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Sample records for advanced breast tumours

  1. Extended neoadjuvant chemotherapy in locally advanced breast cancer combined with GM-CSF: effect on tumour-draining lymph node dendritic cells

    NARCIS (Netherlands)

    Pinedo, H.M.; Buter, J.; Luykx-de Bakker, S.A.; Pohlmann, P.R.; Hensbergen, Y. van; Heideman, D.A.M.; Diest, P.J. van; Gruijl, T.D. de; Wall, E. van der

    2003-01-01

    The effect of long-term administration of granulocyte-macrophage colony-stimulating factor (GM-CSF) on dendritic cell (DC) activation and survival in patients with locally advanced breast cancer (LABC) was studied. To this end, the number of activated DC (i.e. positive for the marker S100) in tumour

  2. Comprehensive molecular portraits of human breast tumours.

    Science.gov (United States)

    2012-10-01

    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 subtypes and demonstrated the existence of four main breast cancer classes when combining data from five platforms, each of which shows significant molecular heterogeneity. Somatic mutations in only three genes (TP53, PIK3CA and GATA3) occurred at >10% incidence across all breast cancers; however, there were numerous subtype-associated and novel gene mutations including the enrichment of specific mutations in GATA3, PIK3CA and MAP3K1 with the luminal A subtype. We identified two novel protein-expression-defined subgroups, possibly produced by stromal/microenvironmental elements, and integrated analyses identified specific signalling pathways dominant in each molecular subtype including a HER2/phosphorylated HER2/EGFR/phosphorylated EGFR signature within the HER2-enriched expression subtype. Comparison of basal-like breast tumours with high-grade serous ovarian tumours showed many molecular commonalities, indicating a related aetiology and similar therapeutic opportunities. The biological finding of the four main breast cancer subtypes caused by different subsets of genetic and epigenetic abnormalities raises the hypothesis that much of the clinically observable plasticity and heterogeneity occurs within, and not across, these major biological subtypes of breast cancer.

  3. Breast tumours of adolescents in an African population

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    Umanah Ivy

    2010-01-01

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

  4. Interleukin 18 expression in the primary breast cancer tumour tissue

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    Nahida Srabović

    2011-02-01

    Full Text Available Aim To investigate the presence and expression levels of the IL-18 in the primary breast cancer tissue in relation to the unchangedbreast tissue in same patients and the breast tissue in patients withbenign breast disease, as well as the correlation between the IL-18 expression levels and pathohistological factors, including thecorrelation between IL-18 expression and the estrogens and progesterone receptor status. Methods This prospective randomized study was conducted at the Policlinic for Laboratory Diagnostics of the University Clinical Centre of Tuzla. 50 patients with invasive ductal breast cancer and 20 patients with benign breast diseases were included in the study. The tree-step immunohistochemical staining was used for testing the levels of IL-18 expression and hormone receptor status. Results IL-18 was present in the breast cancer tumour, in the surrounding unchanged tissue of the same patients and in the breast tissue of patients with benign breast tumour and other benign breast disease. The expression of this interleukin was signiicantly higher in breast cancer tumour tissue as compared to its expression in surrounding unchanged tissue of the same patients (p<0,05, whereas IL-18 expression was not signiicantly higher in breast cancer tumours compared to its expression in breast tissue of the patients with benign breast diseases (p=0,057. There was no signiicant correlation between IL-18 expression and the lymph node status, and between IL-18 expression and the pathohistological factors. Conclusion The results suggest possible involvement of IL-18 in complex mechanisms of breast carcinogenesis.

  5. Breast spindle cell tumours: about eight cases

    Directory of Open Access Journals (Sweden)

    Abd El All Howayda S

    2006-07-01

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

  6. 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.

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

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    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.)

