-analysis'', ''systematic review'', and ''guideline'' was performed and supplemented by using references of the respective publications. Based on the German interdisciplinary S3 guidelines, updated in 2012, this publication addresses indications, sequence to other therapies, target volumes, dose, and fractionation of radiotherapy. International and national guidelines are in agreement that locally advanced, at least if regarded primarily unresectable and inflammatory breast cancer should receive neoadjuvant systemic therapy first, followed by surgery and radiotherapy. If surgery is not amenable after systemic therapy, radiotherapy is the treatment of choice followed by surgery, if possible. Surgery and radiotherapy should be administered independent of response to neoadjuvant systemic treatment. In patients with a de novo diagnosis of breast cancer with synchronous distant metastases, surgery and radiotherapy result in considerably better locoregional tumor control. An improvement in survival has not been consistently proven, but may exist in subgroups of patients. Radiotherapy is an important part in the treatment of locally advanced and inflammatory breast cancer that should be given to all patients regardless to the intensity and effect of

  9. Efficacy of neoadjuvant chemotherapy in down staging locally advanced pre-menopausal breast cancer in Eastern Nigeria: Is four courses adequate?

    OpenAIRE

    Ochonma Amobi Egwuonwu; Stanley Nnamdi Anyanwu; Alexander Maduaburochukwu Nwofor

    2013-01-01

    Context: Breast cancer is the most frequent cancer among women in most part of the world and in Nigeria. Neoadjuvant chemotherapy (NAC) has been demonstrated to be a helpful strategy in the context of locally advanced breast cancer (LABC). Aims: To determine if the use of four courses of doxorubicin based neoadjuvant chemotherapeutic regimen will result in significant primary tumor down-staging. Settings and Design: One year prospective study of premenopausal breast cancer patients pres...

  10. Combined radiotherapy with cis- or carboplatin in advanced head and neck tumours. Kombinierte Radiotherapie mit Cis- oder Carboplatin bei fortgeschrittenen Kopf-Hals-Tumoren

    Energy Technology Data Exchange (ETDEWEB)

    Zamboglou, N.; Pape, H.; Schnabel, T.; Wurm, R.; Bannach, B.; Fuerst, G.; Schmitt, G. (Duesseldorf Univ. (Germany, F.R.). Klinik fuer Strahlentherapie und Radiologische Onkologie)

    1989-09-01

    This report reviews the treatment results of 111 patients with stage T3-4, N0-3, M0, biopsy proven squamous cell carcinoma of the oropharynx and oral cavity. All patients were treated by primary irradiation with 1.8 to 2 Gy per day for five days a week up to a target volume dose of 39,6 or 40 Gy. Simultaneously 20 mg/m{sup 2} cisplatin was given under hyperhydration and mannitol diuresis on days 1 to 5. In case of partial tumour regression radiotherapy was continued up to 70 Gy with another course of cisplatin. In case of minor response surgery was interposed followed by subsequent irradiation with 30 Gy and a second course of cisplatin. 67% of the patients showed an initial complete tumour involution and 27% a partial response. The five year actuarial survival rate with a minimum follow-up of two years is 47,6%. More than 96% of the long term survivors showed a complete response after the end of treatment. Carboplatin (CBDCA) is a second generation platinum analogon and has shown comparable antitumour activity but less nephro- and neurotoxicity than cisplatin in head and neck cancer. In order to determine the feasibility and efficacy of simultaneous application of CBDCA and radiotherapy a phase I-II study is going on. Patients with advanced squamous carcinoma of the head and neck were separated into three groups which received 60 mg/m{sup 2}, 70 mg/m{sup 2} and 80 mg/m{sup 2} CBDCA from days 1 to 5 and 28 to 32. Radiotherapy was administrated up to a target absorbed dose of 70 Gy, 5x2 Gy/week in shrinking field technique. The group which received 80 mg/m{sup 2} CBDCA reached the myelotoxicity limit so that subsequent patients were treated with 70 mg/m{sup 2}. Among 30 patients who completed the treatment, 22 showed a complete (CR) and eight a partial remission (PR). (orig./MG).

  11. Recent Advances in the Use of Metformin: Can Treating Diabetes Prevent Breast Cancer?

    OpenAIRE

    Hatoum, Diana; Eileen M. McGowan

    2015-01-01

    There is substantial epidemiological evidence pointing to an increased incidence of breast cancer and morbidity in obese, prediabetic, and diabetic patients. In vitro studies strongly support metformin, a diabetic medication, in breast cancer therapy. Although metformin has been heralded as an exciting new breast cancer treatment, the principal consideration is whether metformin can be used as a generic treatment for all breast cancer types. Importantly, will metformin be useful as an inexpen...

  12. Antenatally detected solid tumour of kidney

    OpenAIRE

    Panda, Shasanka Shekhar; Mandelia, Ankur; Gupta, Devendra Kumar; Singh, Amit

    2014-01-01

    Congenital renal tumours are rare and usually benign. Polyhydramnios is the most common mode of presentation. Although most cases have been diagnosed postnatally, with advances in imaging technology, an increasing number of cases are being detected on antenatal scans. We describe a case of solid tumour of kidney detected in the second trimester of pregnancy and managed by surgery in the postnatal period.

  13. Sequencing chemotherapy and radiotherapy in locoregional advanced breast cancer patients after mastectomy – a retrospective analysis

    International Nuclear Information System (INIS)

    Combined chemo- and radiotherapy are established in breast cancer treatment. Chemotherapy is recommended prior to radiotherapy but decisive data on the optimal sequence are rare. This retrospective analysis aimed to assess the role of sequencing in patients after mastectomy because of advanced locoregional disease. A total of 212 eligible patients had a stage III breast cancer and had adjuvant chemotherapy and radiotherapy after mastectomy and axillary dissection between 1996 and 2004. According to concerted multi-modality treatment strategies 86 patients were treated sequentially (chemotherapy followed by radiotherapy) (SEQgroup), 70 patients had a sandwich treatment (SW-group) and 56 patients had simultaneous chemoradiation (SIM-group) during that time period. Radiotherapy comprised the thoracic wall and/or regional lymph nodes. The total dose was 45–50.4 Gray. As simultaneous chemoradiation CMF was given in 95.4% of patients while in sequential or sandwich application in 86% and 87.1% of patients an anthracycline-based chemotherapy was given. Concerning the parameters nodal involvement, lymphovascular invasion, extracapsular spread and extension of the irradiated region the three treatment groups were significantly imbalanced. The other parameters, e.g. age, pathological tumor stage, grading and receptor status were homogeneously distributed. Looking on those two groups with an equally effective chemotherapy (EC, FEC), the SEQ- and SW-group, the sole imbalance was the extension of LVI (57.1 vs. 25.6%, p < 0.0001). 5-year overall- and disease free survival were 53.2%/56%, 38.1%/32% and 64.2%/50%, for the sequential, sandwich and simultaneous regime, respectively, which differed significantly in the univariate analysis (p = 0.04 and p = 0.03, log-rank test). Also the 5-year locoregional or distant recurrence free survival showed no significant differences according to the sequence of chemo- and radiotherapy. In the multivariate analyses the sequence had no

  14. Disparities in the Use of Radiation Therapy in Patients With Local-Regionally Advanced Breast Cancer

    International Nuclear Information System (INIS)

    Background: Radiation therapy (RT) is indicated for the treatment of local-regionally advanced breast cancer (BCa). Hypothesis: We hypothesized that black and Hispanic patients with local-regionally advanced BCa would receive lower rates of RT than their white counterparts. Methods: The Surveillance Epidemiology and End Results database was used to identify white, black, Hispanic, and Asian patients with invasive BCa and ≥10 metastatic lymph nodes diagnosed between 1988 and 2005. Univariate and multivariate logistic regression evaluated the relationship of race/ethnicity with use of RT. Multivariate models stratified for those undergoing mastectomy or lumpectomy. Results: Entry criteria were met by 12,653 patients. Approximately half of the patients did not receive RT. Most patients were white (72%); the remainder were Hispanic (10.4%), black (10.3%), and Asian (7.3%). On univariate analysis, Hispanics (odd ratio [OR] 0.89; 95% confidence interval [CI], 0.79-1.00) and blacks (OR 0.79; 95% CI, 0.70-0.89) were less likely to receive RT than whites. On multivariate analysis, blacks (OR 0.76; 95% CI, 0.67-0.86) and Hispanics (OR 0.80; 95% CI, 0.70-0.90) were less likely than whites to receive RT. Disparities persisted for blacks (OR 0.74; 95% CI, 0.64-0.85) and Hispanics (OR 0.77; 95% CI, 0.67-0.89) who received mastectomy, but not for those who received lumpectomy. Conclusions: Many patients with local-regionally advanced BCa do not receive RT. Blacks and Hispanics were less likely than whites to receive RT. This disparity was noted predominately in patients who received mastectomy. Future efforts at improving rates of RT are warranted. Efforts at eliminating racial/ethnic disparities should focus on black and Hispanic candidates for postmastectomy RT.

  15. Tumour targeting with systemically administered bacteria.

    LENUS (Irish Health Repository)

    Morrissey, David

    2012-01-31

    Challenges for oncology practitioners and researchers include specific treatment and detection of tumours. The ideal anti-cancer therapy would selectively eradicate tumour cells, whilst minimising side effects to normal tissue. Bacteria have emerged as biological gene vectors with natural tumour specificity, capable of homing to tumours and replicating locally to high levels when systemically administered. This property enables targeting of both the primary tumour and secondary metastases. In the case of invasive pathogenic species, this targeting strategy can be used to deliver genes intracellularly for tumour cell expression, while non-invasive species transformed with plasmids suitable for bacterial expression of heterologous genes can secrete therapeutic proteins locally within the tumour environment (cell therapy approach). Many bacterial genera have been demonstrated to localise to and replicate to high levels within tumour tissue when intravenously (IV) administered in rodent models and reporter gene tagging of bacteria has permitted real-time visualisation of this phenomenon. Live imaging of tumour colonising bacteria also presents diagnostic potential for this approach. The nature of tumour selective bacterial colonisation appears to be tumour origin- and bacterial species- independent. While originally a correlation was drawn between anaerobic bacterial colonisation and the hypoxic nature of solid tumours, it is recently becoming apparent that other elements of the unique microenvironment within solid tumours, including aberrant neovasculature and local immune suppression, may be responsible. Here, we consider the pre-clinical data supporting the use of bacteria as a tumour-targeting tool, recent advances in the area, and future work required to develop it into a beneficial clinical tool.

  16. Advances in Translational Medicine of Breast Cancer:From Bench to Bedside

    Institute of Scientific and Technical Information of China (English)

    HUANG Xin-en

    2015-01-01

    Breast cancer is one of the most common malignant tumors in women, and its incidence increases year by year. With the rapid development of human genomics, proteomics and bioinformatics, the basic and clinical results of breast cancer have emerged in endlessly. Translational medicine is a hot ifeld of international medicine, biological interdisciplinary science and many research funding projects at present, committed to establishing an academic exchange platform for global scientiifc researchers. In this study, the translational medicine of breast cancer was summarized and reviewed from the following aspects, including molecular markers related to breast cancer, molecular typing, individualized and molecular targeted therapies, relationship between molecular biology and imagiology of breast cancer.

  17. Association of carcinoma breast: grade and estrogen progesterone receptor expression

    International Nuclear Information System (INIS)

    To determine the association between histological grade of tumour and estrogen progesterone receptors (ER/PR) expression in unselected invasive carcinoma of breast in Malaysian patients. Study Design: An observational study. Place and Duration of Study: Advanced Medical and Dental Institute and Hospital, Kepala Batas, from year 2002 to 2007. Methodology: Ethical approval from Ministry of Health of Malaysia was obtained. Retrospective case records of patients presented between 2002- 2007 were reviewed for obtaining information on grade of tumour and expression of ER/PR in unselected carcinoma of breast patients. Records with missing data were discarded. Results: Out of 195 cases evaluated, 42 cases of grade-I tumour were recorded of which 08 (19%) tested positive for ER and 34 (81%) tested negative, 86 cases represented grade-II tumour of which 33 (38%) tested positive for ER and 53 (62%) were negative for ER, while out of 67 grade-III tumours 22 (33%) were positive for ER receptors while 45 (67%) were negative, (x/sup 2/ statistic (df) 4.831, p=0.089). For PR, 192 cases were evaluated and data was missing for 3 cases on PR status. Grade-I tumour consisted of 39 cases of which PR +ve represented 07 (17.94%) and 32 (82.05) cases PR -ve; 86 cases were of grade-II of which 31 (36.04%) were PR +ve and 55 (63.95%) PR -ve. Sixty seven cases of grade-III tumour of which 19 (28.35%) were PR +ve and 48 (71.64) were PR -ve (X/sup 2/ statistic (df): 4.297; p=0.117). Conclusion: ER/PR positivity trend was highest for grade-II tumours compared to grade-I and grade-III tumours. In general ER positivity was more with grade-II and grade-III tumours compared to grade I tumours. Although results did not reach statistical significance but there was a trend towards ER/PR positivity in grade-II and III tumours. So far, studies from South East Asia reported ER/PR expression more with low grade tumours. (author)

  18. The role of bisphosphonates in early- and advanced-stage breast cancer: have we finally optimized care?

    Science.gov (United States)

    Blanchette, Phillip S; Pritchard, Kathleen I

    2015-01-01

    Bisphosphonates have played an important role in the treatment of breast cancer, mainly in patients with bone metastasis, by reducing the risk of fracture, spinal cord compression, and hypercalcemia. Both oral and intravenous products are available and have strong supporting clinical evidence. Zoledronic acid, the most frequently used intravenous agent, has traditionally been given on a monthly dosing schedule. A novel every-12-weeks maintenance dosing schedule shows clinical equivalence and promises to improve safety, affordability, and quality of care. The Early Breast Cancer Trialists' Collaborative Group has recently helped clarify the controversial benefit of bisphosphonates in the adjuvant setting. Based on their meta-analysis, we now have strong evidence supporting the use of adjuvant bisphosphonates to help prevent the development of bone metastasis in postmenopausal breast cancer patients, which leads to a significant improvement in breast cancer-specific survival. We eagerly await the full publication of this practice-changing study, which continues the incremental advance of the treatment of patients with breast cancer. PMID:25595283

  19. Prediction of sensitivity to anticancer agents for patients with advanced or recurrent breast cancer by Tc-99m sestamibi

    International Nuclear Information System (INIS)

    Tc-99m Sestamibi (99mTc-MIBI) is known to be a substrate of P-glycoprotein (P-gp) that effluxes the drugs out of cancer cells. The overexpression of P-gp involved in multidrug resistance phenomenon in patients with advanced or recurrent breast cancers was shown in the plasma membrane of breast cancer cells. In this study, we examined the usefulness of 99mTc-MIBI scintigraphy for the prediction of sensitivity to anticancer agents in 8 cases with advanced or recurrent breast cancer. The retrospective analysis showed that the sensitivity to the chemotherapy could be evaluated in 3 cases by 99mTc-MIBI scintigraphy, but in the other 5 cases 99mTc-MIBI scintigraphy was not eligible for the prediction of sensitivity. Two out of 3 cases showed over 50% in reduction rate of target tumors (PR) with higher accumulation of 99mTc-MIBI, while another case with PD showed lower. These results suggest that the accumulation of 99mTc-MIBI could be associated with the sensitivity to P-gp-related anticancer agents, and that the functional analysis of P-gp by 99mTc-MIBI might be useful for the prediction of responsiveness of chemotherapy in patients with breast cancer. (author)

  20. Tumour markers in gynaecological practice

    International Nuclear Information System (INIS)

    Gynaecological cancers are fairly common in developing countries and represent about 26 % f all cancers. Application of cervical cytology screening nationally has made cervical cancer one of the most preventable malignant diseases thus eliminating the challenges of advanced cancer management. Tumour markers has played a most crucial role in this respect

  1. Locally Advanced Breast Implant-Associated Anaplastic Large-Cell Lymphoma: A Case Report of Successful Treatment with Radiation and Chemotherapy

    OpenAIRE

    Estes, Christopher F.; Zhang, Da; Reyes, Ruben; Korentager, Richard; McGinness, Marilee; Lominska, Christopher

    2015-01-01

    The development of breast implant-associated anaplastic large-cell lymphoma (ALCL) is a rare phenomenon. A typical presentation is an effusion associated with a breast implant. Less commonly, disease can be more advanced locoregionally or distantly. The optimal treatment schema is a topic of debate: localized ALCL can potentially be cured with implant removal alone, while other cases in the literature, including those that are more advanced, have been treated with varying combinations of surg...

  2. Self-reported health-related quality of life is an independent predictor of chemotherapy treatment benefit and toxicity in women with advanced breast cancer

    OpenAIRE

    Lee, C. K.; Stockler, M R; Coates, A. S.; Gebski, V.; Lord, S J; Simes, R J

    2010-01-01

    Background: Baseline health-related quality of life (QL) is associated with survival in advanced breast cancer. We sought to identify patients who were less likely to respond to chemotherapy and at greater risk of toxicity on the basis of their QL. Methods: We used data from three advanced breast cancer trials in which patients (n=378) were treated with cyclophosphamide, methotrexate and 5-fluouracil. Patients self-rated their QL using LASA scales for physical well-being (PWB), mood, pain, na...

  3. Summated chemotherapy dose-intensity versus loco-regional response in locally advanced breast cancer: Its possible implications

    OpenAIRE

    Datta N; Rajkumar A; Basu R

    2003-01-01

    BACKGROUND : Summated dose-intensity (SDI) of chemotherapy regimen could influence the outcome in malignancies. AIMS : To evaluate the implication of SDI and identify key drugs for loco-regional response in locally advanced breast cancer (LABC). Settings and design: This retrospective study was based on audit of records of LABC patients who had received neoadjuvant chemotherapy (NACT). MATERIAL AND METHODS : Actual unit dose-intensity (UDI) of each drug and corresponding SDI of every doxorubi...

  4. Efficacy of intraarterial chemoinfusion therapy for locally advanced breast cancer patients: a retrospective analysis of 28 cases

    Directory of Open Access Journals (Sweden)

    Zhang W

    2013-06-01

    Full Text Available Wei Zhang,1,* Rong Liu,1,* Yingying Wang,1 Sheng Qian,1 Jianhua Wang,1 Zhiping Yan,1 Hongwei Zhang21Department of Interventional Radiology, Zhongshan Hospital, Fudan University, Shanghai, People's Republic of China; 2Department of General Surgery, Zhongshan Hospital, Fudan University, Shanghai, People's Republic of China*These authors contributed equally to this workObjective: The objective of this study was to evaluate the outcome of image-guided delivery of intraarterially infused chemotherapeutic drugs for patients with locally advanced breast cancer.Methods: Twenty-eight patients with pathologically proven, locally advanced breast cancer received intraarterial chemoinfusion therapy (chemoinfusion with docetaxel 75 mg/m2 and epirubicin 50 mg/m2. Digital subtraction angiography was performed to determine tumor arterial blood supply and to guide chemotherapy infusion. Patients were evaluated for complete remission (CR and partial remission (PR.Results: Twenty-eight patients received a total of 64 intraarterial chemoinfusions, 20 patients (71.4% received two infusions, and eight patients (28.6% received three infusions. One patient (3.6% had CR and 23 (82.1% had PR. The total effectiveness rate (CR and PR was 85.7% (24/28. All stage 3 patients underwent Phase II surgical resection after chemoinfusion, and the surgical resection participation rate was 100% (26/26. The mean time from the first chemoinfusion to surgery was 2 ± 1.2 months. Two patients with stage 4 cancer died of distant metastasis and cachexia, and the remaining 26 patients were still alive.Conclusion: Intraarterial chemoinfusion is a safe and effective therapy, achieving down-staging in a relatively short period for locally advanced breast cancer.Keywords: advanced breast cancer, intraarterial infusion, chemotherapy, therapeutic effect

  5. Locally advanced rectal cancer: diffusion-weighted MR tumour volumetry and the apparent diffusion coefficient for evaluating complete remission after preoperative chemoradiation therapy

    Energy Technology Data Exchange (ETDEWEB)

    Ha, Hong Il [University of Ulsan College of Medicine, Asan Medical Center, Department of Radiology and Research Institute of Radiology, Seoul (Korea, Republic of); Hallym University Medical Center, Hallym University Sacred Heart Hospital, Department of Radiology, Anyang-si, Gyeonggi-do (Korea, Republic of); Kim, Ah Young; Park, Seong Ho; Ha, Hyun Kwon [University of Ulsan College of Medicine, Asan Medical Center, Department of Radiology and Research Institute of Radiology, Seoul (Korea, Republic of); Yu, Chang Sik [University of Ulsan College of Medicine, Asan Medical Center, Department of Colon and Rectal Surgery, Seoul (Korea, Republic of)

    2013-12-15

    To evaluate DW MR tumour volumetry and post-CRT ADC in rectal cancer as predicting factors of CR using high b values to eliminate perfusion effects. One hundred rectal cancer patients who underwent 1.5-T rectal MR and DW imaging using three b factors (0, 150, and 1,000 s/mm{sup 2}) were enrolled. The tumour volumes of T2-weighted MR and DW images and pre- and post-CRT ADC{sub 150-1000} were measured. The diagnostic accuracy of post-CRT ADC, T2-weighted MR, and DW tumour volumetry was compared using ROC analysis. DW MR tumour volumetry was superior to T2-weighted MR volumetry comparing the CR and non-CR groups (P < 0.001). Post-CRT ADC showed a significant difference between the CR and non-CR groups (P = 0.001). The accuracy of DW tumour volumetry (A{sub z} = 0.910) was superior to that of T2-weighed MR tumour volumetry (A{sub z} = 0.792) and post-CRT ADC (A{sub z} = 0.705) in determining CR (P = 0.015). Using a cutoff value for the tumour volume reduction rate of more than 86.8 % on DW MR images, the sensitivity and specificity for predicting CR were 91.4 % and 80 %, respectively. DW MR tumour volumetry after CRT showed significant superiority in predicting CR compared with T2-weighted MR images and post-CRT ADC. (orig.)