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

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    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)

  9. Phyllodes tumours of the breast: a consensus review

    Science.gov (United States)

    Tan, Benjamin Y; Acs, Geza; Apple, Sophia K; Badve, Sunil; Bleiweiss, Ira J; Brogi, Edi; Calvo, José P; Dabbs, David J; Ellis, Ian O; Eusebi, Vincenzo; Farshid, Gelareh; Fox, Stephen B; Ichihara, Shu; Lakhani, Sunil R; Rakha, Emad A; Reis-Filho, Jorge S; Richardson, Andrea L; Sahin, Aysegul; Schmitt, Fernando C; Schnitt, Stuart J; Siziopikou, Kalliopi P; Soares, Fernando A; Tse, Gary M; Vincent-Salomon, Anne; Tan, Puay Hoon

    2016-01-01

    Phyllodes tumours constitute an uncommon but complex group of mammary fibroepithelial lesions. Accurate and reproducible grading of these tumours has long been challenging, owing to the need to assess multiple stratified histological parameters, which may be weighted differently by individual pathologists. Distinction of benign phyllodes tumours from cellular fibroadenomas is fraught with difficulty, due to overlapping microscopic features. Similarly, separation of the malignant phyllodes tumour from spindle cell metaplastic carcinoma and primary breast sarcoma can be problematic. Phyllodes tumours are treated by surgical excision. However, there is no consensus on the definition of an appropriate surgical margin to ensure completeness of excision and reduction of recurrence risk. Interpretive subjectivity, overlapping histological diagnostic criteria, suboptimal correlation between histological classification and clinical behaviour and the lack of robust molecular predictors of outcome make further investigation of the pathogenesis of these fascinating tumours a matter of active research. This review consolidates the current understanding of their pathobiology and clinical behaviour, and includes proposals for a rational approach to the classification and management of phyllodes tumours. PMID:26768026

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

    DEFF Research Database (Denmark)

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

    2008-01-01

    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...... receptor negative tumours. CONCLUSION: The border/centre enhancement difference in malignant breast tumours is easily visualized on midfield dynamic magnetic resonance mammography. The dynamic behaviour is significantly correlated to histological features and receptor status of the tumours Udgivelsesdato...

  11. 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.

  12. Sox2 expression in breast tumours and activation in breast cancer stem cells.

    Science.gov (United States)

    Leis, O; Eguiara, A; Lopez-Arribillaga, E; Alberdi, M J; Hernandez-Garcia, S; Elorriaga, K; Pandiella, A; Rezola, R; Martin, A G

    2012-03-15

    The cancer stem cell (CSC) model does not imply that tumours are generated from transformed tissue stem cells. The target of transformation could be a tissue stem cell, a progenitor cell, or a differentiated cell that acquires self-renewal ability. The observation that induced pluripotency reprogramming and cancer are related has lead to the speculation that CSCs may arise through a reprogramming-like mechanism. Expression of pluripotency genes (Oct4, Nanog and Sox2) was tested in breast tumours by immunohistochemistry and it was found that Sox2 is expressed in early stage breast tumours. However, expression of Oct4 or Nanog was not found. Mammosphere formation in culture was used to reveal stem cell properties, where expression of Sox2, but not Oct4 or Nanog, was induced. Over-expression of Sox2 increased mammosphere formation, effect dependent on continuous Sox2 expression; furthermore, Sox2 knockdown prevented mammosphere formation and delayed tumour formation in xenograft tumour initiation models. Induction of Sox2 expression was achieved through activation of the distal enhancer of Sox2 promoter upon sphere formation, the same element that controls Sox2 transcription in pluripotent stem cells. These findings suggest that reactivation of Sox2 represents an early step in breast tumour initiation, explaining tumour heterogeneity by placing the tumour-initiating event in any cell along the axis of mammary differentiation.