  6. Radiation induced apoptosis and initial DNA damage are inversely related in locally advanced breast cancer patients

    Directory of Open Access Journals (Sweden)

    Rodriguez-Gallego Carlos

    2010-09-01

    Full Text Available Abstract Background DNA-damage assays, quantifying the initial number of DNA double-strand breaks induced by radiation, have been proposed as a predictive test for radiation-induced toxicity. Determination of radiation-induced apoptosis in peripheral blood lymphocytes by flow cytometry analysis has also been proposed as an approach for predicting normal tissue responses following radiotherapy. The aim of the present study was to explore the association between initial DNA damage, estimated by the number of double-strand breaks induced by a given radiation dose, and the radio-induced apoptosis rates observed. Methods Peripheral blood lymphocytes were taken from 26 consecutive patients with locally advanced breast carcinoma. Radiosensitivity of lymphocytes was quantified as the initial number of DNA double-strand breaks induced per Gy and per DNA unit (200 Mbp. Radio-induced apoptosis at 1, 2 and 8 Gy was measured by flow cytometry using annexin V/propidium iodide. Results Radiation-induced apoptosis increased in order to radiation dose and data fitted to a semi logarithmic mathematical model. A positive correlation was found among radio-induced apoptosis values at different radiation doses: 1, 2 and 8 Gy (p Conclusions An inverse association was observed for the first time between these variables, both considered as predictive factors to radiation toxicity.

  7. Side effects of bone-targeted therapies in advanced breast cancer.

    Science.gov (United States)

    Domschke, Christoph; Schuetz, Florian

    2014-10-01

    In up to 75% of cases, advanced breast cancer patients eventually develop bone metastases with often debilitating skeletal-related events (SREs). Osteoclast inhibitors are commonly used as therapeutic mainstay with clinical studies showing superiority of denosumab over bisphosphonates (e.g., zoledronate) for the prevention of SREs. The present review discusses the adverse event profile of these agents, and addresses the prevention and management of untoward side effects. Adverse events associated with osteoclast inhibitors comprise osteonecrosis of the jaw and hypocalcemia. Hypocalcemia is more common with denosumab, particularly in severe renal dysfunction. During therapy, the appropriate prevention of these adverse events includes close attention to dental health, avoidance of invasive dental procedures, supplementation with calcium and vitamin D unless patients are hypercalcemic, and regular monitoring of relevant serum values. Relating to the risk of nephrotoxicity, bisphosphonates but not denosumab have been incriminated. Therefore, serum creatinine levels should be checked prior to each dose of zoledronate, and in severe renal dysfunction (creatinine clearance < 30 ml/min) zoledronate is contraindicated anyway. Acute-phase reactions are particularly linked to bisphosphonates. Consequently, if these adverse events predominate, switching to denosumab is recommended. PMID:25759613

  8. Palliative home care intervention to improve the quality of life of women with advanced breast cancer

    International Nuclear Information System (INIS)

    The quality of life is affected frequently observed in women with advanced breast cancer and is considered a leading indicator of effectiveness of palliative care. A descriptive, quasi-experimental study is presented ex-ante / ex-post, by applying open-ended interviews to explore the effects on the processes of adaptation of each patient and a self-administrable scale identified specific dimensions of quality of life, satisfaction with care and overall quality of life. The intervention was performed palliative home care to 52 women, according to the damages identified in the baseline diagnosis. The overall strategy included four steps: clinical and socio-demographic characterization of women; identification of the effects on the processes of adaptation by the theoretical model of Roy and dimensions of quality of life frequently affected, to design individually oriented actions on the drive shaft of Nursing Interventions Classification and evaluation of results intervention. The dimensions achieved higher frequency of involvement were: behavior, physical symptoms, pain interference and leisure activities, social life and family. Data were analyzed with qualitative methodologies and uni and multivariate statistical processing. After the intervention favorable changes in adaptive processes and dimensions of quality of life were observed; well as in the assessment of overall satisfaction with life. It was interesting that the dimensions of satisfaction assessed at the end of the intervention obtained an unfavorable assessment, outcome associated with sociodemographic variables. (author)

  9. Recent Advances in the Use of Metformin: Can Treating Diabetes Prevent Breast Cancer?

    Directory of Open Access Journals (Sweden)

    Diana Hatoum

    2015-01-01

    Full Text Available There is substantial epidemiological evidence pointing to an increased incidence of breast cancer and morbidity in obese, prediabetic, and diabetic patients. In vitro studies strongly support metformin, a diabetic medication, in breast cancer therapy. Although metformin has been heralded as an exciting new breast cancer treatment, the principal consideration is whether metformin can be used as a generic treatment for all breast cancer types. Importantly, will metformin be useful as an inexpensive therapy for patients with comorbidity of diabetes and breast cancer? In general, meta-analyses of clinical trial data from retrospective studies in which metformin treatment has been used for patients with diabetes and breast cancer have a positive trend; nevertheless, the supporting clinical data outcomes remain inconclusive. The heterogeneity of breast cancer, confounded by comorbidity of disease in the elderly population, makes it difficult to determine the actual benefits of metformin therapy. Despite the questionable evidence available from observational clinical studies and meta-analyses, randomized phases I–III clinical trials are ongoing to test the efficacy of metformin for breast cancer. This special issue review will focus on recent research, highlighting in vitro research and retrospective observational clinical studies and current clinical trials on metformin action in breast cancer.

  10. Recent advances in the use of metformin: can treating diabetes prevent breast cancer?

    Science.gov (United States)

    Hatoum, Diana; McGowan, Eileen M

    2015-01-01

    There is substantial epidemiological evidence pointing to an increased incidence of breast cancer and morbidity in obese, prediabetic, and diabetic patients. In vitro studies strongly support metformin, a diabetic medication, in breast cancer therapy. Although metformin has been heralded as an exciting new breast cancer treatment, the principal consideration is whether metformin can be used as a generic treatment for all breast cancer types. Importantly, will metformin be useful as an inexpensive therapy for patients with comorbidity of diabetes and breast cancer? In general, meta-analyses of clinical trial data from retrospective studies in which metformin treatment has been used for patients with diabetes and breast cancer have a positive trend; nevertheless, the supporting clinical data outcomes remain inconclusive. The heterogeneity of breast cancer, confounded by comorbidity of disease in the elderly population, makes it difficult to determine the actual benefits of metformin therapy. Despite the questionable evidence available from observational clinical studies and meta-analyses, randomized phases I-III clinical trials are ongoing to test the efficacy of metformin for breast cancer. This special issue review will focus on recent research, highlighting in vitro research and retrospective observational clinical studies and current clinical trials on metformin action in breast cancer. PMID:25866793

  11. Advancements in Imaging Technology for Detection and Diagnosis of Palpable Breast Masses.

    Science.gov (United States)

    Jaeger, Barbara M; Hong, Andrea S; Letter, Haley; Odell, Matthew C

    2016-06-01

    Breast cancer is the most commonly diagnosed cancer among women worldwide and the most common cause of cancer death in women. The most common presentation of breast cancer is the presence of a palpable mass, whether noted by the patient during breast self-examination or noted during clinical breast examination. There are a variety of imaging modalities now available for the evaluation of a palpable abnormality. A thorough understanding of the indications, risks, and benefits can help the clinician guide the patient through an appropriate, comprehensive imaging work up. PMID:27101239

  12. Recent Advances in the Use of Metformin: Can Treating Diabetes Prevent Breast Cancer?

    Science.gov (United States)

    McGowan, Eileen M.

    2015-01-01

    There is substantial epidemiological evidence pointing to an increased incidence of breast cancer and morbidity in obese, prediabetic, and diabetic patients. In vitro studies strongly support metformin, a diabetic medication, in breast cancer therapy. Although metformin has been heralded as an exciting new breast cancer treatment, the principal consideration is whether metformin can be used as a generic treatment for all breast cancer types. Importantly, will metformin be useful as an inexpensive therapy for patients with comorbidity of diabetes and breast cancer? In general, meta-analyses of clinical trial data from retrospective studies in which metformin treatment has been used for patients with diabetes and breast cancer have a positive trend; nevertheless, the supporting clinical data outcomes remain inconclusive. The heterogeneity of breast cancer, confounded by comorbidity of disease in the elderly population, makes it difficult to determine the actual benefits of metformin therapy. Despite the questionable evidence available from observational clinical studies and meta-analyses, randomized phases I–III clinical trials are ongoing to test the efficacy of metformin for breast cancer. This special issue review will focus on recent research, highlighting in vitro research and retrospective observational clinical studies and current clinical trials on metformin action in breast cancer. PMID:25866793

  13. A structured review of health utility measures and elicitation in advanced/metastatic breast cancer

    Science.gov (United States)

    Hao, Yanni; Wolfram, Verena; Cook, Jennifer

    2016-01-01

    Background Health utilities are increasingly incorporated in health economic evaluations. Different elicitation methods, direct and indirect, have been established in the past. This study examined the evidence on health utility elicitation previously reported in advanced/metastatic breast cancer and aimed to link these results to requirements of reimbursement bodies. Methods Searches were conducted using a detailed search strategy across several electronic databases (MEDLINE, EMBASE, Cochrane Library, and EconLit databases), online sources (Cost-effectiveness Analysis Registry and the Health Economics Research Center), and web sites of health technology assessment (HTA) bodies. Publications were selected based on the search strategy and the overall study objectives. Results A total of 768 publications were identified in the searches, and 26 publications, comprising 18 journal articles and eight submissions to HTA bodies, were included in the evidence review. Most journal articles derived utilities from the European Quality of Life Five-Dimensions questionnaire (EQ-5D). Other utility measures, such as the direct methods standard gamble (SG), time trade-off (TTO), and visual analog scale (VAS), were less frequently used. Several studies described mapping algorithms to generate utilities from disease-specific health-related quality of life (HRQOL) instruments such as European Organization for Research and Treatment of Cancer Quality of Life Questionnaire – Core 30 (EORTC QLQ-C30), European Organization for Research and Treatment of Cancer Quality of Life Questionnaire – Breast Cancer 23 (EORTC QLQ-BR23), Functional Assessment of Cancer Therapy – General questionnaire (FACT-G), and Utility-Based Questionnaire-Cancer (UBQ-C); most used EQ-5D as the reference. Sociodemographic factors that affect health utilities, such as age, sex, income, and education, as well as disease progression, choice of utility elicitation method, and country settings, were identified

  14. Recent advances in microvascular autologous breast reconstruction after ablative tumor surgery.

    Science.gov (United States)

    Pollhammer, Michael S; Duscher, Dominik; Schmidt, Manfred; Huemer, Georg M

    2016-02-10

    Breast cancer is a ubiquitous disease and one of the leading causes of death in women in western societies. With overall increasing survival rates, the number of patients who need post-mastectomy reconstruction is on the rise. Especially since its psychological benefits have been broadly recognized, breast reconstruction has become a key component of breast cancer treatment. Evolving from the early beginnings of breast reconstruction with synthetic implants in the 1960s, microsurgical tissue transfer is on the way to become the gold standard for post oncology restoration of the breast. Particularly since the advent of perforator based free flap surgery, free tissue transfer has become as safe option for breast reconstruction with low morbidity. The lower abdominal skin and subcutaneous fat tissue typically offer enough volume to create an aesthetically satisfying breast mound. Nowadays, the most commonly used flap from this donor site is the deep inferior epigastric artery perforator flap. If the lower abdomen is not available as a donor site, the gluteal area and thigh provide a number of flaps suitable for breast reconstruction. If the required breast volume is small, and there is enough tissue available on the upper medial thigh, then a transverse upper gracilis flap may be a practicable method to reconstruct the breast. In case of a higher amount of required volume, a gluteal artery perforator flap is the best choice. However, what is crucial in addition to selecting the best flap option for the individual patient is the timing of the operation. In patients with confirmed post-mastectomy radiation therapy, it is advisable to perform microvascular breast reconstruction only in a delayed fashion. PMID:26862495

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

    LENUS (Irish Health Repository)

    Caiazza, F

    2011-01-18

    The eicosanoid signalling pathway promotes the progression of malignancies through the production of proliferative prostaglandins (PGs). Cytosolic phospholipase A(2)α (cPLA(2)α) activity provides the substrate for cyclooxygenase-dependent PG release, and we have previously found that cPLA(2)α expression correlated with EGFR\\/HER2 over-expression in a small number of breast cancer cell lines.

  16. 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

  17. Advances in Translational Medicine of Breast Cancer: From Bench to Bedside

    Directory of Open Access Journals (Sweden)

    Xin-en HUANG

    2015-03-01

    Full Text Available Breast cancer is one of the most common malignant tumors in women, and its incidence increases year by year. With the rapid development of human genomics, proteomics and bioinformatics, the basic and clinical results of breast cancer have emerged in endlessly. Translational medicine is a hot field of international medicine, biological interdisciplinary science and many research funding projects at present, committed to establishing an academic exchange platform for global scientific researchers. In this study, the translational medicine of breast cancer was summarized and reviewed from the following aspects, including molecular markers related to breast cancer, molecular typing, individualized and molecular targeted therapies, relationship between molecular biology and imagiology of breast cancer.

  18. Surgical management of epithelial parotid tumours

    International Nuclear Information System (INIS)

    FNAC. Superficial parotidectomy (SP) was the operation of choice. Facial nerve can be saved in total conservative parotidectomy for benign tumour in deep lobe and early malignant tumour. Radical parotidectomy followed by radiotherapy and in selected cases neck node dissection is the recommended procedures for advanced malignant parotid tumours. (author)

  19. Hereditary breast cancer: ever more pieces to the polygenic puzzle.

    Science.gov (United States)

    Bogdanova, Natalia; Helbig, Sonja; Dörk, Thilo

    2013-01-01

    Several susceptibility genes differentially impact on the lifetime risk for breast cancer. Technological advances over the past years have enabled the detection of genetic risk factors through high-throughput screening of large breast cancer case-control series. High- to intermediate penetrance alleles have now been identified in more than 20 genes involved in DNA damage signalling and repair, and more than 70 low-penetrance loci have been discovered through recent genome-wide association studies. In addition to classical germ-line mutation and single-nucleotide polymorphism, copy number variation and somatic mosaicism have been proposed as potential predisposing mechanisms. Many of the identified loci also appear to influence breast tumour characteristics such as estrogen receptor status. In this review, we briefly summarize present knowledge about breast cancer susceptibility genes and discuss their implications for risk prediction and clinical practice. PMID:24025454

  20. Radiation induced apoptosis and initial DNA damage are inversely related in locally advanced breast cancer patients

    International Nuclear Information System (INIS)

    DNA-damage assays, quantifying the initial number of DNA double-strand breaks induced by radiation, have been proposed as a predictive test for radiation-induced toxicity. Determination of radiation-induced apoptosis in peripheral blood lymphocytes by flow cytometry analysis has also been proposed as an approach for predicting normal tissue responses following radiotherapy. The aim of the present study was to explore the association between initial DNA damage, estimated by the number of double-strand breaks induced by a given radiation dose, and the radio-induced apoptosis rates observed. Peripheral blood lymphocytes were taken from 26 consecutive patients with locally advanced breast carcinoma. Radiosensitivity of lymphocytes was quantified as the initial number of DNA double-strand breaks induced per Gy and per DNA unit (200 Mbp). Radio-induced apoptosis at 1, 2 and 8 Gy was measured by flow cytometry using annexin V/propidium iodide. Radiation-induced apoptosis increased in order to radiation dose and data fitted to a semi logarithmic mathematical model. A positive correlation was found among radio-induced apoptosis values at different radiation doses: 1, 2 and 8 Gy (p < 0.0001 in all cases). Mean DSB/Gy/DNA unit obtained was 1.70 ± 0.83 (range 0.63-4.08; median, 1.46). A statistically significant inverse correlation was found between initial damage to DNA and radio-induced apoptosis at 1 Gy (p = 0.034). A trend toward 2 Gy (p = 0.057) and 8 Gy (p = 0.067) was observed after 24 hours of incubation. An inverse association was observed for the first time between these variables, both considered as predictive factors to radiation toxicity

  1. Randomized phase II trial on mitomycin-C/cisplatin +/- KLT in heavily pretreated advanced breast cancer.

    Science.gov (United States)

    Guo, H Y; Cai, Y; Yang, X M; Wang, Z H; Wang, J L; Zhao, X M; Li, J; Hu, X C

    2008-01-01

    A randomized phase II study using mitomycin (MMC)/cisplatin (DDP) regimen with or without Kanglaite (KLT, a traditional Chinese medicine) as salvage treatment was conducted to exploit KLT's potential effects on patients with advanced breast cancer (ABC). Triweekly regimen consisted of mitomycin (8 mg/m(2)) administered intravenously on day 1, and cisplatin (25 mg/m(2)) intravenously on days 1 to 3. KLT (100 ml) was given intravenously per day on days 1 to 14 every 3 weeks. Between April 2006 and July 2007, 60 patients with a median age of 48 years were randomized into MMC/DDP with or without KLT treatment. In all, the objective response rate (ORR) was 17.5%. There were no significant differences between experimental and control treatments in terms of ORR (14.3% vs. 20.7%, p = 0.730), clinical benefit rates (24.1% vs. 28.6%, p = 0.468), median time to progression (TTP; 3.63 vs. 4.0, p = 0.872), and overall survival (OS; 7.17 vs. not reached, p = 0.120). The median TTP for patients with complete or partial responses was 6.0 months, but only 2.1 months for patients with stable or progressive disease (SD or PD; p = 0.028). While the median OS for patients who obtained clinical benefit from chemotherapy was not reached, that of patients with SD of no more than 6 months or PD was only 7.17 months (p = 0.004). There is no additional benefit when KLT is added to the MMC/DDP doublet in the management of ABC. Patients who obtained clinical benefit from chemotherapy had a longer TTP and OS. PMID:18711764

  2. The Role of Genomic Profiling in Advanced Breast Cancer: The Two Faces of Janus

    Science.gov (United States)

    Eralp, Yesim

    2016-01-01

    Recent advances in genomic technology have led to considerable improvement in our understanding of the molecular basis that underpins breast cancer biology. Through the use of comprehensive whole genome genomic profiling by next-generation sequencing, an unprecedented bulk of data on driver mutations, key genomic rearrangements, and mechanisms on tumor evolution has been generated. These developments have marked the beginning of a new era in oncology called “personalized or precision medicine.” Elucidation of biologic mechanisms that underpin carcinogenetic potential and metastatic behavior has led to an inevitable explosion in the development of effective targeted agents, many of which have gained approval over the past decade. Despite energetic efforts and the enormous support gained within the oncology community, there are many obstacles in the clinical implementation of precision medicine. Other than the well-known biologic markers, such as ER and Her-2/neu, no proven predictive marker exists to determine the responsiveness to a certain biologic agent. One of the major issues in this regard is teasing driver mutations among the background noise within the bulk of coexisting passenger mutations. Improving bioinformatics tools through electronic models, enhanced by improved insight into pathway dependency may be the step forward to overcome this problem. Next, is the puzzle on spatial and temporal tumoral heterogeneity, which remains to be solved by ultra-deep sequencing and optimizing liquid biopsy techniques. Finally, there are multiple logistical and financial issues that have to be meticulously tackled in order to optimize the use of “precision medicine” in the real-life setting. PMID:27547031

  3. Neoadjuvant chemotherapy in patients with locally advanced breast cancer: A pilot-observational study

    Directory of Open Access Journals (Sweden)

    Hardik G Dodiya

    2015-01-01

    Full Text Available Background: Locally advanced breast cancer (LABC remains major clinical issue with regard to selection and duration of therapy since many years. Neoadjuvant chemotherapy (NACT is multimodality program, established to treat LABC. Many research tasks are ongoing to develop specific neoadjuvant chemotherapy regimen with specific duration to improve long-term control of LABC. Patients and Methods: Forty-seven patients diagnosed with LABC were Included and analyzed to compare the outcomes [pathological complete response (pCR, clinical response, overall response rate (ORR, disease control rate, overall survival and progression-free survival]. These patients treated with either combination of anthracycline and taxane-based chemotherapy or anthracycline-based chemotherapy. Results: There was no any statistical significance with respect to demographic data treated of patients between two arms (P > 0.05. Patients underwent TAC chemotherapy had pCR 20.8% whereas FAC/FEC chemotherapy patients had pCR 13% (P = 0.48. Higher ORR was noted in TAC chemotherapy arm (75% when compared with FAC/FEC chemotherapy arm (60.9% (P = 0.29. The study also shows better disease control rate in TAC chemotherapy arm (95.8% as compared to FAC/FEC chemotherapy arm (82.6%. There was no statistical significance in overall survival (P = 0.31 and progression-free survival (P = 0.51 between two arms. Conclusion: Despite of the superiority of combination of anthracycline and taxane-based chemotherapy over the anthracycline-based chemotherapy in the present study, further pivotal studies should be conducted to confirm the combination of anthracycline and taxane-based chemotherapy as a better neoadjuvant regimen for treatment of LABC tumors.

  4. Tumours and tumourous diseases; Tumoren, tumoraehnliche Erkrankungen

    Energy Technology Data Exchange (ETDEWEB)

    Winkelmann, W. (ed.)

    2005-07-01

    This book on tumours and tumourous diseases comprises two parts: 1. Bone tumours and tumourous lesions. 2. Soft tissue tumours and tumourous lesions. Details are presented on pathology, diagnosis, conservative and perioperative therapy, surgical therapy, complications after resection, indicators for amputation, recommendations for follow-up treatment, radiotherapy, radionuclide therapy, alternative therapies, therapy concepts in case of metastases, tissue engineering and plastic surgery. (uke) [German] Der vorliegende Band der Reihe Orthopaedie und orthopaedische Chirurgie behandelt das Thema Tumoren und tumoraehnliche Erkrankungen. Der Band teilt sich in zwei Kapitel: 1. Knochentumoren und tumorartige Laesionen und 2. Weichteiltumoren und tumorartige Laesionen. Dargestellt werden Pathologie, Diagnostik, konservative und perioperative Therapie, chirurgische Therapie, Komplikationen nach Resektion, Indikatoren zur Amputation, Nachsorgeempfehlung, Strahlentherapie, Radionuklidtherapie, alternative Therapieverfahren, Therapiekonzepte bei Metastasen, Tissue Engineering und plastisch-chirurgische Massnahmen. (uke)

  5. Mast cells and eosinophils in invasive breast carcinoma

    International Nuclear Information System (INIS)

    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

  6. 乳腺癌列线图模型的研究进展%Advances in breast cancer related nomograms

    Institute of Scientific and Technical Information of China (English)

    姚儒; 潘博; 孙强; 徐颖; 王常珺; 周易冬; 茅枫; 林燕

    2013-01-01

    Breast cancer is the leading cause of malignancy-related mortality in women worldwide. The more accurate prediction of lymph node metastasis and evaluation of personalized prognosis of breast cancer patients could provide evidence and reference for individualized comprehensive treatment and clinical decision-making. Nomogram is statistical calculation model developed to generate individualized prediction of a certain clinical event through the factors associated with it. Currently breast cancer related nomogram models is most commonly used in the prediction of non-sentinel lymph node status in patients with sentinel lymph node-positive breast cancer, sentinel lymph node metastasis in clinical node-negative breast cancer and prognosis evaluation of breast cancer. This article reviewed the recent advances in breast cancer related nomograms according to the above mentioned three aspects, and evaluated respectively the predictive factors, accuracy, characteristics and clinical application potential.%乳腺癌是危害全世界女性健康最常见的恶性肿瘤,对乳腺癌患者淋巴结转移情况及个体化预后进行评估预测,可为个体化综合治疗方案的制定以及临床决策提供参考依据。列线图模型(nomogram)可通过各种预测因素量化临床事件风险。从nomogram在前哨淋巴结阳性患者非前哨淋巴结转移预测、早期乳腺癌前哨淋巴结转移预测以及乳腺癌个体化预后预测等3个方面,分别评价其预测因素、应用特点以及预测的准确性等指标,以期在未来的工作中,通过选择更合理的预测因素、调整不同预测因素所占权重,以建立、改良能更好地应用于临床预测的nomogram模型,为制定临床决策提供参考依据。现就乳腺癌相关列线图模型的最新研究进展作一综述。

  7. Feasibility of breast conservation surgery in locally advanced breast cancer downstaged by neoadjuvant chemotherapy: A study in mastectomy specimens using simulation lumpectomy

    Directory of Open Access Journals (Sweden)

    Viswambharan Jaiganesh

    2005-01-01

    Full Text Available BACKGROUND : The response of locally advanced breast cancer (LABC to neoadjuvant chemotherapy (NACT offers these patients previously treated by mastectomy, the chance for breast conservation. AIM : This study aims to assess the feasibility of lumpectomy in patients with LABC treated by NACT, with residual tumor 5 cm. SETTINGS, DESIGN : Single group prospective study from August 2001 to June 2003 in a teaching hospital. MATERIALS AND METHODS : Thirty patients with LABC whose tumors reduced with NACT to 5 cm were included. Simulation lumpectomy was performed on the mastectomy specimens to achieve 1 to 2 cm clearance from tumor and hence margin negativity. Multiple sections of the inked margin were studied. STATISTICAL ANALYSIS : Margin positivity was correlated with patient factors. Chi square test and Fisher′s exact test used as appropriate. P value 0.05 was considered significant. RESULTS AND CONCLUSIONS : After three cycles of NACT, 4 patients (13% had complete clinical response including 2 with complete pathological response. Twenty-two (73% showed partial response and 4, no response. Fourteen out of thirty (47% had tumor involvement of margins. Tumors with post-chemotherapy size> 4 cm were margin positive in 10/13 (77%. Tumors with post-chemotherapy size>3 cm were margin positive in 13/24 (54%. Tumors with post-chemotherapy size 3 cm were margin negative in 5/6 (83%. Pre-chemotherapy tumor size and post-chemotherapy tumor size were significantly associated with margin positivity (P=0.003. Tumors in the subareolar location had significantly higher incidence of residual tumor in the nipple areola complex. (P=0.04. Margin positivity of lumpectomy on downstaged tumors can be reduced by removing the nipple areola complex in subareolar tumors and by limiting breast conservation to tumors with post-chemotherapy size 3 cm.

  8. Feasibility of breast conservation surgery in locally advanced breast cancer downstaged by neoadjuvant chemotherapy: A study in mastectomy specimens using simulation lumpectomy

    Directory of Open Access Journals (Sweden)

    Viswambharan Jaiganesh

    2005-01-01

    Full Text Available BACKGROUND: The response of locally advanced breast cancer (LABC to neoadjuvant chemotherapy (NACT offers these patients previously treated by mastectomy, the chance for breast conservation. AIM: This study aims to assess the feasibility of lumpectomy in patients with LABC treated by NACT, with residual tumor 5 cm. SETTINGS, DESIGN: Single group prospective study from August 2001 to June 2003 in a teaching hospital. MATERIALS AND METHODS: Thirty patients with LABC whose tumors reduced with NACT to 5 cm were included. Simulation lumpectomy was performed on the mastectomy specimens to achieve 1 to 2 cm clearance from tumor and hence margin negativity. Multiple sections of the inked margin were studied. STATISTICAL ANALYSIS: Margin positivity was correlated with patient factors. Chi square test and Fisher′s exact test used as appropriate. P value 0.05 was considered significant. RESULTS AND CONCLUSIONS: After three cycles of NACT, 4 patients (13% had complete clinical response including 2 with complete pathological response. Twenty-two (73% showed partial response and 4, no response. Fourteen out of thirty (47% had tumor involvement of margins. Tumors with post-chemotherapy size >4 cm were margin positive in 10/13 (77%. Tumors with post-chemotherapy size>3 cm were margin positive in 13/24 (54%. Tumors with post-chemotherapy size 3 cm were margin negative in 5/6 (83%. Pre-chemotherapy tumor size and post-chemotherapy tumor size were significantly associated with margin positivity (P=0.003. Tumors in the subareolar location had significantly higher incidence of residual tumor in the nipple areola complex. (P=0.04. Margin positivity of lumpectomy on downstaged tumors can be reduced by removing the nipple areola complex in subareolar tumors and by limiting breast conservation to tumors with post-chemotherapy size 3 cm.

  9. The two aspects of tumour hypoxia

    International Nuclear Information System (INIS)

    Hypoxia is a therapeutic problem as it renders solid tumours resistant to sparsely ionizing radiation and some forms of chemotherapy. At present it is postulated that tumour hypoxia induces two types of reactions. On the one hand tissue O2 concentration 2 2 0.5-20 mm Hg), not severely, hypoxic cells may be of the greatest importance in determining biological resistance. The methods of assessing hypoxia currently applied in clinical practice are not satisfactory. However, recent advances in imaging technologies suggest that in the near future it might be possible to track temporal changes in O2 level and acute and chronic hypoxic tumour sub fractions. The ultimate goal is understanding tumour biology basing on the clinical bio markers that reflect hypoxia-associated genetic or proteomic signatures in tumour cells, in order to individualize therapy. (authors)

  10. Radiation therapy planning with photons and protons for early and advanced breast cancer: an overview

    Directory of Open Access Journals (Sweden)

    Lomax Antony J

    2006-07-01

    Full Text Available Abstract Postoperative radiation therapy substantially decreases local relapse and moderately reduces breast cancer mortality, but can be associated with increased late mortality due to cardiovascular morbidity and secondary malignancies. Sophistication of breast irradiation techniques, including conformal radiotherapy and intensity modulated radiation therapy, has been shown to markedly reduce cardiac and lung irradiation. The delivery of more conformal treatment can also be achieved with particle beam therapy using protons. Protons have superior dose distributional qualities compared to photons, as dose deposition occurs in a modulated narrow zone, called the Bragg peak. As a result, further dose optimization in breast cancer treatment can be reasonably expected with protons. In this review, we outline the potential indications and benefits of breast cancer radiotherapy with protons. Comparative planning studies and preliminary clinical data are detailed and future developments are considered.

  11. Possibility of conservative local treatment after combined chemotherapy and preoperative irradiation for locally advanced noninflammatory breast cancer

    International Nuclear Information System (INIS)

    Purpose: The aims of this prospective study were to evaluate the outcome and the possibility of breast conservation therapy for patients with locally advanced noninflammatory breast cancer after primary chemotherapy followed by external preoperative irradiation. Methods and Materials: Between April 1982 and June 1990, 97 patients with locally advanced nonmetastatic and noninflammatory breast cancer were treated. The median follow-up was 93 months from the beginning of treatment. The induction treatment consisted of four courses of chemotherapy (doxorubicin, vincristine, cyclophosphamide, 5-fluorouracil) followed by preoperative irradiation (45 Gy to the breast and nodal areas). A fifth course of chemotherapy was given after radiation therapy. Three different loco-regional approaches were proposed, depending on the tumoral response. In 37 patients (38%) with residual tumor larger than 3 cm in diameter or located behind the nipple or with bifocal tumors, mastectomy and axillary dissection were performed. Sixty other patients (62%) benefited from conservative treatment: 33 patients (34%) achieved complete remission and no surgery was done but additional radiation boost was given to the initial tumor bed; 27 patients (28%) who had a residual mass less than or equal to 3 cm in diameter were treated by wide excision and axillary dissection followed by a boost to the excision site. After completion of local therapy, all patients received a sixth course of chemotherapy. A maintenance adjuvant chemotherapy regimen without anthracycline was prescribed (12 monthly cycles). Results: The 5-year actuarial loco-regional relapse rate was 16% after radiotherapy alone, 16% following wide excision and radiotherapy, and 5.4% following mastectomy. The 5-year loco-regional relapse rate was significantly higher after conservative local treatment (wide excision and radiotherapy, and radiotherapy alone) than after mastectomy (p = 0.04). After conservative local treatment, the 5-year breast

  12. Advancement flaps are enough in most cases as onco plastic technique for breast cancer even with central or periareolar localisation

    International Nuclear Information System (INIS)

    I have read with great interest khafagy et all s article in ENC1 2012:24:91-6 This small series needs explanations for following questions: 1- Thirteen cases with N0 have been operated by a complete axillary dissection. Would it be better to undertake sentinel lymph node biopsy (SLNB) in these cases? 2- The patients with periareolar tumor localization (half of the patients) underwent needlessly a pedicled flap operation instead of an advancement flap or simple rotation flap. They are simple and therefore less time-consuming onco plastic procedures. They do not require whole nippleareola complex excision. Therefore, advancement flaps or periareolar mastopexy [1] were more reasonable. 3- Ten patients with N2 represent locally advanced cancer of breast (Stage III). They should be treated by primary chemotherapy instead of surgery first. It needs explanation. 4- Four cases with N+ have not been given adjuvant chemotherapy. It should be explained. 5- The rates of good cosmetic results were the same for both patients and doctors. But in the literature, the rates of health professionals are nearly always lower than patients [2], It needs explanation. 6- The condition of contralateral breasts has not been presented. Is not there some cases requiring contralateral mastoplasty, reduction or any other cosmetic procedure? Kind regards.

  13. Patients’ preferences and willingness-to-pay for postmenopausal hormone receptor-positive, HER2-negative advanced breast cancer treatments after failure of standard treatments

    OpenAIRE

    Ngorsuraches, Surachat; Thongkeaw, Klangjai

    2015-01-01

    Patients’ preferences increasingly play roles in cancer treatments. The objective of this study is to examine breast cancer patients’ preferences and willingness-to-pay (WTP) for postmenopausal hormone receptor-positive, HER2-negative advanced breast cancer treatments after failure of standard treatments. Four attributes, i.e. progression free survival (PFS), anemia, pneumonitis, and cost, and their levels of exemestane and exemestane plus everolimus from literature and patient interviews wer...

  14. Outcome of combined modality treatment including neoadjuvant chemotherapy of 128 cases of locally advanced breast cancer: Data from a tertiary cancer center in northern India

    OpenAIRE

    Raina, V.; M Kunjahari; N K Shukla; SVS Deo; Sharma, A.; Mohanti, B. K.; D N Sharma

    2011-01-01

    Background: Breast cancer is now the most common cancer in many parts of India and the incidence varies from 12 to 31/100000, and is rising. Locally advanced breast cancer (LABC) accounts for 30 - 35% of all cases of breast cancers in India. LABC continues to present a challenge and imposes a major health impact in our country. Materials and Methods: We carried out a analysis of our LABC patients who received neoadjuvant chemotherapy (NACT) at our hospital over a 10-year period, from January ...

  15. Ablation of lung tumours

    OpenAIRE

    Gillams, Alice

    2012-01-01

    Abstract Radiofrequency, laser, microwave and cryotherapy have all been used for the ablation of lung tumours. However, radiofrequency ablation (RFA) and microwave ablation are the most widely used technologies. RFA has been successfully applied to tumour measuring from

  16. The localisation and micro-mapping of copper and other trace elements in breast tumours using a synchrotron micro-XRF system

    International Nuclear Information System (INIS)

    Trace elements have critical roles in cancer biology. The quantity and distribution of the elements Cl, Ca, K, P, S, Ti, Fe, Cu and Zn in samples of primary breast cancer have been assessed. The samples were formalin fixed tissue specimens formatted as microarrays of cores 1.0 mm diameter and 10 μm thick each. The data were obtained using a synchrotron X-ray fluorescence microprobe system. The spatial resolution of elemental maps was approximately 20 μm. Maps were compared with light transmission images of the samples and then the images were stained for cancer. The synchrotron system proved successful in producing data that could be mapped into high-resolution images where clear structure could be identified. Correlation of these distributions with the concentrations of cancer cells was achieved in some samples

  17. Clinical implications of recent studies using mTOR inhibitors to treat advanced hormone receptor-positive breast cancer

    International Nuclear Information System (INIS)

    Breast cancer is a leading cause of cancer-related death worldwide. Approximately 75% of breast cancer is hormone receptor-positive (HR+) and is managed with endocrine therapies. However, relapse or disease progression caused by primary or acquired endocrine resistance is frequent. Phosphatidylinositol-3-kinase (PI3K)/protein kinase B (Akt)/mammalian target of rapamycin (mTOR)-mediated signaling is one of the molecular mechanisms leading to endocrine resistance. mTOR inhibitors that target the PI3K/Akt/mTOR pathway are the first of the targeted therapies to be evaluated in clinical trials to overcome endocrine resistance. Although the clinical trial with temsirolimus, an mTOR inhibitor, did not show any benefit when compared with endocrine therapy alone, a Phase II clinical trial with sirolimus has been promising. Recently, everolimus was approved in combination with exemestane by the US Food and Drug Administration for treating postmenopausal women with advanced HR+ breast cancer, based on the results of a Phase III trial. Therefore, everolimus represents the first and only targeted agent approved for combating endocrine resistance

  18. Cardiac tumours in children

    Directory of Open Access Journals (Sweden)

    Parsons Jonathan M

    2007-03-01

    Full Text Available Abstract Cardiac tumours are benign or malignant neoplasms arising primarily in the inner lining, muscle layer, or the surrounding pericardium of the heart. They can be primary or metastatic. Primary cardiac tumours are rare in paediatric practice with a prevalence of 0.0017 to 0.28 in autopsy series. In contrast, the incidence of cardiac tumours during foetal life has been reported to be approximately 0.14%. The vast majority of primary cardiac tumours in children are benign, whilst approximately 10% are malignant. Secondary malignant tumours are 10–20 times more prevalent than primary malignant tumours. Rhabdomyoma is the most common cardiac tumour during foetal life and childhood. It accounts for more than 60% of all primary cardiac tumours. The frequency and type of cardiac tumours in adults differ from those in children with 75% being benign and 25% being malignant. Myxomas are the most common primary tumours in adults constituting 40% of benign tumours. Sarcomas make up 75% of malignant cardiac masses. Echocardiography, Computing Tomography (CT and Magnetic Resonance Imaging (MRI of the heart are the main non-invasive diagnostic tools. Cardiac catheterisation is seldom necessary. Tumour biopsy with histological assessment remains the gold standard for confirmation of the diagnosis. Surgical resection of primary cardiac tumours should be considered to relieve symptoms and mechanical obstruction to blood flow. The outcome of surgical resection in symptomatic, non-myxomatous benign cardiac tumours is favourable. Patients with primary cardiac malignancies may benefit from palliative surgery but this approach should not be recommended for patients with metastatic cardiac tumours. Surgery, chemotherapy and radiotherapy may prolong survival. The prognosis for malignant primary cardiac tumours is generally extremely poor.

  19. Percutaneous biopsy of non-palpable breast lesions with the advanced breast biopsy instrumentation (ABBI): analysis of indication strategies

    International Nuclear Information System (INIS)

    Purpose: To compare the indications for biopsy with and without the use of the Breast Imaging Reporting and Data System. Material and methods: Biopsies using the ABBI were performed in 62 patients with 64 non-palpable evident mammographic lesions. The initial decision for biopsy was made by non-radiologists due to suspicious microcalcifications (n=53) and masses (n=11). The indication was retrospectively reassessed by adopting the BI-RADS classification by three radiologists in consensus. The positive predictive value (PPV) of both indication strategies was assessed and compared. Results: Biopsies adopting ABBI were performed without major side-effects and were diagnostic. Carcinoma was present in 14 lesions: nine specimens were diagnosed as DCIS and five as invasive carcinomas. For the 50 benign lesions histology revealed mastopathies (26/50) and fibroadenomas (8/50) as the most frequent diagnosis. The positive predictive value (PPV) for the initial indication was 22%, whereas PPV for BI-RADS based indications (categories 4 and 5) was 31%. Conclusion: ABBI enables stereotactically-guided procedures that result in representative and diagnostic biopsies. Standardized criteria like BI-RADS improve the PPV and should be a mandatory part of mammographic evaluation. Radiologists should remain involved in the decision making. (orig.)

  20. Improving tumour response

    International Nuclear Information System (INIS)

    Radiation oncology is in the middle of the most exciting developments in its 100-year history. Progress in treatment planning and delivery, in medical imaging and in basic cancer and normal tissue biology is likely to change the indication for radiotherapy as well as the way it is prescribed and delivered. Technological and conceptual advances, in particular the development of the multi-leaf collimator and the concept of inverse treatment planning, have led to the introduction of intensity modulated radiation therapy (IMRT) with its capability to plan and deliver non-uniform dose distributions in the clinic. This has forced us to re-think radiation oncology: refining the indication for radiotherapy, optimizing the prescription of dose distributions and considering how, based on clinical evidence, radiation can best be combined with other treatment modalities, surgery, cytotoxic chemotherapy and biologically targeted therapies. The attraction of radiation therapy as an element of multi-modality cancer therapy is that it induces DNA damage that can be modulated in space and time. Progress in basic cancer biology, genomics and proteomics, as well as biological imaging provides novel avenues for individualization of cancer therapy and for biological optimization of radiotherapy. In improving cancer care, it is the therapeutic ratio, rather than tumour control per se, that must be optimised. Interestingly, the two main avenues for improving the effectiveness of radiotherapy currently being actively pursued in the clinic generally aim at different sides of the therapeutic ratio: 3D conformal radiotherapy and IMRT predominantly aim to reduce normal-tissue side effects - and by doing this, open the way for dose escalation that may lead to increased tumour control rates - whereas combined radio-chemotherapy aims to improve tumour response - while keeping the fingers crossed that this will not increase normal-tissue complications to the same extent. In parallel with these

  1. Introducing DeBRa: a detailed breast model for radiological studies

    Science.gov (United States)

    Ma, Andy K. W.; Gunn, Spencer; Darambara, Dimitra G.