  13. 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.; Gonzalez-Angulo, Ana Maria; Mills, Gordon B.; Dyer, Mary D.; Liu, Shuying; Meng, Xiaolong; Patangan, Modesto; Waldman, Frederic; Stoeppler, Hubert; Rathmell, W. Kimryn; Thorne, Leigh; Huang, Mei; Boice, Lori; Hill, Ashley; Morrison, Carl; Gaudioso, Carmelo; Bshara, Wiam; Daily, Kelly; Egea, Sophie C.; Pegram, Mark D.; Gomez-Fernandez, Carmen; Dhir, Rajiv; Bhargava, Rohit; Brufsky, Adam; Shriver, Craig D.; Hooke, Jeffrey A.; Campbell, Jamie Leigh; Mural, Richard J.; Hu, Hai; Somiari, Stella; Larson, Caroline; Deyarmin, Brenda; Kvecher, Leonid; Kovatich, Albert J.; Ellis, Matthew J.; King, Tari A.; Hu, Hai; Couch, Fergus J.; Mural, Richard J.; Stricker, Thomas; White, Kevin; Olopade, Olufunmilayo; Ingle, James N.; Luo, Chunqing; Chen, Yaqin; Marks, Jeffrey R.; Waldman, Frederic; Wiznerowicz, Maciej; Bose, Ron; Chang, Li-Wei; Beck, Andrew H.; Gonzalez-Angulo, Ana Maria; Pihl, Todd; Jensen, Mark; Sfeir, Robert; Kahn, Ari; Chu, Anna; Kothiyal, Prachi; Wang, Zhining; Snyder, Eric; Pontius, Joan; Ayala, Brenda; Backus, Mark; Walton, Jessica; Baboud, Julien; Berton, Dominique; Nicholls, Matthew; Srinivasan, Deepak; Raman, Rohini; Girshik, Stanley; Kigonya, Peter; Alonso, Shelley; Sanbhadti, Rashmi; Barletta, Sean; Pot, David; Sheth, Margi; Demchok, John A.; Shaw, Kenna R. Mills; Yang, Liming; Eley, Greg; Ferguson, Martin L.; Tarnuzzer, Roy W.; Zhang, Jiashan; Dillon, Laura A. L.; Buetow, Kenneth; Fielding, Peter; Ozenberger, Bradley A.; Guyer, Mark S.; Sofia, Heidi J.; Palchik, Jacqueline D.

    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

  14. 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.

  15. Early prognosis of metastasis risk in inflammatory breast cancer by texture analysis of tumour microscopic images.

    Science.gov (United States)

    Kolarevic, Daniela; Tomasevic, Zorica; Dzodic, Radan; Kanjer, Ksenija; Vukosavljevic, Dragica Nikolic; Radulovic, Marko

    2015-10-01

    Inflammatory breast cancer (IBC) is a rare and aggressive type of locally advanced breast cancer. The purpose of this study was to determine the value of microscopic tumour histomorphology texture for prognosis of local and systemic recurrence at the time of initial IBC diagnosis. This retrospective study included a group of 52 patients selected on the basis of non-metastatic IBC diagnosis, stage IIIB. Gray-Level-Co-Occurrence-Matrix (GLCM) texture analysis was performed on digital images of primary tumour tissue sections stained with haematoxylin/eosin. Obtained values were categorized by use of both data- and outcome-based methods. All five acquired GLCM texture features significantly associated with metastasis outcome. By accuracies of 69-81% and AUCs of 0.71-0.81, prognostic performance of GLCM parameters exceeded that of standard major IBC clinical prognosticators such as tumour grade and response to induction chemotherapy. Furthermore, a composite score consisting of tumour grade, contrast and correlation as independent features resulted in further enhancement of prognostic performance by accuracy of 89%, discrimination efficiency by AUC of 0.93 and an outstanding hazard ratio of 71.6 (95%CI, 41.7-148.4). Internal validation was successfully performed by bootstrap and split-sample cross-validation, suggesting that the model is generalizable. This study indicates for the first time the potential use of primary breast tumour histology texture as a highly accurate, simple and cost-effective prognostic indicator of metastasis risk in IBC. Clinical relevance of the obtained results rests on the role of prognosis in decisions on induction chemotherapy and the resulting impact on quality of life and survival.

  16. Phase contrast imaging of breast tumours with synchrotron radiation

    Energy Technology Data Exchange (ETDEWEB)

    Olivo, A. [Department of Medical Physics and Bioengineering, University College London, Malet Place, Gower Street, London WC1E 6BT (United Kingdom)], E-mail: aolivo@medphys.ucl.ac.uk; Rigon, L. [Istituto Nazionale di Fisica Nucleare, Sezione di Trieste, Area Science Park, Padriciano 99, 34012 Trieste (Italy)], E-mail: rigon@ts.infn.it; Vinnicombe, S.J. [Department of Radiology, St. Bartholomews Hospital, Barts and the London NHS Trust, West Smithfield, London EC1A 7BE (United Kingdom)], E-mail: s.j.vinnicombe@qmul.ac.uk; Cheung, K.C. [STFC Daresbury Laboratory, Keckwick Lane, Warrington, Cheshire WA4 4AD (United Kingdom)], E-mail: k.c.cheung@dl.ac.uk; Ibison, M. [Department of Physics, University of Liverpool, Oxford Street, Liverpool L69 7ZE (United Kingdom)], E-mail: m.ibison@dl.ac.uk; Speller, R.D. [Department of Medical Physics and Bioengineering, University College London, Malet Place, Gower Street, London WC1E 6BT (United Kingdom)], E-mail: rspeller@medphys.ucl.ac.uk