    2009-07-01

    Currently, x-ray mammography is the method of choice in breast cancer screening programmes. As the mammography technology moves from 2D imaging modalities to 3D, conventional computational phantoms do not have sufficient detail to support the studies of these advanced imaging systems. Studies of these 3D imaging systems call for a realistic and sophisticated computational model of the breast. DeBRa (Detailed Breast model for Radiological studies) is the most advanced, detailed, 3D computational model of the breast developed recently for breast imaging studies. A DeBRa phantom can be constructed to model a compressed breast, as in film/screen, digital mammography and digital breast tomosynthesis studies, or a non-compressed breast as in positron emission mammography and breast CT studies. Both the cranial-caudal and mediolateral oblique views can be modelled. The anatomical details inside the phantom include the lactiferous duct system, the Cooper ligaments and the pectoral muscle. The fibroglandular tissues are also modelled realistically. In addition, abnormalities such as microcalcifications, irregular tumours and spiculated tumours are inserted into the phantom. Existing sophisticated breast models require specialized simulation codes. Unlike its predecessors, DeBRa has elemental compositions and densities incorporated into its voxels including those of the explicitly modelled anatomical structures and the noise-like fibroglandular tissues. The voxel dimensions are specified as needed by any study and the microcalcifications are embedded into the voxels so that the microcalcification sizes are not limited by the voxel dimensions. Therefore, DeBRa works with general-purpose Monte Carlo codes. Furthermore, general-purpose Monte Carlo codes allow different types of imaging modalities and detector characteristics to be simulated with ease. DeBRa is a versatile and multipurpose model specifically designed for both x-ray and γ-ray imaging studies.

  2. Introducing DeBRa: a detailed breast model for radiological studies

    Energy Technology Data Exchange (ETDEWEB)

    Ma, Andy K W; Darambara, Dimitra G [Joint Department of Physics, Institute of Cancer Research and Royal Marsden NHS Foundation Trust, Fulham Road, London SW3 6JJ (United Kingdom); Gunn, Spencer [Dexela Ltd, Wenlock Business Centre, 50/52 Wharf Road, London N1 7SF (United Kingdom)], E-mail: andyma@physics.org, E-mail: dimitra.darambara@icr.ac.uk, E-mail: spencer@dexelaimaging.com

    2009-07-21

    Currently, x-ray mammography is the method of choice in breast cancer screening programmes. As the mammography technology moves from 2D imaging modalities to 3D, conventional computational phantoms do not have sufficient detail to support the studies of these advanced imaging systems. Studies of these 3D imaging systems call for a realistic and sophisticated computational model of the breast. DeBRa (Detailed Breast model for Radiological studies) is the most advanced, detailed, 3D computational model of the breast developed recently for breast imaging studies. A DeBRa phantom can be constructed to model a compressed breast, as in film/screen, digital mammography and digital breast tomosynthesis studies, or a non-compressed breast as in positron emission mammography and breast CT studies. Both the cranial-caudal and mediolateral oblique views can be modelled. The anatomical details inside the phantom include the lactiferous duct system, the Cooper ligaments and the pectoral muscle. The fibroglandular tissues are also modelled realistically. In addition, abnormalities such as microcalcifications, irregular tumours and spiculated tumours are inserted into the phantom. Existing sophisticated breast models require specialized simulation codes. Unlike its predecessors, DeBRa has elemental compositions and densities incorporated into its voxels including those of the explicitly modelled anatomical structures and the noise-like fibroglandular tissues. The voxel dimensions are specified as needed by any study and the microcalcifications are embedded into the voxels so that the microcalcification sizes are not limited by the voxel dimensions. Therefore, DeBRa works with general-purpose Monte Carlo codes. Furthermore, general-purpose Monte Carlo codes allow different types of imaging modalities and detector characteristics to be simulated with ease. DeBRa is a versatile and multipurpose model specifically designed for both x-ray and {gamma}-ray imaging studies.

  3. Advances in the management of metastatic non-seminomatous germ cell tumours during the cisplatin era: a single-institution experience.

    OpenAIRE

    Gerl, A; Clemm, C.; Schmeller, N.; Hartenstein, R.; Lamerz, R.; Wilmanns, W.

    1996-01-01

    Long-term outcome was reviewed in 266 consecutive patients with metastatic non-seminomatous germ cell tumours treated at a single institution. The overall 3 year survival was 77%, and 3 year progression-free survival was 71%. Multivariate analysis identified the following clinical features as independent prognostic factors: the presence of liver, bone or brain metastasis, serum human chorionic gonadotropin > or = 10000 U l-1 and/or alpha-fetoprotein > or = 1000 ng ml-1, a mediastinal mass > 5...

  4. Breast cancer seeking agents: Basic approach

    International Nuclear Information System (INIS)

    The knowledge of biochemical and physiological mechanisms involved in tissue localization is important so as to understand the information given by diagnostic nuclear medicine imaging, and eventually to design new radiopharmaceuticals. The cellular mechanisms which permit a high cancer uptake involve the perfusion and metabolism within the tumour. All these phenomena can contribute to a high concentration of particular radiotracers in cancer and can create a favourable tumour/background ratio uptake sufficient for cancer imaging. Those molecules might be also powerful tools for reaching and advanced understanding of neoplastic and even ''normal'' cell biology. During these last years, some radiotracer specifically designed for different applications proved to be promising radiopharmaceuticals for breast cancer imaging. This is the case of monoclonal antibodies (Mabs) developed in the past against membrane cancer antigens. Other tracers, originally proposed for the study of vascular perfusion have also revealed a capacity to be taken up by cancer cells. The radiopharmaceuticals mostly used as tumour seeking agents today (Radiothallium, Sestamibi, Tetrophosmin) were generated with other applications in mind. In this paper whey review the mechanisms of uptake of the most relevant agents currently proposed for breast cancer imaging, including 18F-fluorodeoxyglucose (FDG). The radiotracers will be examined on the basis of the available scientific evidence regarding their cellular uptake and release. Moreover, they report their preliminary studies on the cellular uptake and release of these and other compounds recently introduced in clinical trials

  5. Carboplatin and Paclitaxel Albumin-Stabilized Nanoparticle Formulation Before Surgery in Treating Patients With Locally Advanced or Inflammatory Triple Negative Breast Cancer

    Science.gov (United States)

    2016-07-14

    Inflammatory Breast Cancer; Stage IIA Breast Cancer; Stage IIIA Breast Cancer; Stage IIIB Breast Cancer; Stage IIIC Breast Cancer; Triple-negative Breast Cancer; Stage IIB Breast Cancer; Estrogen Receptor Negative; Progesterone Receptor Negative; HER2/Neu Negative

  6. Brain tumour stem cells: the undercurrents of human brain cancer and their relationship to neural stem cells

    OpenAIRE

    Dirks, Peter B.

    2007-01-01

    Conceptual and technical advances in neural stem cell biology are being applied to the study of human brain tumours. These studies suggest that human brain tumours are organized as a hierarchy and are maintained by a small number of tumour cells that have stem cell properties. Most of the bulk population of human brain tumours comprise cells that have lost the ability to initiate and maintain tumour growth. Although the cell of origin for human brain tumours is uncertain, recent evidence poin...

  7. Recruitment and Early Retention of Women with Advanced Breast Cancer in a Complementary and Alternative Medicine Trial

    Directory of Open Access Journals (Sweden)

    Alla Sikorskii

    2011-01-01

    Full Text Available More than 80% of women with breast cancer are now reported to be using complementary and alternative medicine (CAM therapies during conventional treatment. A randomized clinical trial (RCT of reflexology with late stage breast cancer patients serves as the data source for this article. The purposes were to investigate: (i reasons for refusal to participate in a RCT of reflexology; (ii the differences between those who completed the baseline interview and those who dropped out before baseline; and (iii the utility of the Palliative Prognostic Score (PPS as a prognostic screening tool in minimizing early attrition (before baseline from the trial. Eligible women (N = 400 approached at 12 cancer centers in the Midwest had advanced breast cancer, were on chemotherapy or hormonal therapy, and had a PPS of 11 or less. Comparisons of those who dropped out early (N = 33 to those who stayed in the trial (N = 240 were carried out using Wilcoxon rank, t-, chi-squared and Fisher's exact tests. The reasons of being “too sick” or “overwhelmed” were given by less than 12% of the women who refused to participate. There was a higher early dropout rate among black women compared to other (primarily white women (P = .01. Cancer recurrence and metastasis, age, and the PPS were not predictive of early retention of women. Specialized techniques may be needed to ensure black women remain in the trial once consented. Women with advanced disease were likely to enter and remain in the trial despite deterioration in health.

  8. Advances in breast cancer screening program%乳腺癌筛查研究进展

    Institute of Scientific and Technical Information of China (English)

    莫淼; 柳光宇; 吕力琅; 徐望红

    2012-01-01

    Breast cancer is the most common malignancy in women around the world. Breast cancer screening has been recognized as the primary approach to effectively improve the survival of female breast cancer. The most commonly used methods for breast cancer screening in China and other countries include mammography (MAM), ultrasonography (US), clinical breast examination (CBE) and magnetic resonance imaging (MRI). This paper summarizes the advantages and disadvantages of these screening techniques and reviewes the economic efficiency in health care of different screening techniques based on these examination approaches to provide some evidence for developing a breast cancer screening strategy with optimal cost-effectiveness for Chinese women.%乳腺癌是危害全世界女性健康最常见的恶性肿瘤.乳腺癌筛查是公认的能够有效提高女性乳腺癌生存率的主要方法.目前国内外常用的乳腺癌筛查手段包括乳房X线摄影术(钼靶X线摄影)、超声成像、临床乳腺检查和磁共振成像等.本文对这些筛查手段的优缺点进行了比较,并对基于这些手段建立的不同筛查方案在人群中的应用效果和卫生经济学评价进行综述,以期为建立符合中国国情的具有成本-效果的女性乳腺癌筛查策略提供参考和依据.

  9. Tolerability of Therapies Recommended for the Treatment of Hormone Receptor-Positive Locally Advanced or Metastatic Breast Cancer.

    Science.gov (United States)

    Ohno, Shinji

    2016-08-01

    For women with hormone receptor-positive advanced breast cancer, endocrine therapies, including the selective estrogen receptor modulator tamoxifen, the aromatase inhibitors anastrozole, letrozole, and exemestane, and the selective estrogen receptor degrader fulvestrant, are recommended in clinical guidelines. The addition of targeted agents such as everolimus or palbociclib to aromatase inhibitors are also recommended as treatment options. Chemotherapy remains an option, although clinical guidelines have recommended these agents be reserved for patients with immediately life-threatening disease or if resistance to endocrine therapy is known or suspected. The present review has consolidated the tolerability profiles of the agents approved for use in the treatment of hormone receptor-positive advanced or metastatic breast cancer based on phase III registration trial data. Endocrine therapies are generally well tolerated, although the addition of targeted therapies to aromatase inhibitors or fulvestrant appears to increase the proportion of patients experiencing adverse events, and palbociclib and chemotherapy appear to be more closely associated with serious adverse events, including neutropenia. PMID:27151773

  10. Advances in the knowledge of breast cancer stem cells. A review.

    Science.gov (United States)

    Schwarz-Cruz Y Celis, Angela; Espinosa, Magali; Maldonado, Vilma; Melendez-Zajgla, Jorge

    2016-06-01

    Much effort has been made by researchers to elucidate the complex biology of breast cancer stem cells (BCSCs), a small subset of breast tumor cells that display stem cell properties, drive tumor initiation, and growth. In recent years, it has been suggested that BCSCs could be responsible for the process of metastasis and the development of drug resistance. These findings make the need to find the distinguishing blend of markers that can recognize only BCSCs of the utmost importance in order to be able to design new targeted therapies. This review will summarize BCSCs' main features as well as the cell surface markers that are currently used to identify them. PMID:26715540

  11. Pre-therapeutic dosimetry and biodistribution of 86Y-DOTA-Phe1-Tyr3-octreotide versus 111In-pentetreotide in patients with advanced neuroendocrine tumours

    International Nuclear Information System (INIS)

    For the internal radiotherapy of neuroendocrine tumours, the somatostatin analogue DOTATOC labelled with 90Y is frequently used [90Y-DOTA-Phe1-Tyr3-octreotide (SMT487-OctreoTher)]. Radiation exposure to the kidneys is critical in this therapy as it may result in renal failure. The aim of this study was to compare cumulative organ and tumour doses based upon dosimetric data acquired with the chemically identical 86Y-DOTA-Phe1-Tyr3-octreotide (considered as the gold standard) and the commercially available 111In-pentetreotide. The cumulative organ and tumour doses for the therapeutic administration of 13.32 GBq 90Y-DOTA-Phe1-Tyr3-octreotide (three cycles, each of 4.44 GBq) were estimated based on the MIRD concept (MIRDOSE 3.1 and IMEDOSE). Patients with a cumulative kidney dose exceeding 27 Gy had to be excluded from subsequent therapy with 90Y-DOTA-Phe1-Tyr3-octreotide, in accordance with the directives of the German radiation protection authorities. The range of doses (mGy/MBq 90Y-DOTA-Phe1-Tyr3-octreotide) for kidneys, spleen, liver and tumour masses was 0.6-2.8, 1.5-4.2, 0.3-1.3 and 2.1-29.5 (86Y-DOTA-Phe1-Tyr3-octreotide), respectively, versus 1.3-3.0, 1.8-4.4, 0.2-0.8 and 1.4-19.7 (111In-pentetreotide), with wide inter-subject variability. Despite renal protection with amino acid infusions, estimated cumulative kidney doses in two patients exceeded 27 Gy. Compared with 86Y-DOTA-Phe1-Tyr3-octreotide, dosimetry with 111In-pentetreotide overestimated doses to kidneys and spleen, whereas the radiation dose to the tumour-free liver was underestimated. However, both dosimetric approaches detected the two patients with an exceptionally high radiation burden to the kidneys that carried a potential risk of renal failure following radionuclide therapy. (orig.)

  12. Juvenile granulosa cell tumour: a rare clinical entity

    Directory of Open Access Journals (Sweden)

    Kaliki Hymavathi Reddy

    2014-08-01

    Full Text Available Ovarian cancer is the third most common neoplasm of the female genital tract. Based on the cell type of origin, primary ovarian malignancies are classified into surface epithelium, germ cell, and sex cord tumors. Sex cord tumors account for 1% to 2% of ovarian malignancies. They may contain granulosa cells, theca cells, sertoli cells, or fibroblasts of gonadal stromal origin. Granulosa Cell Tumours (GCTs account for approximately 2-5% of all ovarian tumors and can be divided into adult (95% and juvenile (5% types based on histologic findings. GCTs secrete estrogen thus resulting in menstrual irregularities in the affected individual. More serious estrogen effects can occur in various end organs such as uterus resulting in endometrial hyperplasia, endometrial adenocarcinomas and increased risk of breast cancers. Androgen production is also reported but rare and produces virilization in the affected women. Juvenile Granulosa Cell Tumours (JGCTs are clinically and histopathologically distinct from the GCTs. They are rarely encountered but mostly in youngsters. Surgery is the primary modality of treatment with chemotherapy being reserved for advanced or recurrent disease states. We herewith report an interesting case of JGCT in a young teenage girl. [Int J Reprod Contracept Obstet Gynecol 2014; 3(4.000: 1150-1154

  13. The synthesis of 16α-[131I]iodo-oestradiol and evaluation of its use as a radiotracer for oestrogen receptor positive breast tumours

    International Nuclear Information System (INIS)

    16α-Iodo-oestradiol binds with high affinity to the oestrogen receptor and has been shown to accumulate in oestrogen sensitive tissues in many test systems. The authors have prepared the compound labelled with 131I at four specific activities. Using these preparations we have attempted to image human primary and metastatic breast cancer deposits at various times from 15 min to 24 h post injection by external gamma scintigraphy. Clinical studies were conducted on 10 post-menopausal patients. The receptor status was determined in seven cases, four were positive and three negative. The imaging results were very poor, in only two cases were images obtained, these were very faint and only of the primary, never of the metastatic deposits. The oestrogen receptor status was only available in one of these cases; it was positive. Dynamic studies in vivo revealed that the compound is cleared rapidly from the circulation during the first 5 min and thereafter undergoes extensive enterohepatic recycling. Studies of the radiochemical identity of the circulating species revealed that the injected compound was extensively metabolised. Neither an increase in specific activity of injected radiotracer nor imaging at shorter times after injection improved the results. (author)

  14. Profiling post translational modification of histone and p53 in human breast carcinomas

    OpenAIRE

    Abdelghany, Magdy Korashy

    2011-01-01

    Breast cancer is one of the most common cancers in females in the western world, and despite the advances in diagnosis and treatment it is still associated with significant morbidity. Thus, improvements to existing treatment modalities remain a priority. Understanding the molecular mechanisms controlling tumour growth and its modulation will be key to developing new therapies. In recent years it has been shown that posttranslational modifications (PTMs) of histones and p53 are functionally im...

  15. Advancing Social Workers' Responsiveness to Health Disparities: The Case of Breast Cancer Screening

    Science.gov (United States)

    Altpeter, Mary; Mitchell, James F.; Pennell, Joan

    2005-01-01

    This study provides the basis for customizing culturally responsive social work health promotion programs aimed at eliminating breast cancer screening and mortality disparities between white and African American women. Survey data collected from a random sample of 853 women in rural North Carolina were used to explore the impact of psychosocial…

  16. Heterogeneity of focal breast lesions and surrounding tissue assessed by mammographic texture analysis: Preliminary evidence of an association with tumour invasion and oestrogen receptor status

    Directory of Open Access Journals (Sweden)

    BalajiGaneshan

    2011-10-01

    Full Text Available Aim: This pilot study investigates the heterogeneity in focal breast lesions and surrounding tissue assessed on mammography is potentially related to cancer invasion and hormone receptor status. Materials and Methods: Texture analysis (TA assessed the heterogeneity of focal lesions and their surrounding tissues in digitised mammograms from 11 patients randomly selected from an imaging archive (Ductal Carcinoma in Situ (DCIS only, n=4; Invasive Carcinoma (IC with DCIS, n=3; IC only, n=4. TA utilised band-pass image filtration to highlight image features at different spatial frequencies (filter values: 1.0-2.5 from fine to coarse texture. The distribution of features in the derived images was quantified using uniformity. Results: Significant differences in uniformity were observed between patient groups for all filter values. With medium scale filtration (filter value = 1.5 pure DCIS was more uniform (median = 0.281 than either DCIS with IC (median = 0.246, p= 0.0102 or IC (median = 0.249, p= 0.0021. Lesions with high levels of oestrogen receptor expression were more uniform, most notably with coarse filtration (filter values 2.0 and 2.5, rs = 0.812, p = 0.002. Comparison of uniformity values in focal lesions and surrounding tissue showed significant differences between DCIS with or without IC versus IC (p=0.0009. Conclusion: This pilot study shows the potential for computer-based assessments of heterogeneity within focal mammographic lesions and surrounding tissue to identify adverse pathological features in mammographic lesions. The technique warrants further investigation as a possible adjunct to existing computer aided diagnosis systems.

  17. Learning from social media: utilizing advanced data extraction techniques to understand barriers to breast cancer treatment.

    Science.gov (United States)

    Freedman, Rachel A; Viswanath, Kasisomayajula; Vaz-Luis, Ines; Keating, Nancy L

    2016-07-01

    Past examinations of breast cancer treatment barriers have typically included registry, claims-based, and smaller survey studies. We examined treatment barriers using a novel, comprehensive, social media analysis of online, candid discussions about breast cancer. Using an innovative toolset to search postings on social networks, message boards, patient communities, and topical sites, we performed a large-scale qualitative analysis. We examined the sentiments and barriers expressed about breast cancer treatments by Internet users during 1 year (2/1/14-1/31/15). We categorized posts based on thematic patterns and examined trends in discussions by race/ethnicity (white/black/Hispanic) when this information was available. We identified 1,024,041 unique posts related to breast cancer treatment. Overall, 57 % of posts expressed negative sentiments. Using machine learning software, we assigned treatment barriers for 387,238 posts (38 %). Barriers included emotional (23 % of posts), preferences and spiritual/religious beliefs (21 %), physical (18 %), resource (15 %), healthcare perceptions (9 %), treatment processes/duration (7 %), and relationships (7 %). Black and Hispanic (vs. white) users more frequently reported barriers related to healthcare perceptions, beliefs, and pre-diagnosis/diagnosis organizational challenges and fewer emotional barriers. Using a novel analysis of diverse social media users, we observed numerous breast cancer treatment barriers that differed by race/ethnicity. Social media is a powerful tool, allowing use of real-world data for qualitative research, capitalizing on the rich discussions occurring spontaneously online. Future research should focus on how to further employ and learn from this type of social intelligence research across all medical disciplines. PMID:27339067

  18. The use of complementary and alternative medicines among patients with locally advanced breast cancer – a descriptive study

    Directory of Open Access Journals (Sweden)

    Rakovitch Eileen

    2006-02-01

    Full Text Available Abstract Background Complementary and alternative medicine (CAM use is common among cancer patients. This paper reviews the use of CAM in a series of patients with locally advanced breast cancer (LABC. Methods Women with LABC attending a specialist clinic at a single Canadian cancer centre were identified and approached. Participants completed a self-administered survey regarding CAM usage, beliefs associated with CAM usage, views of their risks of developing recurrent cancer and of dying of breast cancer. Responses were scored and compared between CAM users and non-users. Results Thirty-six patients were approached, 32 completed the questionnaire (response rate 89%. Forty-seven percent of LABC patients were identified as CAM users. CAM users were more likely to be younger, married, in a higher socioeconomic class and of Asian ethnicity than non-users. CAM users were likely to use multiple modalities simultaneously (median 4 with vitamins being the most popular (60%. Motivation for CAM therapy was described as, "assisting their body to heal" (75%, to 'boost the immune system' (56% and to "give a feeling of control with respect to their treatment" (56%. CAM therapy was used concurrently with conventional treatment in 88% of cases, however, 12% of patients felt that CAM could replace their conventional therapy. Psychological evaluation suggests CAM users perceived their risk of dying of breast cancer was similar to that of the non-Cam group (33% vs. 35%, however the CAM group had less severe anxiety and depression. Conclusion The motivation, objectives and benefits of CAM therapy in a selected population of women with LABC are similar to those reported for women diagnosed with early stage breast cancer. CAM users display less anxiety and depression and are less likely to believe they will die of their breast cancer. However the actual benefit to overall and disease free survival has yet to be demonstrated, as well as the possible interactions with

  19. 18F-FLT PET/CT as an imaging tool for early prediction of pathological response in patients with locally advanced breast cancer treated with neoadjuvant chemotherapy: a pilot study

    International Nuclear Information System (INIS)

    We evaluated whether 18F-3'-deoxy-3'-fluorothymidine positron emission tomography (FLT PET) can predict the final postoperative histopathological response in primary breast cancer after the first cycle of neoadjuvant chemotherapy (NCT). In this prospective cohort study of 15 patients with locally advanced operable breast cancer, FLT PET evaluations were performed before NCT, after the first cycle of NCT, and at the end of NCT. All patients subsequently underwent surgery. Variables from FLT PET examinations were correlated with postoperative histopathological results. At baseline, median of maximum standardized uptake values (SUVmax) in the groups showing a complete pathological response (pCR) + residual cancer burden (RCB) I, RCB II or RCB III did not differ significantly for the primary tumour (5.0 vs. 2.9 vs. 8.9, p = 0.293) or for axillary nodes (7.9 vs. 1.6 vs. 7.0, p = 0.363), whereas the Spearman correlation between SUVmax and Ki67 proliferation rate index was significant (r = 0.69, p < 0.001). Analysis of the relative percentage change of SUVmaxin the primary tumour (∇SUVTmax(t1)) and axillary nodes (∇SUVNmax(t1)) after the first NCT cycle showed that the power of ∇SUVTmax(t1) to predict pCR + RCB I responses (AUC = 0.91, p < 0.001) was statistically significant, whereas ∇SUVNmax(t1) had a moderate ability (AUC = 0.77, p = 0.119) to separate subjects with ΔSUVTmax(t1) > -52.9 % into two groups: RCB III patients and a heterogeneous group that included RCB I and RCB II patients. A predictive score μ based on ΔSUVTmax(t1) and ΔSUVNmax(t1) parameters is proposed. The preliminary findings of the present study suggest the potential utility of FLT PET scans for early monitoring of response to NCT and to formulate a therapeutic strategy consistent with the estimated efficacy of NCT. However, these results in a small patient population need to be validated in a larger independent cohort. (orig.)

  20. {sup 18}F-FLT PET/CT as an imaging tool for early prediction of pathological response in patients with locally advanced breast cancer treated with neoadjuvant chemotherapy: a pilot study

    Energy Technology Data Exchange (ETDEWEB)

    Crippa, Flavio; Padovano, Barbara; Alessi, Alessandra; Bombardieri, Emilio; Pascali, Claudio; Bogni, Anna [Fondazione IRCCS Istituto Nazionale dei Tumori, Milan (Italy). Nuclear Medicine Unit; Agresti, Roberto; Maugeri, Ilaria; Rampa, Mario; Martelli, Gabriele [Fondazione IRCCS Istituto Nazionale dei Tumori, Milan (Italy). Breast Surgery Unit; Sandri, Marco [Fondazione IRCCS Istituto Nazionale dei Tumori, Milan (Italy). Molecular Targeting Unit; Mariani, Gabriella; Bianchi, Giulia; De Braud, Filippo [Fondazione IRCCS Istituto Nazionale dei Tumori, Milan (Italy). Medical Oncology Unit; Carcangiu, Maria Luisa [Fondazione IRCCS Istituto Nazionale dei Tumori, Milan (Italy). Pathology Unit; Trecate, Giovanna [Fondazione IRCCS Istituto Nazionale dei Tumori, Milan (Italy). Radiology-RMI Unit

    2015-05-01

    We evaluated whether {sup 18}F-3'-deoxy-3'-fluorothymidine positron emission tomography (FLT PET) can predict the final postoperative histopathological response in primary breast cancer after the first cycle of neoadjuvant chemotherapy (NCT). In this prospective cohort study of 15 patients with locally advanced operable breast cancer, FLT PET evaluations were performed before NCT, after the first cycle of NCT, and at the end of NCT. All patients subsequently underwent surgery. Variables from FLT PET examinations were correlated with postoperative histopathological results. At baseline, median of maximum standardized uptake values (SUV{sub max}) in the groups showing a complete pathological response (pCR) + residual cancer burden (RCB) I, RCB II or RCB III did not differ significantly for the primary tumour (5.0 vs. 2.9 vs. 8.9, p = 0.293) or for axillary nodes (7.9 vs. 1.6 vs. 7.0, p = 0.363), whereas the Spearman correlation between SUV{sub max} and Ki67 proliferation rate index was significant (r = 0.69, p < 0.001). Analysis of the relative percentage change of SUV{sub max}in the primary tumour (∇SUVT{sub max}(t{sub 1})) and axillary nodes (∇SUVN{sub max}(t{sub 1})) after the first NCT cycle showed that the power of ∇SUVT{sub max}(t{sub 1}) to predict pCR + RCB I responses (AUC = 0.91, p < 0.001) was statistically significant, whereas ∇SUVN{sub max}(t{sub 1}) had a moderate ability (AUC = 0.77, p = 0.119) to separate subjects with ΔSUVT{sub max}(t{sub 1}) > -52.9 % into two groups: RCB III patients and a heterogeneous group that included RCB I and RCB II patients. A predictive score μ based on ΔSUVT{sub max}(t{sub 1}) and ΔSUVN{sub max}(t{sub 1}) parameters is proposed. The preliminary findings of the present study suggest the potential utility of FLT PET scans for early monitoring of response to NCT and to formulate a therapeutic strategy consistent with the estimated efficacy of NCT. However, these results in a small patient population

  1. Tumours and tumour mimics in the olecranon

    International Nuclear Information System (INIS)

    Lesions in the olecranon are rare and may be identified during the investigation of a clinically suspected abnormality or as an incidental finding. This review describes the spectrum of tumours and tumour-like lesions that can involve the olecranon and illustrates the radiographic, CT, and MRI appearances that may facilitate diagnosis. A variety of pathological processes affecting the olecranon are presented and discussed including the epidemiology and imaging features

  2. Neuroendocrine breast cancer

    OpenAIRE

    Graça, Susana; Esteves, Joana; Costa, Sílvia; Vale, Sílvio; Maciel, Jorge

    2012-01-01

    Neuroendocrine breast cancer is thought to account for about 1% of all breast cancers. This rare type of breast malignancy is more common in older women and presents as a low-grade, slow-growing cancer. The most definitive markers that indicate neuroendocrine carcinoma are the presence of chromogranin, synaptophysin or neuron-specific enolase, in at least 50% of malignant tumour cells. The authors present a case report of an 83-year-old woman, admitted to their institution with right breast l...

  3. Locally advanced breast implant-associated anaplastic large-cell lymphoma: a case report of successful treatment with radiation and chemotherapy.

    Science.gov (United States)

    Estes, Christopher F; Zhang, Da; Reyes, Ruben; Korentager, Richard; McGinness, Marilee; Lominska, Christopher

    2015-01-01

    The development of breast implant-associated anaplastic large-cell lymphoma (ALCL) is a rare phenomenon. A typical presentation is an effusion associated with a breast implant. Less commonly, disease can be more advanced locoregionally or distantly. The optimal treatment schema is a topic of debate: localized ALCL can potentially be cured with implant removal alone, while other cases in the literature, including those that are more advanced, have been treated with varying combinations of surgery, chemotherapy, and external beam radiotherapy. This is a case report of breast implant ALCL with pathologically proven lymph node involvement, the fifth such patient reported. Our patient experienced a favorable outcome with radiation therapy and chemotherapy. PMID:25741471

  4. Concordance of Hypermethylated DNA and the Tumor Markers CA 15-3, CEA, and TPA in Serum during Monitoring of Patients with Advanced Breast Cancer

    DEFF Research Database (Denmark)

    Kristiansen, Søren; Jørgensen, Lars Mønster; Høgh Hansen, Morten;

    2015-01-01

    The serological protein tumor markers CA 15-3, CEA, and TPA are frequently used to monitor tumor burden among metastatic breast cancer patients. Breast cancer is associated with global DNA hypomethylation and hypermethylation of some promoter regions. No monitoring study has yet investigated the...... interrelationship between protein tumor markers, the global DNA hypomethylation, and hypermethylated genes in serum from patients with advanced disease. Twenty-nine patients with histologically proven advanced breast cancer received first-line chemotherapy with epirubicin. Samples were collected prior to each...... treatment and prospectively analyzed for CA 15-3, CEA, and TPA. The same samples were retrospectively analyzed for the concentration of hypermethylated RASSF1A and for global DNA hypomethylation using LINE-1. Among patients with elevated concentrations of the protein markers, concordance could be observed...

  5. Comparison of prone versus supine 18F-FDG-PET of locally advanced breast cancer: Phantom and preliminary clinical studies

    Energy Technology Data Exchange (ETDEWEB)

    Williams, Jason M.; Rani, Sudheer D.; Li, Xia; Whisenant, Jennifer G.; Abramson, Richard G. [Institute of Imaging Science, Vanderbilt University, Nashville, Tennessee 37232 and Department of Radiology and Radiological Sciences, Vanderbilt University, Nashville, Tennessee 37232 (United States); Arlinghaus, Lori R. [Institute of Imaging Science, Vanderbilt University, Nashville, Tennessee 37232 (United States); Lee, Tzu-Cheng [Department of Bioengineering, University of Washington, Seattle, Washington 98195 (United States); MacDonald, Lawrence R.; Partridge, Savannah C. [Department of Radiology, University of Washington, Seattle, Washington 98195 (United States); Kang, Hakmook [Institute of Imaging Science, Vanderbilt University, Nashville, Tennessee 37232 and Department of Biostatistics, Vanderbilt University, Nashville, Tennessee 37232 (United States); Linden, Hannah M. [Department of Medical Oncology, University of Washington, Seattle, Washington 98195 (United States); Kinahan, Paul E. [Department of Radiology, University of Washington, Seattle, Washington 98195 (United States); Department of Bioengineering, University of Washington, Seattle, Washington 98195 (United States); Department of Physics, University of Washington, Seattle, Washington 98195 (United States); Department of Electrical Engineering, University of Washington, Seattle, Washington 98195 (United States); Yankeelov, Thomas E., E-mail: thomas.yankeelov@vanderbilt.edu [Institute of Imaging Science, Vanderbilt University, Nashville, Tennessee 37232 (United States); Department of Radiology and Radiological Sciences, Vanderbilt University, Nashville, Tennessee 37232 (United States); Department of Biomedical Engineering, Vanderbilt University, Nashville, Tennessee 37232 (United States); Department of Physics, Vanderbilt University, Nashville, Tennessee 37232 (United States); Department of Cancer Biology, Vanderbilt University, Nashville, Tennessee 37232 (United States)

    2015-07-15

    Purpose: Previous studies have demonstrated how imaging of the breast with patients lying prone using a supportive positioning device markedly facilitates longitudinal and/or multimodal image registration. In this contribution, the authors’ primary objective was to determine if there are differences in the standardized uptake value (SUV) derived from [{sup 18}F]fluorodeoxyglucose (18F-FDG) positron emission tomography (PET) in breast tumors imaged in the standard supine position and in the prone position using a specialized positioning device. Methods: A custom positioning device was constructed to allow for breast scanning in the prone position. Rigid and nonrigid phantom studies evaluated differences in prone and supine PET. Clinical studies comprised 18F-FDG-PET of 34 patients with locally advanced breast cancer imaged in the prone position (with the custom support) followed by imaging in the supine position (without the support). Mean and maximum values (SUV{sub peak} and SUV{sub max}, respectively) were obtained from tumor regions-of-interest for both positions. Prone and supine SUV were linearly corrected to account for the differences in 18F-FDG uptake time. Correlation, Bland–Altman, and nonparametric analyses were performed on uptake time-corrected and uncorrected data. Results: SUV from the rigid PET breast phantom imaged in the prone position with the support device was 1.9% lower than without the support device. In the nonrigid PET breast phantom, prone SUV with the support device was 5.0% lower than supine SUV without the support device. In patients, the median (range) difference in uptake time between prone and supine scans was 16.4 min (13.4–30.9 min), which was significantly—but not completely—reduced by the linear correction method. SUV{sub peak} and SUV{sub max} from prone versus supine scans were highly correlated, with concordance correlation coefficients of 0.91 and 0.90, respectively. Prone SUV{sub peak} and SUV{sub max} were

  6. Full dose paclitaxel plus vinorelbine as salvage chemotherapy in anthracycline-resistant advanced breast cancer: a phase II study.

    Science.gov (United States)

    Polyzos, A; Tsavaris, N; Kosmas, C; Gogas, H; Toufexi, H; Kosmidis, C; Markopoulos, C; Giannopoulos, A; Papadopoulos, O; Stamatiadis, D; Kouraklis, G

    2003-12-01

    This phase II trial studied the efficacy and toxicity of full dose paclitaxel plus vinorelbine, as salvage chemotherapy in patients with metastatic breast cancer resistant to anthracyclines. Patients received vinorelbine (30 mg/m2) followed 1 hour later by full dose paclitaxel (175 mg/m2) every 3 weeks for a maximum of 8 cycles or until disease progression. Because of the heavy pretreatment of the patients, prophylactic granulocyte-colony stimulating factor (5 microg/kg) was administered daily for 5-10 days. To minimize potentially cumulative neurotoxicity due to both agents, amifostine was given prior to chemotherapy. Thirty-four patients: 8 with tumors primary resistant and 26 with tumors recurring within 3-6 months after anthracycline treatment, were evaluable for efficacy and toxicity. Objective responses occurred in 11 patients [32%; 95% confidence interval (CI): 16.3-47.7%), all partial responses. Responses were observed in lung and liver. The median response duration was 4 months (range 3-7), median time to progression was 5 months (range 3-9) and median overall survival was 8 months (range 4-24). Neutropenia was dose limiting (35% grade 3-4 toxicity). The left ventricular ejection fraction, measured and followed in 18 patients, fell less than 20% below baseline level in 9 patients (50%), but only one patient developed congestive cardiac failure. The paclitaxel-vinorelbine regimen was moderately tolerated and moderately effective in poor prognosis breast cancer patients with visceral metastases and tumors resistant to anthracyclines. The combination at these doses and schedules should be considered in the design of regimens for advanced breast cancer. PMID:14998089

  7. [177Lu-DOTA]0-D-Phe1-Tyr3-Octreotide (177Lu-DOTATOC) For Peptide Receptor Radiotherapy in Patients with Advanced Neuroendocrine Tumours: A Phase-II Study

    Science.gov (United States)

    Baum, Richard P.; Kluge, Andreas W.; Kulkarni, Harshad; Schorr-Neufing, Ulrike; Niepsch, Karin; Bitterlich, Norman; van Echteld, Cees J.A.

    2016-01-01

    Purpose: To characterise efficacy and safety of 177Lu-DOTATOC as agent for peptide receptor radiotherapy (PRRT) of advanced neuroendocrine tumours (NET). Patients and methods: Fifty-six subjects with metastasized and progressive NET (50% gastroenteral, 26.8% pancreatic, 23.2% other primary sites) treated consecutively with 177Lu-DOTATOC were analysed retrospectively. Subjects were administered 177Lu-DOTATOC (mean 2.1 cycles; range 1-4) as 7.0GBq (median) doses at three-monthly intervals. Efficacy was analysed using CT and/or MRI according to RECIST 1.1 criteria and results were stratified for the number of administered cycles and the primary tumour origin. Results: In the total NET population (A), median progression-free (PFS) and overall survival (OS) were 17.4 and 34.2 months, respectively, assessed in a follow-up time (mean ± SD) of 16.1 ± 12.4 months. In patients receiving more than one cycle, mean follow-up time was 22.4 ± 11.0 months for all NETs (B) and PFS was 32.0 months for all NETs (B), 34.5 months for GEP-NET (C), and 11.9 months for other NETs (D). Objective response rates (Complete/Partial Responses) were 33.9%, 40.6%, 54.2%, and 0% for A, B, C, and D groups, respectively, while disease control rates in the same were 66.1%, 93.8%, 100%, and 75%. Complete responses (16.1%, 18.8% and 25.0% for groups A, B and C) were high, 78% of which were maintained throughout the follow up. There were no serious adverse events. One case of self-limiting grade 3 myelotoxicity was reported. Although 20% of patients had mild renal insufficiency at baseline, there was no evidence of exacerbated or de novo renal toxicity after treatment. Conclusion: 177Lu-DOTATOC is a novel agent for PRRT with major potential to induce objective tumour responses and sustained disease control in progressive neuroendocrine tumours, even when administered in moderate activities. The observed safety profile suggests a particularly favourable therapeutic index, including in patients with

  8. Lapatinib in combination with capecitabine in the management of ErbB2-positive (HER2-positive advanced breast cancer

    Directory of Open Access Journals (Sweden)

    Bella Kaufman

    2008-03-01

    Full Text Available Bella Kaufman1, Steven Stein2, Michelle A Casey2, Beth O Newstat21Sackler Faculty of Medicine, Tel Aviv University, Tel Aviv, Israel; 2GlaxoSmithKline, Collegeville, PA, USAAbstract: Lapatinib is an oral, reversible, dual inhibitor of epidermal growth factor receptor ErbB1 (EGFR and human epidermal growth factor receptor type 2 ErbB2 (HER2. Results of a phase III study comparing lapatinib plus capecitabine with capecitabine alone in women with ErbB2-overexpressing advanced breast cancer previously treated with an anthracycline, a taxane, and trastuzumab were reported early based on superiority of the combination in prolonging time to tumor progression (TTP. An updated analysis in 399 women supports the earlier findings. In this updated analysis, TTP (hazard ratio [HR] 0.57 favored lapatinib plus capecitabine. Survival trended in favor of the combination. The incidence of cardiac events was numerically higher in the combination arm (5 cases in the combination arm, 2 cases in the monotherapy arm.Keywords: lapatinib, capecitabine, breast cancer, HER2

  9. Docetaxel, Carboplatin, Trastuzumab, and Pertuzumab With or Without Estrogen Deprivation in Treating Patients With Hormone Receptor-Positive, HER2-Positive Operable or Locally Advanced Breast Cancer

    Science.gov (United States)

    2016-09-08

    Estrogen Receptor Positive; HER2/Neu Positive; Progesterone Receptor Positive; Stage IB Breast Cancer; Stage IIA Breast Cancer; Stage IIB Breast Cancer; Stage IIIA Breast Cancer; Stage IIIB Breast Cancer; Stage IIIC Breast Cancer

  10. Intraoperative tumour detection using 111In-DTPA-D-Phe1-octreotide and a scintillation detector

    International Nuclear Information System (INIS)

    Intraoperative tumour detection has been used in many applications. The examined tumour forms have varied and different detector systems and radiopharmaceuticals have also been used. The aim of this study was to evaluate and compare the ability of an NaI(Tl) scintillation detector to detect primary tumours and metastases in patients with different endocrine tumour types (e.g. carcinoid tumours, endocrine pancreatic tumours and thyroid tumours) and in patients with breast carcinoma or benign thyroid lesions, on the basis of their somatostatin receptor expression after i.v. injection of 111In-DTPA-D-Phe1-octreotide. Thirty patients were injected with 111In-DTPA-D-Phe1-octreotide intravenously. Scintigraphic images were taken 1 day after injection of the radiopharmaceutical, and surgery was performed 1-7 days post injection. An NaI(Tl) scintillation detector was used for intraoperative tumour detection. Tissue samples were collected during surgery for determination of 111In activity concentration and histopathological examination. The scintigraphic images were positive in 29 out of 30 patients. Intraoperative tumour detection was successful in 43 of 66 collected biopsies: 10 out of 11 for carcinoid tumours, 7 out of 10 for medullary thyroid carcinoma (MTC) and 14 out of 22 for breast cancer. On the basis of our findings we conclude that intraoperative tumour detection with 111In-DTPA-D-Phe1-octreotide using this NaI(Tl) detector can be successful especially for carcinoid tumours and endocrine pancreatic tumours, due to the relatively high activity concentrations in these tumour types, but is less successful in other forms of thyroid cancer, including MTC, and breast cancer. For successful intraoperative detection, the detector characteristics are also very important, and further improvement of the detector systems is required to increase the sensitivity and specificity. (orig.)

  11. Next-Generation Entrepreneurs Ready to Advance Breast Cancer Research Innovations | Poster

    Science.gov (United States)

    By Michele Newton and Thomas Stackhouse, Contributing Writers, and Rosemarie Truman, Guest Writer Editor’s note: In May 2014, the Breast Cancer Start-Up Challenge was named one of six finalists in the HHS Innovates Award Competition. This award celebrates innovations developed by employees of the U.S. Department of Health and Human Services (HHS) to support the mission of HHS. In the final phase of the competition, the public will be invited to help select “The People’s Choice” winner; public voting takes place May 29 through June 6, 2014.