    2009-06-15

    Even though the potential of phase contrast (PC) imaging has been demonstrated in a number of biological tissue samples, the availability of free-space propagation phase contrast images of real breast tumours is still limited. The aim of this study was to obtain phase contrast images of two different pathological breast specimens containing tumours of differing morphological type at two synchrotron radiation (SR) facilities, and to assess any qualitative improvements in the evaluation and characterisation of the masses through the use of phase contrast imaging. A second aim was to assess the effects of parameters such as detector resolution, beam energy and sample-to-detector distance on image quality using the same breast specimens, as to date these effects have been modelled and discussed only for geometric phantoms. At each synchrotron radiation facility a range of images was acquired with different detectors and by varying the above parameters. Images of the same samples were also acquired with the absorption-based approach to allow a direct comparison and estimation of the advantages specifically ascribable to the PC technique.

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

    NARCIS (Netherlands)

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

    2002-01-01

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

  18. 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.

  19. Are ipsilateral breast tumour invasive recurrences in young (more aggressive than their primary tumours?

    Science.gov (United States)

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

    2007-10-22

    The characteristics of ipsilateral breast tumour recurrences (IBTRs) relative to those of their primary tumours (PTs) remain scarcely studied. Of 70 young (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 conserved histological types tended to occur more locally, but not significantly sooner than others. These IBTRs had good concordance for hormone receptors. In discordant cases there were as many losses as appearances of the receptors. The concordance was weak for grades, with equivalent numbers of IBTRs graded lower as higher than their PTs. The 10-year overall survival rate was 70%. Neither the conservation of histological type, location, nor of the two combined were associated with deaths. Early (<2 years) IBTRs, tended to be associated with poorer survival (HR=2.24 (0.92-5.41); P=0.08). IBTRs did not display features of higher aggressiveness than PTs. Neither clinical nor histological definition of a true recurrence could be established other than the conservation of the histological type.

  20. [Therapeutic advances in breast cancer].

    Science.gov (United States)

    Pestalozzi, B C

    2006-04-01

    The treatment of breast cancer has made significant improvements during the past ten years. For early breast cancer with a clinically negative axilla sentinel node biopsy has become the preferred approach. For endocrine therapy of postmenopausal patients the selective aromatase inhibitors have become standard in metastatic as well as in early breast cancer. Trastuzumab (Herceptin) plays an important role in the treatment of HER2-positive breast cancer in the metastatic and since 2005 also in the adjuvant setting. When chemotherapy is used to treat metastatic breast cancer drug combinations are superior to monotherapy only in terms of response rates. By contrast, in the adjuvant setting combination drug therapy is the standard. New methods of tissue analysis including expression patterns of mRNA and proteins are promising research strategies to further advance the field.

  1. 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

  2. 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.

  3. 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.

  4. Relevance of BCAR4 in tamoxifen resistance and tumour aggressiveness of human breast cancer

    NARCIS (Netherlands)

    M.F.E. Godinho (Marcia F.E.); A.M. Sieuwerts (Anieta); M.P. Look (Maxime); D.N. Meijer (Dies); J.A. Foekens (John); L.C.J. Dorssers (Lambert); T.L.A. van Agthoven (Thecla)

    2010-01-01

    textabstractBackground:Breast cancer anti-oestrogen resistance 4 (BCAR4) was identified in a search for genes involved in anti-oestrogen resistance in breast cancer. We explored whether BCAR4 is predictive for tamoxifen resistance and prognostic for tumour aggressiveness, and studied its function.Me

  5. Serum tumour markers as a diagnostic and prognostic tool in Libyan breast cancer.

    Science.gov (United States)

    Elfagieh, Mohamed; Abdalla, Fathi; Gliwan, Asma; Boder, Jamela; Nichols, Wafa; Buhmeida, Abdelbaset