  12. Early Toxicity in Patients Treated With Postoperative Proton Therapy for Locally Advanced Breast Cancer

    International Nuclear Information System (INIS)

    Purpose: To report dosimetry and early toxicity data in breast cancer patients treated with postoperative proton radiation therapy. Methods and Materials: From March 2013 to April 2014, 30 patients with nonmetastatic breast cancer and no history of prior radiation were treated with proton therapy at a single proton center. Patient characteristics and dosimetry were obtained through chart review. Patients were seen weekly while on treatment, at 1 month after radiation therapy completion, and at 3- to 6-month intervals thereafter. Toxicity was scored using Common Terminology Criteria for Adverse Events version 4.0. Frequencies of toxicities were tabulated. Results: Median dose delivered was 50.4 Gy (relative biological equivalent [RBE]) in 5 weeks. Target volumes included the breast/chest wall and regional lymph nodes including the internal mammary lymph nodes (in 93%). No patients required a treatment break. Among patients with >3 months of follow-up (n=28), grade 2 dermatitis occurred in 20 patients (71.4%), with 8 (28.6%) experiencing moist desquamation. Grade 2 esophagitis occurred in 8 patients (28.6%). Grade 3 reconstructive complications occurred in 1 patient. The median planning target volume V95 was 96.43% (range, 79.39%-99.60%). The median mean heart dose was 0.88 Gy (RBE) [range, 0.01-3.20 Gy (RBE)] for all patients, and 1.00 Gy (RBE) among patients with left-sided tumors. The median V20 of the ipsilateral lung was 16.50% (range, 6.1%-30.3%). The median contralateral lung V5 was 0.34% (range, 0%-5.30%). The median maximal point dose to the esophagus was 45.65 Gy (RBE) [range, 0-65.4 Gy (RBE)]. The median contralateral breast mean dose was 0.29 Gy (RBE) [range, 0.03-3.50 Gy (RBE)]. Conclusions: Postoperative proton therapy is well tolerated, with acceptable rates of skin toxicity. Proton therapy favorably spares normal tissue without compromising target coverage. Further follow-up is necessary to assess for clinical outcomes and cardiopulmonary

  13. Early Toxicity in Patients Treated With Postoperative Proton Therapy for Locally Advanced Breast Cancer

    Energy Technology Data Exchange (ETDEWEB)

    Cuaron, John J. [Memorial Sloan-Kettering Cancer Center, New York, New York (United States); Chon, Brian; Tsai, Henry; Goenka, Anuj; DeBlois, David [Procure Proton Therapy Center, Somerset, New Jersey (United States); Ho, Alice; Powell, Simon [Memorial Sloan-Kettering Cancer Center, New York, New York (United States); Hug, Eugen [Procure Proton Therapy Center, Somerset, New Jersey (United States); Cahlon, Oren, E-mail: cahlono@mskcc.org [Memorial Sloan-Kettering Cancer Center, New York, New York (United States); Procure Proton Therapy Center, Somerset, New Jersey (United States)

    2015-06-01

    Purpose: To report dosimetry and early toxicity data in breast cancer patients treated with postoperative proton radiation therapy. Methods and Materials: From March 2013 to April 2014, 30 patients with nonmetastatic breast cancer and no history of prior radiation were treated with proton therapy at a single proton center. Patient characteristics and dosimetry were obtained through chart review. Patients were seen weekly while on treatment, at 1 month after radiation therapy completion, and at 3- to 6-month intervals thereafter. Toxicity was scored using Common Terminology Criteria for Adverse Events version 4.0. Frequencies of toxicities were tabulated. Results: Median dose delivered was 50.4 Gy (relative biological equivalent [RBE]) in 5 weeks. Target volumes included the breast/chest wall and regional lymph nodes including the internal mammary lymph nodes (in 93%). No patients required a treatment break. Among patients with >3 months of follow-up (n=28), grade 2 dermatitis occurred in 20 patients (71.4%), with 8 (28.6%) experiencing moist desquamation. Grade 2 esophagitis occurred in 8 patients (28.6%). Grade 3 reconstructive complications occurred in 1 patient. The median planning target volume V95 was 96.43% (range, 79.39%-99.60%). The median mean heart dose was 0.88 Gy (RBE) [range, 0.01-3.20 Gy (RBE)] for all patients, and 1.00 Gy (RBE) among patients with left-sided tumors. The median V20 of the ipsilateral lung was 16.50% (range, 6.1%-30.3%). The median contralateral lung V5 was 0.34% (range, 0%-5.30%). The median maximal point dose to the esophagus was 45.65 Gy (RBE) [range, 0-65.4 Gy (RBE)]. The median contralateral breast mean dose was 0.29 Gy (RBE) [range, 0.03-3.50 Gy (RBE)]. Conclusions: Postoperative proton therapy is well tolerated, with acceptable rates of skin toxicity. Proton therapy favorably spares normal tissue without compromising target coverage. Further follow-up is necessary to assess for clinical outcomes and cardiopulmonary

  14. Differential effects of garcinol and curcumin on histone and p53 modifications in tumour cells

    OpenAIRE

    Collins Hilary M; Abdelghany Magdy K; Messmer Marie; Yue Baigong; Deeves Sian E; Kindle Karin B; Mantelingu Kempegowda; Aslam Akhmed; Winkler G Sebastiaan; Kundu Tapas K; Heery David M

    2013-01-01

    Abstract Background Post-translational modifications (PTMs) of histones and other proteins are perturbed in tumours. For example, reduced levels of acetylated H4K16 and trimethylated H4K20 are associated with high tumour grade and poor survival in breast cancer. Drug-like molecules that can reprogram selected histone PTMs in tumour cells are therefore of interest as potential cancer chemopreventive agents. In this study we assessed the effects of the phytocompounds garcinol and curcumin on hi...

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

    DEFF Research Database (Denmark)

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

    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...

  16. Phase II trial of weekly nab-paclitaxel and carboplatin treatment with or without trastuzumab as nonanthracycline neoadjuvant chemotherapy for locally advanced breast cancer

    OpenAIRE

    Huang L; Chen S; Yao L; Liu GY; Wu J; Shao ZM

    2015-01-01

    Liang Huang,1,2 Sheng Chen,1,2 Ling Yao,1,2 Guangyu Liu,1,2 Jiong Wu,1,2 Zhiming Shao1–3 1Department of Breast Surgery, Fudan University Shanghai Cancer Center/Cancer Institute, 2Department of Oncology, Shanghai Medical College, 3Institutes of Biomedical Science, Fudan University, Shanghai, People’s Republic of China Background: Neoadjuvant chemotherapy has become standard treatment for women with locally advanced breast cancer. The aim of this study was to compare the...

  17. Changes in subcellular doxorubicin distribution and cellular accumulation alone can largely account for doxorubicin resistance in SW-1573 lung cancer and MCF-7 breast cancer multidrug resistant tumour cells.

    Science.gov (United States)

    Schuurhuis, G. J.; van Heijningen, T. H.; Cervantes, A.; Pinedo, H. M.; de Lange, J. H.; Keizer, H. G.; Broxterman, H. J.; Baak, J. P.; Lankelma, J.

    1993-01-01

    Doxorubicin accumulation defects in multidrug resistant tumour cells are generally small in comparison to the resistance factors. Therefore additional mechanisms must be operative. In this paper we show by a quantitative approach that doxorubicin resistance in several P-glycoprotein-positive non-small cell lung cancer and breast cancer multidrug resistant cell lines can be explained by a summation of accumulation defect and alterations in the efficacy of the drug once present in the cell. This alteration of efficacy was partly due to changes in intracellular drug localisation, characterised by decreased nuclear/cytoplasmic doxorubicin fluorescence ratios (N/C-ratios). N/C-ratios were 2.8-3.6 in sensitive cells, 0.1-0.4 in cells with high (> 70-fold) levels of doxorubicin resistance and 1.2 and 1.9 in cells with low or intermediate (7.5 and 24-fold, respectively) levels of doxorubicin resistance. The change of drug efficacy was reflected by an increase in the total amount of doxorubicin present in the cell at equitoxic (IC50) concentrations. N/C ratios in highly resistant P-glycoprotein-containing cells could be increased with the resistance modifier verapamil to values of 1.3-2.7, a process that was paralleled by a decrease of the cellular doxorubicin amounts present at IC50. At the low to moderate residual levels of resistance, obtained with different concentrations of verapamil, a linear relationship between IC50 and cellular doxorubicin amounts determined at IC50 was found. This shows that at this stage of residual resistance, extra reversal by verapamil should be explained by further increase of drug efficacy rather than by increase of cellular drug accumulation. A similar relationship was found for P-glycoprotein-negative MDR cells with low levels of resistance. Since in these cells N/C ratios could not be altered, verapamil-induced decrease of IC50 must be due to increased drug efficacy by action on as yet unidentified targets. Although the IC50 of sensitive

  18. Tumour markers in urology

    International Nuclear Information System (INIS)

    The same applies essentially also for the bladder carcinomas: There is no reliable marker for these cancers which would be useful for clinical purposes. TPA has proven to be too non-specific in malignoma-detection and therefore hardly facilitates clinical decision-making in individual cases. The CEA is not sensitive enough to be recommendable for routine application. However, in advanced stages a CEA examination may be useful if applied within the scope of therapeutic efforts made to evaluate efficacy. In cases of carcinomas of the prostate the sour prostate-specific phosphatase (SPP) and, more recently, especially the prostate-specific antigen (PSA) have proven in follow-up and therapy monitoring, whereby the PSA is superior to the SPP. Nevertheless, both these markers should be employed in therapy monitoring because differences in behaviour will be observed when the desired treatment effect is only achieved in one of the two markers producing tumour cell clonuses. Both markers, but especially the PSA, are quite reliably in agreement with the result of the introduced chemo-/hormone therapy, whereby an increase may be a sure indicator of relapse several months previous to clinical symptoms, imaging procedures, so-called routine laboratory results and subjective complaints. However, none of the 2 markers is appropriate for the purposes of screening or early diagnosis of carcinomas of the prostate. (orig.)

  19. Common breast cancer susceptibility alleles are associated with tumour subtypes in BRCA1 and BRCA2 mutation carriers: results from the Consortium of Investigators of Modifiers of BRCA1/2

    NARCIS (Netherlands)

    Mulligan, A.M.; Couch, F.J.; Barrowdale, D.; Domchek, S.M.; Eccles, D.; Nevanlinna, H.; Ramus, S.J.; Robson, M.; Sherman, M.; Spurdle, A.B.; Wappenschmidt, B.; Lee, A.; McGuffog, L.; Healey, S.; Sinilnikova, O.M.; Janavicius, R.; Hansen, T.V.; Nielsen, F.C.; Ejlertsen, B.; Osorio, A.; Munoz-Repeto, I.; Duran, M.; Godino, J.; Pertesi, M.; Benitez, J.; Peterlongo, P.; Manoukian, S.; Peissel, B.; Zaffaroni, D.; Cattaneo, E.; Bonanni, B.; Viel, A.; Pasini, B.; Papi, L.; Ottini, L.; Savarese, A.; Bernard, L.; Radice, P.; Hamann, U.; Verheus, M.; Meijers-Heijboer, H.E.; Wijnen, J.; Gomez Garcia, E.B.; Nelen, M.R.; Kets, C.M.; Seynaeve, C.; Tilanus-Linthorst, M.M.; Luijt, R.B. van der; Os, T.V.; Rookus, M.; Frost, D.; Jones, J.L.; Evans, D.G.; Lalloo, F.; Eeles, R.; Izatt, L.; Adlard, J.; Davidson, R.; Cook, J.; Donaldson, A.; Dorkins, H.; Gregory, H.; Eason, J.; Houghton, C.; Barwell, J.; Side, L.E.; McCann, E.; Murray, A.; Peock, S.; Godwin, A.K.; Schmutzler, R.K.; Rhiem, K.; Engel, C.; Meindl, A.; Ruehl, I.; Arnold, N.; Niederacher, D.; Sutter, C.; Deissler, H.; Gadzicki, D.; Kast, K.; Preisler-Adams, S.; Varon-Mateeva, R.; Schoenbuchner, I.; Fiebig, B.; Heinritz, W.; Schafer, D.; Gevensleben, H.; Caux-Moncoutier, V.; Fassy-Colcombet, M.; Cornelis, F.; Mazoyer, S.; Leone, M.; Boutry-Kryza, N.; Hardouin, A.; Berthet, P.; Muller, D.; Fricker, J.P.; Mortemousque, I.; Pujol, P.

    2011-01-01

    ABSTRACT: INTRODUCTION: Previous studies have demonstrated that common breast cancer susceptibility alleles are differentially associated with breast cancer risk for BRCA1 and/or BRCA2 mutation carriers. It is currently unknown how these alleles are associated with different breast cancer subtypes i

  20. Common breast cancer susceptibility alleles are associated with tumour subtypes in BRCA1 and BRCA2 mutation carriers : results from the Consortium of Investigators of Modifiers of BRCA1/2

    NARCIS (Netherlands)

    Mulligan, Anna Marie; Couch, Fergus J.; Barrowdale, Daniel; Domchek, Susan M.; Eccles, Diana; Nevanlinna, Heli; Ramus, Susan J.; Robson, Mark; Sherman, Mark; Spurdle, Amanda B.; Wappenschmidt, Barbara; Lee, Andrew; McGuffog, Lesley; Healey, Sue; Sinilnikova, Olga M.; Janavicius, Ramunas; Hansen, Thomas V. O.; Nielsen, Finn C.; Ejlertsen, Bent; Osorio, Ana; Munoz-Repeto, Ivan; Duran, Mercedes; Godino, Javier; Pertesi, Maroulio; Benitez, Javier; Peterlongo, Paolo; Manoukian, Siranoush; Peissel, Bernard; Zaffaroni, Daniela; Cattaneo, Elisa; Bonanni, Bernardo; Viel, Alessandra; Pasini, Barbara; Papi, Laura; Ottini, Laura; Savarese, Antonella; Bernard, Loris; Radice, Paolo; Hamann, Ute; Verheus, Martijn; Meijers-Heijboer, Hanne E. J.; Wijnen, Juul; Garcia, Encarna B. Gomez; Nelen, Marcel R.; Kets, C. Marleen; Seynaeve, Caroline; Tilanus-Linthorst, Madeleine M. A.; van der Luijt, Rob B.; van Os, Theo; Rookus, Matti; Frost, Debra; Jones, J. Louise; Evans, D. Gareth; Lalloo, Fiona; Eeles, Ros; Izatt, Louise; Adlard, Julian; Davidson, Rosemarie; Cook, Jackie; Donaldson, Alan; Dorkins, Huw; Gregory, Helen; Eason, Jacqueline; Houghton, Catherine; Barwell, Julian; Side, Lucy E.; McCann, Emma; Murray, Alex; Peock, Susan; Godwin, Andrew K.; Schmutzler, Rita K.; Rhiem, Kerstin; Engel, Christoph; Meindl, Alfons; Ruehl, Ina; Arnold, Norbert; Niederacher, Dieter; Sutter, Christian; Deissler, Helmut; Gadzicki, Dorothea; Kast, Karin; Preisler-Adams, Sabine; Varon-Mateeva, Raymonda; Schoenbuchner, Ines; Fiebig, Britta; Heinritz, Wolfram; Schaefer, Dieter; Gevensleben, Heidrun; Caux-Moncoutier, Virginie; Fassy-Colcombet, Marion; Cornelis, Francois; Mazoyer, Sylvie; Leone, Melanie; Boutry-Kryza, Nadia; Hardouin, Agnes; Berthet, Pascaline; Muller, Daniele; Fricker, Jean-Pierre; Mortemousque, Isabelle; Pujol, Pascal; Coupier, Isabelle; Lebrun, Marine; Kientz, Caroline; Longy, Michel; Sevenet, Nicolas; Stoppa-Lyonnet, Dominique; Isaacs, Claudine; Caldes, Trinidad; de la Hoya, Miguel; Heikkinen, Tuomas; Aittomaki, Kristiina; Blanco, Ignacio; Lazaro, Conxi; Barkardottir, Rosa B.; Soucy, Penny; Dumont, Martine; Simard, Jacques; Montagna, Marco; Tognazzo, Silvia; D'Andrea, Emma; Fox, Stephen; Yan, Max; Rebbeck, Tim; Olopade, Olufunmilayo I.; Weitzel, Jeffrey N.; Lynch, Henry T.; Ganz, Patricia A.; Tomlinson, Gail E.; Wang, Xianshu; Fredericksen, Zachary; Pankratz, Vernon S.; Lindor, Noralane M.; Szabo, Csilla; Offit, Kenneth; Sakr, Rita; Gaudet, Mia; Bhatia, Jasmine; Kauff, Noah; Singer, Christian F.; Tea, Muy-Kheng; Gschwantler-Kaulich, Daphne; Fink-Retter, Anneliese; Mai, Phuong L.; Greene, Mark H.; Imyanitov, Evgeny; O'Malley, Frances P.; Ozcelik, Hilmi; Glendon, Gordon; Toland, Amanda E.; Gerdes, Anne-Marie; Thomassen, Mads; Kruse, Torben A.; Jensen, Uffe Birk; Skytte, Anne-Bine; Caligo, Maria A.; Soller, Maria; Henriksson, Karin; Wachenfeldt, von Anna; Arver, Brita; Stenmark-Askmalm, Marie; Karlsson, Per; Ding, Yuan Chun; Neuhausen, Susan L.; Beattie, Mary; Pharoah, Paul D. P.; Moysich, Kirsten B.; Nathanson, Katherine L.; Karlan, Beth Y.; Gross, Jenny; John, Esther M.; Daly, Mary B.; Buys, Saundra M.; Southey, Melissa C.; Hopper, John L.; Terry, Mary Beth; Chung, Wendy; Miron, Alexander F.; Goldgar, David; Chenevix-Trench, Georgia; Easton, Douglas F.; Andrulis, Irene L.; Antoniou, Antonis C.

    2011-01-01

    Introduction: Previous studies have demonstrated that common breast cancer susceptibility alleles are differentially associated with breast cancer risk for BRCA1 and/or BRCA2 mutation carriers. It is currently unknown how these alleles are associated with different breast cancer subtypes in BRCA1 an

  1. Breast reconstruction: State of the arts

    International Nuclear Information System (INIS)

    Radical mastectomy is still required in many cases, such as inflammatory breast cancer, multicentric breast cancer, large tumour volume and small breast size. In this setting, immediate breast reconstruction is more and more offered for breast cancer patients. But such plastic surgery is still debated, owing to risks of implant complications when postoperative radiotherapy of chest wall is mandatory in locoregional breast cancer management. Here, the review is focused on different type of immediate breast reconstruction and on risk of implants complications with or without postoperative radiotherapy. (authors)

  2. Dynamic Contrast Enhanced MRI in Patients With Advanced Breast or Pancreatic Cancer With Metastases to the Liver or Lung

    Science.gov (United States)

    2014-05-28

    Acinar Cell Adenocarcinoma of the Pancreas; Duct Cell Adenocarcinoma of the Pancreas; Liver Metastases; Lung Metastases; Recurrent Breast Cancer; Recurrent Pancreatic Cancer; Stage IV Breast Cancer; Stage IV Pancreatic Cancer

  3. Somatostatin receptor expression, tumour response, and quality of life in patients with advanced hepatocellular carcinoma treated with long-acting octreotide

    OpenAIRE

    Cebon, J

    2006-01-01

    Octreotide may extend survival in hepatocellular carcinoma (HCC). Forty-one per cent of HCCs have high-affinity somatostatin receptors. We aimed to determine the feasibility, safety, and activity of long-acting octreotide in advanced HCC; to identify the best method for assessing somatostatin receptor expression; to relate receptor expression to clinical outcomes; and to evaluate toxicity. Sixty-three patients with advanced HCC received intramuscular long-acting octreotide 20 mg monthly until...

  4. Early identification of non-responding locally advanced breast tumors receiving neoadjuvant chemotherapy

    Science.gov (United States)

    Van de Giessen, Martijn; Schaafsma, Boudewijn E.; Charehbili, Ayoub; Smit, Vincent T. H. B. M.; Kroep, Judith R.; Lelieveldt, Boudewijn P. F.; Liefers, Gerrit-Jan; Chan, Alan; Löwik, Clemens W. G. M.; Dijkstra, Jouke; van de Velde, Cornelis J. H.; Wasser, Martin N. J. M.; Vahrmeijer, Alexander L.

    2015-02-01

    Diffuse optical spectroscopy (DOS) may be advantageous for monitoring tumor response during chemotherapy treatment, particularly in the early treatment stages. In this paper we perform a second analysis on the data of a clinical trial with 25 breast cancer patients that received neoadjuvant chemotherapy. Patients were monitored using delayed contrast enhanced MRI and additionally with diffuse optical spectroscopy at baseline, after 1 cycle of chemotherapy, halfway therapy and before surgery. In this analysis hemoglobin content between tumor tissue and healthy tissue of the same breast is compared on all four monitoring time points. Furthermore, the predictive power of the tumor-healthy tissue difference of HbO2 for non-responder prediction is assessed. The difference in HbO2 content between tumor and healthy tissue was statistically significantly higher in responding tumors than in non-responding tumors at baseline (10.88 vs -0.57 μM, P=0.014) and after one cycle of chemotherapy (6.45 vs -1.31 μM, P=0.048). Before surgery this difference had diminished. In the data of this study, classification on the HbO2 difference between tumor and healthy tissue was able to predict tumor (non-)response at baseline and after 1 cycle with an area-under-curve of 0.95 and 0.88, respectively. While this result suggests that tumor response can be predicted before chemotherapy onset, one should be very careful with interpreting these results. A larger patient population is needed to confirm this finding.

  5. Is palliative resection of the primary tumour, in the presence of advanced rectal cancer, a safe and useful technique for symptom control?

    International Nuclear Information System (INIS)

    Over an 8-year period 22 patients (average age 54 years) underwent rectal resectional surgery in the presence of metastatic disease. There were 13 men and nine women. The commonest complaint was rectal bleeding. All patients had chest radiographs. Pulmonary metastases were identified in four patients. Nineteen abdominal and pelvic computed tomography scans were performed and eight showed evidence of metastases. Skeletal radiographs in two patients showed evidence of bone metastasis. At operation, intraperitoneal metastases were found in 18 patients. Nine of these were not identified preoperatively. Six patients underwent abdomino-perineal resection, nine anterior resection and seven a Hartmann's procedure. Eight patients developed a significant postoperative complication and one died 42 days after surgery. The mean length of hospital stay was 18.6 days. Nine patients received preoperative radiotherapy. Four patients had palliative radiotherapy, two for bony, one for liver and one for peritoneal metastases. Patients were followed up for a mean of 1.1 years. During follow up, 11 returned to the emergency room on 24 occasions. Two patients required readmission. No patient had further rectal bleeding. The mean survival was 1.3 years. It is concluded that patients with rectal cancer and unresectable distant metastases can be successfully palliated by resection of the primary tumour with low morbidity and mortality. The early involvement of a palliative care team facilitates patient management and helps patients enjoy what remains of the rest of their lives at home, in comfort and with good symptom control. Copyright (2004) Blackwell Publishing

  6. From technological advances to biological understanding: The main steps toward high-precision RT in breast cancer.

    Science.gov (United States)

    Leonardi, Maria Cristina; Ricotti, Rosalinda; Dicuonzo, Samantha; Cattani, Federica; Morra, Anna; Dell'Acqua, Veronica; Orecchia, Roberto; Jereczek-Fossa, Barbara Alicja

    2016-10-01

    Radiotherapy improves local control in breast cancer (BC) patients which increases overall survival in the long term. Improvements in treatment planning and delivery and a greater understanding of BC behaviour have laid the groundwork for high-precision radiotherapy, which is bound to further improve the therapeutic index. Precise identification of target volumes, better coverage and dose homogeneity have had a positive impact on toxicity and local control. The conformity of treatment dose due to three-dimensional radiotherapy and new techniques such as intensity modulated radiotherapy makes it possible to spare surrounding normal tissue. The widespread use of dose-volume constraints and histograms have increased awareness of toxicity. Real time image guidance has improved geometric precision and accuracy, together with the implementation of quality assurance programs. Advances in the precision of radiotherapy is also based on the choice of the appropriate fractionation and approach. Adaptive radiotherapy is not only a technical concept, but is also a biological concept based on the knowledge that different types of BC have distinctive patterns of locoregional spread. A greater understanding of cancer biology helps in choosing the treatment best suited to a particular situation. Biomarkers predictive of response play a crucial role. The combination of radiotherapy with molecular targeted therapies may enhance radiosensitivity, thus increasing the cytotoxic effects and improving treatment response. The appropriateness of an alternative fractionation, partial breast irradiation, dose escalating/de-escalating approaches, the extent of nodal irradiation have been examined for all the BC subtypes. The broadened concept of adaptive radiotherapy is vital to high-precision treatments. PMID:27542556

  7. Patterns of relapse in locally advanced breast cancer treated with neoadjuvant chemotherapy followed by surgery and radiotherapy

    Directory of Open Access Journals (Sweden)

    Yadav B

    2007-01-01

    Full Text Available Aims : To define the clinical and pathological predictors of locoregional recurrence (LRR in locally advanced breast cancer (LABC patients treated with neoadjuvant chemotherapy (NACT. Materials and Methods : We retrospectively reviewed the outcome of 141 patients with stage II to stage III carcinoma breast treated at Department of Radiotherapy, PGIMER, Chandigarh from 1998-2002. Mean age of the patients was 46 years, 49% of patients were premenopausal and 51% were postmenopausal. The tumor stage was T2 in 18%; T3 in 61% and T4 in 26% of the patients. NACT regimen given was FAC (5-fluorouracil, adriamycin and cyclophosphamide in 85% and CMF (cyclophosphamide, methotrexate and 5-Fu in 15% patients. Results : After NACT, surgery was possible in 95% patients. Conservative surgery was possible in 23% patients and mastectomy was done in 72% of patients. Pathological complete response (pCR was seen in 18% patients and pathological partial response (pPR in 69% of patients. Stable and progressive disease was seen in 6% and 7% of patients respectively. Adjuvant radiation therapy was given to 86% patients. Six percent patients developed progressive disease and 4% of patients did not turn up for radiation. Five year LRR was 6% and relapse free survival (RFS was 94%. Thirty-two (23% patients developed distant metastasis resulting in distant metastasis free survival of 77%. The factors that correlated positively with LRR on univariate analysis included tumor stage, stage and pathological nodal stage. However, on multivariate analysis, tumor stage and pathological nodal stage were significant. Factors that correlated for distant relapse were tumor stage, response to chemotherapy, type of surgery, extracapsular extension (ECE and tamoxifen therapy. On multivariate analysis only ECE was the significant factor that correlated with distant relapse free survival. Conclusion : Thus, tumor stage and pathological nodal stage remains the most important predictor of LRR

  8. Constitutive gene expression profile segregates toxicity in locally advanced breast cancer patients treated with high-dose hyperfractionated radical radiotherapy

    International Nuclear Information System (INIS)

    Breast cancer patients show a wide variation in normal tissue reactions after radiotherapy. The individual sensitivity to x-rays limits the efficiency of the therapy. Prediction of individual sensitivity to radiotherapy could help to select the radiation protocol and to improve treatment results. The aim of this study was to assess the relationship between gene expression profiles of ex vivo un-irradiated and irradiated lymphocytes and the development of toxicity due to high-dose hyperfractionated radiotherapy in patients with locally advanced breast cancer. Raw data from microarray experiments were uploaded to the Gene Expression Omnibus Database http://www.ncbi.nlm.nih.gov/geo/ (GEO accession GSE15341). We obtained a small group of 81 genes significantly regulated by radiotherapy, lumped in 50 relevant pathways. Using ANOVA and t-test statistical tools we found 20 and 26 constitutive genes (0 Gy) that segregate patients with and without acute and late toxicity, respectively. Non-supervised hierarchical clustering was used for the visualization of results. Six and 9 pathways were significantly regulated respectively. Concerning to irradiated lymphocytes (2 Gy), we founded 29 genes that separate patients with acute toxicity and without it. Those genes were gathered in 4 significant pathways. We could not identify a set of genes that segregates patients with and without late toxicity. In conclusion, we have found an association between the constitutive gene expression profile of peripheral blood lymphocytes and the development of acute and late toxicity in consecutive, unselected patients. These observations suggest the possibility of predicting normal tissue response to irradiation in high-dose non-conventional radiation therapy regimens. Prospective studies with higher number of patients are needed to validate these preliminary results

  9. Superficial hyperthermia in the treatment of locally recurrent or advanced breast cancer - clinical experiences in Prague, Czech Republic

    International Nuclear Information System (INIS)

    Full text: Superficial hyperthermia in combination with radiotherapy represents very effective local treatment of locally recurrent breast cancer. We will present a group of patients treated in our institution since February 2003 to November 2004. The aim of this work is the evaluation of local response to the treatment in our group of patients. Since February 2003 to November 2004 we treated group of 32 women with locally recurrent breast cancer. 24 patients were treated for local recurrence, 5 patients were treated for supraclavicular lymph node metastasis and 3 patients were treated for locally advanced tumor. 27 patients were evaluable for local response and its duration. Hyperthermia was combined with radiotherapy. Radiotherapy was done on 6 MeV linear accelerator, usually using 2 tangential fields with wedges. Dose of radiotherapy was usually 50 Gy/25 fractions (only in the cases of reirradiation with large volume we applied 40 Gy/20 fr). Hyperthermia was done using Lund hyperthermia system for superficial microwave hyperthermia working on 434 MHz and was applied once a week, 5 to 6 applications during the course of radiotherapy, mainly immediately after radiotherapy, for 60 min. The temperature was measured using termistor probes superficially, minimally in the six points. We tried to achieve temperatures in the range from 42 to 43.5oC, but the actually measured temperatures were limited by the tolerance of patients. The anesthetics were not used. We achieved response in 26 from 27 patients. CR on the chest wall or in the supraclavicular region was achieved in 17 cases, PR in 9 cases and in 1 case was seen only stabilization of disease. Duration of response was in range from 3 to 24 months, with median of 9 months. We did not see any serious side effects resulting from hyperthermia treatment, only in the cases of reirradiation we observed slower healing of the post irradiation skin reaction. Superficial hyperthermia represents useful tool for the

  10. Electrochemotherapy of tumours

    International Nuclear Information System (INIS)

    Electrochemotherapy consists of chemotherapy followed by local application of electric pulses to the tumour to increase drug delivery into cells. Drug uptake can be increased by electroporation for only those drugs whose transport through the plasma membrane is impeded. Among many drugs that have been tested so far, only bleomycin and cisplatin found their way from preclinical testing to clinical trials. In vitro studies demonstrated several fold increase of their cytotoxicity after electroporation of cells. In vivo, electroporation of tumours after local or systemic administration of either of the drugs, i.e. electrochemotherapy, proved to be an effective antitumour treatment. In preclinical studies on several tumour models, electrochemotherapy either with bleomycin or cisplatin was elaborated and parameters for effective local tumour control were determined. In veterinary medicine, electrochemotherapy also proved to be effective in the treatment of primary tumours in cats, dogs and horses. In human clinical studies, electrochemotherapy was performed on the patients with progressive disease and accessible tumour nodules of different malignancies. All clinical studies demonstrated that electrochemotherapy is an effective treatment for local tumour control in cancer patients. (author)

  11. Chronic stress in mice remodels lymph vasculature to promote tumour cell dissemination.

    Science.gov (United States)

    Le, Caroline P; Nowell, Cameron J; Kim-Fuchs, Corina; Botteri, Edoardo; Hiller, Jonathan G; Ismail, Hilmy; Pimentel, Matthew A; Chai, Ming G; Karnezis, Tara; Rotmensz, Nicole; Renne, Giuseppe; Gandini, Sara; Pouton, Colin W; Ferrari, Davide; Möller, Andreas; Stacker, Steven A; Sloan, Erica K

    2016-01-01

    Chronic stress induces signalling from the sympathetic nervous system (SNS) and drives cancer progression, although the pathways of tumour cell dissemination are unclear. Here we show that chronic stress restructures lymphatic networks within and around tumours to provide pathways for tumour cell escape. We show that VEGFC derived from tumour cells is required for stress to induce lymphatic remodelling and that this depends on COX2 inflammatory signalling from macrophages. Pharmacological inhibition of SNS signalling blocks the effect of chronic stress on lymphatic remodelling in vivo and reduces lymphatic metastasis in preclinical cancer models and in patients with breast cancer. These findings reveal unanticipated communication between stress-induced neural signalling and inflammation, which regulates tumour lymphatic architecture and lymphogenous tumour cell dissemination. These findings suggest that limiting the effects of SNS signalling to prevent tumour cell dissemination through lymphatic routes may provide a strategy to improve cancer outcomes. PMID:26925549

  12. Molecular mechanisms for tumour resistance to chemotherapy.

    Science.gov (United States)

    Pan, Shu-Ting; Li, Zhi-Ling; He, Zhi-Xu; Qiu, Jia-Xuan; Zhou, Shu-Feng

    2016-08-01

    Chemotherapy is one of the prevailing methods used to treat malignant tumours, but the outcome and prognosis of tumour patients are not optimistic. Cancer cells gradually generate resistance to almost all chemotherapeutic drugs via a variety of distinct mechanisms and pathways. Chemotherapeutic resistance, either intrinsic or acquired, is caused and sustained by reduced drug accumulation and increased drug export, alterations in drug targets and signalling transduction molecules, increased repair of drug-induced DNA damage, and evasion of apoptosis. In order to better understand the mechanisms of chemoresistance, this review highlights our current knowledge of the role of altered drug metabolism and transport and deregulation of apoptosis and autophagy in the development of tumour chemoresistance. Reduced intracellular activation of prodrugs (e.g. thiotepa and tegafur) or enhanced drug inactivation by Phase I and II enzymes contributes to the development of chemoresistance. Both primary and acquired resistance can be caused by alterations in the transport of anticancer drugs which is mediated by a variety of drug transporters such as P-glycoprotein (P-gp), multidrug resistance associated proteins, and breast cancer resistance protein. Presently there is a line of evidence indicating that deregulation of programmed cell death including apoptosis and autophagy is also an important mechanism for tumour resistance to anticancer drugs. Reversal of chemoresistance is likely via pharmacological and biological approaches. Further studies are warranted to grasp the full picture of how each type of cancer cells develop resistance to anticancer drugs and to identify novel strategies to overcome it. PMID:27097837

  13. The efficacy of 89Sr combined with 99Tc-MDP in the treatment of the advanced breast cancers with bone metastases

    Institute of Scientific and Technical Information of China (English)

    Qiuju Lin ; Wenhui Li

    2014-01-01

    Objective: The aim of our study was to evaluate the ef icacy of 89Sr combined with Technetium [99Tc] Methylene-diphosphonate Injection (99Tc-MDP) in the treatment of cancer pain in the advanced breast cancers with bone metastases. Methods: A total of 80 patients with various degrees of bone pain due to multiple metastases of breast cancer were treated with 89Sr combined with 99Tc-MDP. 89Sr was given intravenously at 4mCi on day 1 during the 3-month schedule. After 7 days, 99Tc-MDP was given at 22 mg/day on days 1–10 during the 1-month schedule, for 3 to 6 months. Results: The ef ective rate of relieving pain was 83.75%. The ef ective rate of curing bone metastases was 81.25%. So there was a significant improvement in the quality of life of the patients. Conclusion: 89Sr combined with 99Tc-MDP are ef ective in the treatment of cancer pain in the breast cancers with bone metastasis, and can obviously repair the bone destruction caused by metastases, thereby improving the quality of life in advanced breast cancer patients with bone metastases.

  14. Zinc isotopic compositions of breast cancer tissue.

    OpenAIRE

    Larner, F; Woodley, LN; Shousha, S; Moyes, A; Humphreys-Williams, E; Strekopytov, S; Halliday, AN; Rehkämper, M; Coombes, RC

    2015-01-01

    An early diagnostic biomarker for breast cancer is essential to improve outcome. High precision isotopic analysis, originating in Earth sciences, can detect very small shifts in metal pathways. For the first time, the natural intrinsic Zn isotopic compositions of various tissues in breast cancer patients and controls were determined. Breast cancer tumours were found to have a significantly lighter Zn isotopic composition than the blood, serum and healthy breast tissue in both groups. The Zn i...

  15. TU-F-18C-07: Hardware Advances for MTF Improvement in Dedicated Breast CT

    International Nuclear Information System (INIS)

    Purpose: In this study, we have designed and implemented a prototype dedicated breast CT system (bCT) to improve the spatial resolution characteristics, in order to improve detection of micro-calcifications. Methods: A 10.8 kW water-cooled, tungsten anode x-ray tube, running up to 240 mA at 60 kV, coupled with an x-ray generator specifically designed for this application, and 0.3 mm of added copper filter was used to generate x-ray pulses. A CsI CMOS flat panel detector with a pixel pitch of 0.075 mm in native binning mode was used. The system geometry was designed in a way to achieve an FOV on par with similar bCT prototypes, resulting in a magnification factor of 1.39. A 0.013 mm tungsten wire was used to generate point spread functions. Multiple scans were performed with different numbers of projections, different reconstruction kernel sizes and different reconstruction filters to study the effects of each parameter on MTF. The resulting MTFs were then evaluated quantitatively using the generated PFSs. Duplicate scans with the same parameters were performed on two other dedicated breast CT systems to compare the performance of the new prototype. Results: The results of the MTF experiments demonstrate a significant improvement in the spatial resolution characteristics. In the new prototype, using the pulsed x-ray source results in a restoration of the azimuthal MTF degradation, due to motion blurring previously seen in other bCT systems. Moreover, employing the higher resolution x-ray detector considerably improves the MTF. The MTF at 10% of the new system is at 3.5 1/mm, a factor of 4.36 greater than an earlier bCT scanner. Conclusion: The MTF analysis of the new prototype bCT shows that using the new hardware and control results in a significant improvement in visualization of finer detail. This suggests that the visualization of micro-calcifications will be significantly improved

  16. Tracking metastatic breast cancer: the future of biology in biosensors.

    Science.gov (United States)

    Lim, Y C; Wiegmans, A P

    2016-04-01

    Circulating tumour cells associated with breast cancer (brCTCs) represent cells that have the capability to establish aggressive secondary metastatic tumours. The isolation and characterization of CTCs from blood in a single device is the future of oncology diagnosis and treatment. The methods of enrichment of CTCs have primarily utilized simple biological interactions with bimodal reporting with biased high purity and low numbers or low purity and high background. In this review, we will discuss the advances in microfluidics that has allowed the use of more complex selection criteria and biological methods to identify CTC populations. We will also discuss a potential new method of selection based on the response of the oncogenic DNA repair pathways within brCTCs. This method would allow insight into not only the oncogenic signalling at play but the chemoresistance mechanisms that could guide future therapeutic intervention at any stage of disease progression. PMID:26995223

  17. Improved tumour response by laser light treatment

    Science.gov (United States)

    Graschew, Georgi; Smith, Janice; Rakowsky, Stefan; Roelofs, Theo A.; Schlag, Peter M.; Stein, Ulrike

    2008-04-01

    Multidrug resistance (MDR) poses a serious barrier to the efficacy of clinical treatment of human cancers with chemotherapeutic drugs. This barrier might be reduced and eventually overcome by the simultaneous application of two or more treatment modalities. This study reports on the synergetic effect of combined application of laser light and cytostatic drugs to induce an improved tumour response in MDR cancer cells. The MDR breast cancer cell line MaTu/ADR, resistant to the drug adriamycin (ADR), was treated with a combination of ADR (125-1000 ng/ml) and laser light (488 nm with a total light dose between 6-18 J/cm2). This combined treatment leads to an additional reduction of the cell vitality by a factor of 2-3 as compared to treatment with ADR alone, suggesting that combined application of laser light and other treatment modalities might constitute a promising strategy for improvements in the tumour response.

  18. EGFR and microvessel density in canine malignant mammary tumours.

    Science.gov (United States)

    Carvalho, Maria Isabel; Guimarães, Maria João; Pires, Isabel; Prada, Justina; Silva-Carvalho, Ricardo; Lopes, Carlos; Queiroga, Felisbina L

    2013-12-01

    The epidermal growth factor receptor (EGFR) is a transmembrane tyrosine kinase receptor which has been shown to have an important role in human breast cancer. Its role appears to be associated with increased angiogenesis and metastasis. In order to clarify its role in canine mammary tumours (CMT), 61 malignant neoplasms were studied by using immunohistochemistry, comparing expression of EGFR, microvessel density (MVD) by CD31 immunolabelling and characteristics of tumour aggressiveness. High EGFR immunoexpression was statistically significantly associated with tumour size, tumour necrosis, mitotic grade, histological grade of malignancy and clinical stage. High CD31 immunoreactivity was statistically significantly associated with tubule formation, histological grade of malignancy and clinical stage. A positive correlation between EGFR and CD31 immunoexpression (r = 0.843; P aggression in malignant CMT, presenting the possibility of using EGFR inhibitors in the context of metastatic disease treatment. PMID:24091029

  19. Current role of bone scan with phosphonates in the follow-up of breast cancer

    International Nuclear Information System (INIS)

    A number of studies have demonstrated that bone scintigraphy has high sensitivity and efficacy in the early detection of bone metastases from several tumours, including breast cancer. Bone scintigraphy is the most definitive tool for diagnosing and monitoring metastatic spread of breast cancer. However, in the past decade there has been a wide debate on its impact on survival time, morbidity and quality of life. Worldwide economic restrictions and these studies have led to the adoption of an almost minimalist policy for breast cancer follow-up using evidence-based guidelines. The recommended breast cancer surveillance testing includes only a few procedures (history, physical and breast self-examination, patient education on symptoms, pelvic examination). The routine use of additional tests, such as blood cell count, tumour markers, liver ultrasonography, bone scan and chest X-rays, is not recommended. Accordingly, scintigraphy should be reserved for a limited number of patients. On the other hand, early diagnosis of bone involvement may reduce the risk of skeletal related events, thus leading to a significant improvement in quality of life. Furthermore, new drugs (e.g. bisphosphonates) can now delay the onset of bone metastasis and reduce the number of patients who experience skeletal complications. In conclusion, the evidence of the clinical usefulness of bone scintigraphy (to allow early planning of new treatments in advanced disease) has to be re-evaluated, possibly by large randomised prospective trials. (orig.)

  20. Cardiac tumours in infancy

    OpenAIRE

    Yadava, O.P.

    2012-01-01

    Cardiac tumours in infancy are rare and are mostly benign with rhabdomyomas, fibromas and teratomas accounting for the majority. The presentation depends on size and location of the mass as they tend to cause cavity obstruction or arrhythmias. Most rhabdomyomas tend to regress spontaneously but fibromas and teratomas generally require surgical intervention for severe haemodynamic or arrhythmic complications. Other relatively rare cardiac tumours too are discussed along with an Indian perspect...