    2012-12-01

    Results from studies on efficacy of carcinoembryonic antigen (CEA), carbohydrate antigen 15.3 (CA 15.3) and thymidine kinase (TK1) as diagnostic and prognostic tools for primary breast cancer (BC) have presented conflicting results, and usefulness of these markers for clinical use in BC remains unclear. The aim of this study is to evaluate potential of concentration of the sera CEA, CA15.3 and TK1 peptides' use as markers in the diagnosis and prognosis of breast lesions of Libyan patients. Serum tumour markers were studied in 20 healthy subjects, 30 patient with benign lesion diseases and 50 patients with histologically confirmed BC diagnosed at the National Cancer Institute (NCI), Misurata, Libya during the period 2005-2009. The concentrations of the BC patients' cutoff points used for diagnostic and prognostic sensitivity were 8.82 ng/ml, 35.57 U/ml and 32.57 U/mg/protein for CEA, CA15.3 and TK1, respectively. Increased CEA (>8.82 ng/ml), CA 15.3 (>35.57 U/ml) and TK1 (>32.57 U/mg/protein) concentrations were found in 62 %, 70 % and 78 % of the BC patients, respectively. For all three tumour markers, increased concentrations correlated increased tumour size and nodal involvement. Significantly higher serum TK1 levels were found in patients with advanced disease (p < 0.0001) and TK1 levels also correlated with disease-specific survival (DSS, p < 0.07). The combined data set of the three markers' data from three markers increased the diagnostic sensitivity to 90 %. The serum marker analysis for CEA, CA 15.3, and S-TK1 concentrations is shown to be a useful tool for identification of malignant cases in our BC population and for the prognostic evaluation of patients with primary BC. Increased concentrations of the markers were also observed to be higher in patients with advanced tumours and indicative of the development of distant metastasis.

  6. Cell-free circulating tumour DNA as a liquid biopsy in breast cancer.

    Science.gov (United States)

    De Mattos-Arruda, Leticia; Caldas, Carlos

    2016-03-01

    Recent developments in massively parallel sequencing and digital genomic techniques support the clinical validity of cell-free circulating tumour DNA (ctDNA) as a 'liquid biopsy' in human cancer. In breast cancer, ctDNA detected in plasma can be used to non-invasively scan tumour genomes and quantify tumour burden. The applications for ctDNA in plasma include identifying actionable genomic alterations, monitoring treatment responses, unravelling therapeutic resistance, and potentially detecting disease progression before clinical and radiological confirmation. ctDNA may be used to characterise tumour heterogeneity and metastasis-specific mutations providing information to adapt the therapeutic management of patients. In this article, we review the current status of ctDNA as a 'liquid biopsy' in breast cancer.

  7. Circulating tumour cells lacking cytokeratin in breast cancer: the importance of being mesenchymal.

    Science.gov (United States)

    Gradilone, Angela; Raimondi, Cristina; Nicolazzo, Chiara; Petracca, Arianna; Gandini, Orietta; Vincenzi, Bruno; Naso, Giuseppe; Aglianò, Anna Maria; Cortesi, Enrico; Gazzaniga, Paola

    2011-05-01

    Circulating tumour cells (CTCs) are independent predictor of prognosis in metastatic breast cancer. Nevertheless, in one third of patients, circulating tumour cells are undetected by conventional methods. Aim of the study was to assess the prognostic value of circulating tumour cells expressing mesenchymal markers in metastatic breast cancer patients. We isolated CTC from blood of 55 metastatic breast cancer patients. CTC were characterized for cytokeratins and markers of epithelial mesenchymal transition. The gain of mesenchymal markers in CTC was correlated to prognosis of patients in a follow-up of 24 months. The presence of mesenchymal markers on CTC more accurately predicted worse prognosis than the expression of cytokeratins alone. Because of the frequent loss of epithelial antigens by CTC, assays targeting epithelial antigens may miss the most invasive cell population. Thus, there is an urgent need to improve detection methods to identify CTC which undergone epithelial mesenchymal transition program.

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

    DEFF Research Database (Denmark)

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

    2010-01-01

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

  9. 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.)

  10. 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.