  1. AACR Special Conference: Advances in Breast Cancer Research – Genetics, Biology, and Clinical Implications, Huntington Beach, California, USA, 8–12 October 2003

    OpenAIRE

    Welm, Alana L.

    2003-01-01

    The recent meeting 'Advances in Breast Cancer Research – Genetics, Biology, and Clinical Implications' was an American Association for Cancer Research (AACR) Special Conference in Cancer Research, for which the underwriting sponsor was the Avon Foundation. Presentations were made from prominent scientists on several relevant basic science and clinic-oriented topics, including mammary stem cells and development, steroid receptors, matrix and stromal–epithelial interactions, oncogene signaling ...

  2. Role of Tc99m-Sestamibi scintimammography in assessing response to neoadjuvant chemotherapy in patients with locally advanced breast cancer

    OpenAIRE

    Mittal, Bhagwant Rai; Singh, Rajesh K; Kumari, Saumya; Manohar, Kuruva; Bhattacharya, Anish; Singh, Gurpreet

    2012-01-01

    Introduction: Neoadjuvant chemotherapy (NACT) is an essential part of multi-disciplinary management of locally advanced breast cancer (LABC). In this study, we aimed at evaluating the role of Tc99m-Sestamibi scinti-mammography in assessing response to NACT in patients with LABC. Materials and Methods: A total of 42 patients of histologically proven LABC were enrolled in this prospective study. Imaging was performed according to pre-defined protocol at 10 min and 4 h after injection of tracer ...

  3. Treatment characteristics and mortality of a large insured female population with advanced or metastatic breast cancer by receipt of HER2-targeted agents

    Directory of Open Access Journals (Sweden)

    Hao Y

    2015-04-01

    Full Text Available Yanni Hao,1 Nicole Meyer,2 Pamela Landsman-Blumberg,2 William Johnson,2 Jaqueline Willemann Rogerio1 1Novartis Pharmaceuticals Corporation, East Hanover, NJ, USA; 2Truven Health Analytics, Cambridge, MA, USA Purpose: This retrospective administrative claims study of women diagnosed with advanced or metastatic breast cancer compared treatment characteristics and mortality by receipt of human epithelial growth factor receptor 2 (HER2-targeted agents and by disease stage and age group among patients using HER2-targeted agents. Patients and methods: Adult women diagnosed with stage III or IV breast cancer (index date between 2008 and 2012 were identified from MarketScan® databases containing medical and pharmacy claims for >40 million enrollees insured with >100 US health plans. Patients were followed until the earlier of the following: end of enrollment, inpatient death, or December 31, 2012. Study cohorts were women ± HER2-targeted agent use, HER2-targeted agent users' subgroups of stages III and IV, and age group. Pre- and postindex breast cancer treatments were compared among study cohorts. Overall survival was compared using log-rank tests. Cox proportional-hazards models were used to study the predictors of overall survival. Results: Of 30,660 eligible women, 14.4% received HER2-targeted agents. HER2-targeted agent users received more aggressive pre- and postindex cancer treatments compared to those with no HER2-targeted agents. HER2-targeted agents had higher rates of pre- and postindex breast cancer surgery, adjuvant/neoadjuvant chemotherapy, radiation therapy, chemotherapy, and biologics-based therapy. Among HER2-targeted agent users, younger women and those with stage III breast cancer received more aggressive treatments. After adjusting for clinically relevant patient characteristics, women receiving HER2-targeted agents had a 20% reduced risk of death compared to patients not receiving HER2-targeted agents. Among all patients and the

  4. Pituitary tumour clonality revisited.

    Science.gov (United States)

    Clayton, R N; Farrell, W E

    2004-01-01

    Allelotype analysis and X chromosome inactivation analysis in women enables the assessment of tissue clonality, and has demonstrated that the majority of sporadic human pituitary adenomas are monoclonal. This implies that these tumours arise from de novo somatic genetic change(s) in a single pituitary cell. However, clonality within any given tumour may be multiple or single, multiple tumours arising on the background of hyperplasia may be of identical or different clonality, multiple 'sporadic' tumours in a tissue may be of differing clonal origin, and finally morphology cannot predict genetic makeup. These general principles may also apply to the pituitary so it is simplistic to assume that monoclonality is inevitable and that pituitary tumours cannot be multiclonal in origin. Indeed, these observations would be entirely compatible with the initiating stimulus resulting in hyperplasia of specific cell subtypes in the pituitary giving rise to a number of different clones each with variable potential to develop into a discrete tumour depending on their rate of cell division/rate of apotosis. Stimuli might include pituitary-specific oncogenes, intrapituitary growth factors, or extrapituitary trophic factors (e.g. hypothalamic releasing hormones). PMID:15281347

  5. Immunology of naturally transmissible tumours

    OpenAIRE

    Siddle, Hannah V; Kaufman, Jim

    2014-01-01

    Naturally transmissible tumours can emerge when a tumour cell gains the ability to pass as an infectious allograft between individuals. The ability of these tumours to colonise a new host and to cross histocompatibility barriers contradicts our understanding of the vertebrate immune response to allografts. Two naturally occurring contagious cancers are currently active in the animal kingdom, Canine Transmissible Venereal Tumour (CTVT) that spreads among dogs and Devil Facial Tumour Disease (D...

  6. Comparison of vinorelbine plus cisplatin with vinorelbine plus capecitabine in patients with anthracyclines-and taxanes-refractory advanced breast cancer

    Institute of Scientific and Technical Information of China (English)

    Zhendong Zheng; Shuxian Qu; Xiaoxia Chen; Yongye Liu; Ying Piao; Yaling Han; Xiaodong Xie

    2014-01-01

    Objective:The aim of our study was to compare the ef icacy and toxicities of vinorelbine plus cisplatin (NP) regimen with that of vinorelbine plus capecitabine (NX) regimen in the treatment of anthracycline- and taxane-refractory advanced breast cancer. Methods:Forty-six patients with anthracycline-and taxane-refractory advanced breast cancer were equal y randomized into a NP group (n=23) and a NX group (n=23). Response rates and toxicities were evaluated after 2 cycles of chemotherapy. Results:The overal response rate were 48.0%in both groups. There were no significant dif erences in disease control rates (78.0%vs. 83%) or 1-year survival rates (54.6%vs. 55.9%). The main adverse events were bone marrow depression and gastrointestinal reaction, and no significant dif erence was found in toxicities between the groups. Conclusion:For anthracycline-and taxane-refractory advanced breast cancer, NP and NX regimens exerted similar curative ef ects with acceptable toxicity.

  7. Preliminary report. Concomitant irradiation and paclitaxel as radiosensitizer to increase the operability of unresectable locally advanced breast cancer

    International Nuclear Information System (INIS)

    The objective of this non-randomized, single-arm pilot study was to investigate whether paclitaxel (50 mg/m2 body surface area) concomitantly administered with radiation (2 Gy/fr, total 50 Gy) could increase the operability of unresectable locally advanced breast cancer (LABC). Operability was assessed based on the Haagensen criteria, toxicity based on EORTC criteria, and response to therapy based on WHO criteria. Thus far 13 inoperable LABC patients have participated in the study as subjects in the treatment group, and 12 of the cases have been analyzable. As a result of radiopaclitaxel therapy, 10 of the 12 tumors became operable (>83%), and in 3 of the 10 patients there was no evidence of residual tumor. To date there have been no cases of local relapse in the treatment group. Given these results, the preliminary conclusions of the study are as follows: The results of radiochemotherapy, specifically with radiopaclitaxel, are quite promising as a method of treating inoperable LABC by reducing tumor size until it becomes operable. The efficacy and safety of the 50 mg/m2 body surface area dose of paclitaxel were adequate, allowing use of higher doses with the expectation of better results. The schedule of administration in this study yielded effective results. (K.H.)

  8. Prediction of response to chemotherapy in locally advanced breast cancer patients using Tc-99m MIBI scintimammography

    International Nuclear Information System (INIS)

    Locally advanced breast cancer is a common presentation in our part of the world. Down staging of the disease followed by surgery and further therapy has shown to prolong survival in such patients. Early prediction of response to therapy and chemo-resistance is of vital importance to ensure better outcome. The study was done to evaluate the possible role of Tc-99m MIBI scintimammography (MSM) in reliable and early prediction of response to therapy through tracer dynamics of the tumor. Response assessment through clinical criteria and other available modalities was also compared. 16 female patients were evaluated through dynamic and static prone MSM performed before and after two cycles of chemotherapy. Decay corrected washout curves were generated by drawing regions of interest (ROIs) all around the tumor. The tracer washout kinetics of the tumor were studied through half life estimation and tracer retention at 60 minute with reference to peak activity on pre and post therapy studies. Results were subjected to statistical analysis. There was a good correlation between the clinical assessment and dynamic MSM findings in good responders while the dynamic MSM was able to provide better information in poor responders. The results conclude that using tracer kinetics of MSM, early and reliable prediction of response to therapy and chemo-resistance may be possible

  9. Breast Conservation Surgery: State of the Art

    International Nuclear Information System (INIS)

    Breast conservation surgery is available to the vast majority of women with breast cancer. The combination of neoadjuvant therapies and oncoplastic surgical techniques allows even large tumours to be managed with a breast-conserving approach. The relationship between breast size and the volume of tissue to be excised determines the need for volume displacement or replacement. Such an approach can also be used in the management of carefully selected cases of multifocal or multi centric breast cancer. The role of novel techniques, such as endoscopic breast surgery and radiofrequency ablation, is yet to be precisely defined.

  10. Postmastectomy electron-beam-rotation irradiation in locally advanced breast cancer. Prognostic factors of locoregional tumor control

    International Nuclear Information System (INIS)

    Background: Different radiotherapy techniques are used for postmastectomy irradiation. We review the results with the electron-beam-rotation technique in advanced breast cancer patients. Main endpoint was local tumor control. Patients and Methods: From 1990 to 1998 119 patients with adverse pathology features (pT3 17% of patients, pT4 42%, multicentricity 36%, pN≥3 positive nodes and/or pN1biii 81%, close margins 30%) underwent electron-beam-rotation irradiation of the chest wall with daily fractions of 2.0-2.5 Gy per day to 50 Gy total dose after modified radical mastectomy and axillary lymph nodes dissection. A local boost of 10 Gy and/or irradiation of locoregional lymph nodes were applied depending on the completeness of resection and lymph node involvement. Results: After a median follow-up of 73 months for patients at risk the 5-year local tumor control, local tumor control first event, disease-free, and overall survival were 82%, 92%, 57%, and 63% (Kaplan Meier analysis), respectively. Significant predictors of poor local tumor control were maximal tumor diameter ≥5 cm (p=0.01), 'close margins' or residual tumor (p<0.01), four or more involved axillary lymph nodes (p=0.02), two or more involved lymph node levels (p=0.04), negative estrogen receptor status (p=0.03), and high-grade histopathology (GIIb-III, p<0.01). The subgroup analysis showed a high local failure rate of 37% for high-grade (GIIb-III) and estrogen receptor negative tumors, whereas no local recurrence was found in low-grade (GI-IIa) and receptor positive tumors (p=0.01). The multivariate analysis revealed maximal tumor diameter ≥5 cm, four or more involved axillary lymph nodes and high-grade histopathology (GIIb-III) as independent predictors of poor local tumor control. Conclusion: In high-risk breast cancer patients postmastectomy irradiation with the electron-beam-rotation technique is an effective therapy, resulting in a 5-year local failure rate of 8%. Intensified local therapy

  11. Treatment strategies for advanced hormone receptor-positive and human epidermal growth factor 2-negative breast cancer: the role of treatment order.

    Science.gov (United States)

    Perez, Edith A

    2016-01-01

    Although survival rates among patients with breast cancer have improved in recent years, those diagnosed with advanced disease with distant metastasis face a 5-year survival rate of less than 25%, making the management of these patients an area still in significant need of continued research. Selecting the optimal treatment order from among the variety of currently available therapy options presents a relevant challenge for medical oncologists. With the understanding that the majority of patients with breast cancer and those who succumb to this disease have HR-positive disease, this review will focus on treatment options and treatment order in patients with HR-positive advanced breast cancer. While endocrine therapy is considered the preferred treatment for first-line therapy in HR-positive/HER2-negative breast cancer, selection of the specific agent depends on the menopausal status of the patient. Palbociclib, a cyclin-dependent kinase (CDK) 4/6 inhibitor, is also recommended as first-line treatment in patients with ER-positive/HER2-negative disease. In patients with endocrine therapy-resistant disease, specific strategies include sequencing of other antiestrogen receptor agents, or agents that target other molecular pathways. Future treatment strategies for patients with primary or secondary resistance to endocrine therapy for advanced disease are discussed. These strategies include first-line therapy with high-dose fulvestrant or everolimus (in combination with exemestane or letrozole or with other endocrine therapies), use of the PI3K inhibitors (e.g., buparlisib, alpelisib, pictilisib, taselisib), entinostat, CDK 4/6 inhibitors (e.g., palbociclib, ribociclib, abemaciclib), and novel selective estrogen receptor degradation agents that may enhance the targeting of acquired mutations in the ESR1 gene. PMID:26830312

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

    International Nuclear Information System (INIS)

    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

  13. Metastatic renal cell carcinoma presenting as a breast mass in a woman with history of primary breast cancer

    OpenAIRE

    Balliauw, C; Termote, B; Steen, A.; Moerman, P; M. R. Christiaens; Van Ongeval, C

    2011-01-01

    Metastatic extramammary breast tumours are uncommon and differential diagnosis with primary breast carcinoma may prove to be difficult. We report a case of a metastasis of a renal cell cancer in the breast in a woman with a history of primary breast cancer. On follow-up of her breast carcinoma, a lump was detected via mammography and ultrasound. Core needle biopsy revealed a metastatic extramammary lesion originating from an asymptomatic renal cell carcinoma. We conclude that the diagnosis of...

  14. CEF is superior to CMF for tumours with TOP2A aberrations: a Subpopulation Treatment Effect Pattern Plot (STEPP) analysis on Danish Breast Cancer Cooperative Group Study 89D

    DEFF Research Database (Denmark)

    Gunnarsdóttir, Katrín A; Jensen, Maj-Britt; Zahrieh, David;

    2010-01-01

    47:725-734, 2008) demonstrated that superiority of CEF over CMF is limited to patients with TOP2A aberrations, defined as patients whose tumours have TOP2A ratio below 0.8 or above 2.0. The Subpopulation Treatment Effect Pattern Plot (STEPP) technique was applied to these data to explore the pattern...

  15. A comparative study between the effectiveness of chemoendocrine therapy and chemoendocrine therapy combined with radiation for the treatment of advanced and/or recurrent breast cancers

    International Nuclear Information System (INIS)

    The members of the Surgical and Radiation Oncology Group for Breast Cancers have conducted a controlled trial to evaluate the effectiveness of chemoendocrine therapy alone or combined with radiotherapy for advanced and/or recurrent breast cancers. The subjects were divided into two groups, based on the therapeutic regimen: Group A, 18 lesions, received an alternating TAM/MPA plus 5-FU chemotherapy, and Group B, 15 lesions, received this same chemoendocrine therapy combined with radiation (45 to 60 Gy for 4 to 6 weeks). In Group A, 4 out of 18 lesions (22.2%) responsed to the treatment, whereas in Group B, 10 out of 15 (66.7%) responded to the treatment (p=0.0265). Further, in Group A, only 2 lesions (11.1%) achieved a complete remission (CR), whereas in Group B, 9 lesions (60%) achieved a CR (p=0.0094). The incidence of leukopenia, however, was higher in Group B, but this did not affect the continuance of therapy. It was thus concluded that the combined therapy was more effective and contributed to the improvement of a greater number of the advanced and/or recurrent breast cancer cases. (author)

  16. Radiolabelled aptamers for tumour imaging and therapy

    International Nuclear Information System (INIS)

    Full text: The growth in biotechnology has led to new techniques for the design, selection and production of ligands capable of molecular recognition. One promising approach is the production of specific receptor binding molecules based on specific nucleic acid sequences that are capable of recognising a wide array of target molecules. These oligonuclide ligands are known as aptamers. The technology that allows production of aptamer molecules is known as systematic evolution of ligands by exponential enrichment (SELEX). We have used combinatorial chemistry techniques coupled with polymerase chain reaction (PCR) to rapidly select aptamers from degenerate libraries that bind with high affinity and specificity to the protein core of the MUC1 antigen, a tumour marker previously extensively used in tumour imaging and therapy. MUC1 is widely expressed by normal glandular epithelial cells, however this expression is dramatically increased when the cells become malignant. This has been well documented for breast and ovarian cancer, as well as some lung, pancreatic and prostate cancers. Recently it has also been shown that MUC1 is a valuable marker for bladder and has been used for the imaging and targeted therapy of bladder cancer. The aptamer selection process was performed on affinity chromatography matrices. After ten rounds of selection and amplification, aptamers were cloned and sequenced. Post SELEX amino modifications have been used to confer nuclease resistance and coupling potential. The aptamers bound to MUC1 antigen with a Kd of 5nm and high specificity, demonstrated by fluorescent microscopy on MUC1-expressing tumour cells. Using peptide coupling reactions, we have successfully attached chelators for Tc-99m radiolabelling. Two of the constructs tested were based on mono-aptamer chelator complexes, one with commercially available MAG3 and one with a novel designed cyclen-based chelator. The other two constructs were based on the use of multi-aptamer complexes

  17. Breast imaging technology: Recent advances in imaging endogenous or transferred gene expression utilizing radionuclide technologies in living subjects - applications to breast cancer

    International Nuclear Information System (INIS)

    A variety of imaging technologies is being investigated as tools for studying gene expression in living subjects. Two technologies that use radiolabeled isotopes are single photon emission computed tomography (SPECT) and positron emission tomography (PET). A relatively high sensitivity, a full quantitative tomographic capability, and the ability to extend small animal imaging assays directly into human applications characterize radionuclide approaches. Various radiolabeled probes (tracers) can be synthesized to target specific molecules present in breast cancer cells. These include antibodies or ligands to target cell surface receptors, substrates for intracellular enzymes, antisense oligodeoxynucleotide probes for targeting mRNA, probes for targeting intracellular receptors, and probes for genes transferred into the cell. We briefly discuss each of these imaging approaches and focus in detail on imaging reporter genes. In a PET reporter gene system for in vivo reporter gene imaging, the protein products of the reporter genes sequester positron emitting reporter probes. PET subsequently measures the PET reporter gene dependent sequestration of the PET reporter probe in living animals. We describe and review reporter gene approaches using the herpes simplex type 1 virus thymidine kinase and the dopamine type 2 receptor genes. Application of the reporter gene approach to animal models for breast cancer is discussed. Prospects for future applications of the transgene imaging technology in human gene therapy are also discussed. Both SPECT and PET provide unique opportunities to study animal models of breast cancer with direct application to human imaging. Continued development of new technology, probes and assays should help in the better understanding of basic breast cancer biology and in the improved management of breast cancer patients

  18. Breast imaging technology: Application of magnetic resonance imaging to angiogenesis in breast cancer

    International Nuclear Information System (INIS)

    Magnetic resonance imaging (MRI) techniques enable vascular function to be mapped with high spatial resolution. Current methods for imaging in breast cancer are described, and a review of recent studies that compared dynamic contrast-enhanced MRI with histopathological indicators of tumour vascular status is provided. These studies show correlation between in vivo dynamic contrast measurements and in vitro histopathology. Dynamic contrast enhanced MRI is also being applied to assessment of the response of breast tumours to treatment

  19. Primary angiosarcoma of the breast.

    Directory of Open Access Journals (Sweden)

    Sonal TRIPATHI

    2010-06-01

    Full Text Available Breast cancer is increasing and is the most common cancer among females in Brunei Darussalam. Mostare ductal carcinoma. We report a case of a 40-year-old woman who was diagnosed with primary angiosarcomaof the right breast, a rare condition. To the best of our knowledge this is the only reportedcase in Brunei Darussalam. She underwent lumpectomy followed by mastectomy as the resection marginswere not clear. No adjuvant therapy was given because the size of tumour was small, there wasno residual tumour in mastectomy specimen and she had no distant metastasis.

  20. Immunology of naturally transmissible tumours.

    Science.gov (United States)

    Siddle, Hannah V; Kaufman, Jim

    2015-01-01

    Naturally transmissible tumours can emerge when a tumour cell gains the ability to pass as an infectious allograft between individuals. The ability of these tumours to colonize a new host and to cross histocompatibility barriers contradicts our understanding of the vertebrate immune response to allografts. Two naturally occurring contagious cancers are currently active in the animal kingdom, canine transmissible venereal tumour (CTVT), which spreads among dogs, and devil facial tumour disease (DFTD), among Tasmanian devils. CTVT are generally not fatal as a tumour-specific host immune response controls or clears the tumours after transmission and a period of growth. In contrast, the growth of DFTD tumours is not controlled by the Tasmanian devil's immune system and the disease causes close to 100% mortality, severely impacting the devil population. To avoid the immune response of the host both DFTD and CTVT use a variety of immune escape strategies that have similarities to many single organism tumours, including MHC loss and the expression of immunosuppressive cytokines. However, both tumours appear to have a complex interaction with the immune system of their respective host, which has evolved over the relatively long life of these tumours. The Tasmanian devil is struggling to survive with the burden of this disease and it is only with an understanding of how DFTD passes between individuals that a vaccine might be developed. Further,