  11. Annexin A1 influences in breast cancer: Controversies on contributions to tumour, host and immunoediting processes.

    Science.gov (United States)

    Tu, Yan; Johnstone, Cameron N; Stewart, Alastair G

    2017-02-14

    Annexin A1 is a multifunctional protein characterised by its actions in modulating the innate and adaptive immune response. Accumulating evidence of altered annexin A1 expression in many human tumours raises interest in its functional role in cancer biology. In breast cancer, altered annexin A1 expression levels suggest a potential influence on tumorigenic and metastatic processes. However, reports of conflicting results reveal a relationship that is much more complex than first conceptualised. In this review, we explore the diverse actions of annexin A1 on breast tumour cells and various host cell types, including stromal immune and structural cells, particularly in the context of cancer immunoediting.

  12. 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

  13. The Role of CD10 Immunohistochemistry in the Grading of Phyllodes Tumour of The Breast

    Directory of Open Access Journals (Sweden)

    Huzlinda Hussin,Jayalakshmi Pailoor

    2013-08-01

    Full Text Available Objective: To determine the relationship between the degree of CD10 expression in the stromal cells of phyllodes tumour and tumour grading. Methods: A total of 61 cases of mammary phyllodes tumours over the past 11 years were searched from histopathology files, University Malaya Medical Centre. The paraffin blocks were retrieved and 4 μm thick slides were prepared and stained using an antibody against CD10 with the envision method. Fibroadenoma case was used as a control slide and breast myoepithelium as the internal control. Each stained slides was independantly and semiquantitatively analysed for the intensity and percentage of the stromal cells stained. The staining intensity was graded as negative (no staining, mild, moderate and strong if the staining was much weaker, slightly weaker and same intensity as that of the myoepithelium, respectively. The tumour was considered positive for CD10 if the staining intensity is moderate to strong in 20% or more of the stromal cells. Results: 21 (44.7% of 47 benign phyllodes tumour, 5 (83.3% of 6 borderline phyllodes tumour and all 8 cases (100% of malignant phyllodes tumour showed positive expression for CD10 immunostain. Conclusions: There was a significant increase in CD10 expression in the stromal cells as the lesions progressed from benign to borderline and malignant phyllodes tumour. [J Interdiscipl Histopathol 2013; 1(4.000: 195-203

  14. Targeting breast to brain metastatic tumours with death receptor ligand expressing therapeutic stem cells.

    Science.gov (United States)

    Bagci-Onder, Tugba; Du, Wanlu; Figueiredo, Jose-Luiz; Martinez-Quintanilla, Jordi; Shah, Khalid

    2015-06-01

    Characterizing clinically relevant brain metastasis models and assessing the therapeutic efficacy in such models are fundamental for the development of novel therapies for metastatic brain cancers. In this study, we have developed an in vivo imageable breast-to-brain metastasis mouse model. Using real time in vivo imaging and subsequent composite fluorescence imaging, we show a widespread distribution of micro- and macro-metastasis in different stages of metastatic progression. We also show extravasation of tumour cells and the close association of tumour cells with blood vessels in the brain thus mimicking the multi-foci metastases observed in the clinics. Next, we explored the ability of engineered adult stem cells to track metastatic deposits in this model and show that engineered stem cells either implanted or injected via circulation efficiently home to metastatic tumour deposits in the brain. Based on the recent findings that metastatic tumour cells adopt unique mechanisms of evading apoptosis to successfully colonize in the brain, we reasoned that TNF receptor superfamily member 10A/10B apoptosis-inducing ligand (TRAIL) based pro-apoptotic therapies that induce death receptor signalling within the metastatic tumour cells might be a favourable therapeutic approach. We engineered stem cells to express a tumour selective, potent and secretable variant of a TRAIL, S-TRAIL, and show that these cells significantly suppressed metastatic tumour growth and prolonged the survival of mice bearing metastatic breast tumours. Furthermore, the incorporation of pro-drug converting enzyme, herpes simplex virus thymidine kinase, into therapeutic S-TRAIL secreting stem cells allowed their eradication post-tumour treatment. These studies are the first of their kind that provide insight into targeting brain metastasis with stem-cell mediated delivery of pro-apoptotic ligands and have important clinical implications.

  15. Metaplastic breast carcinoma; melanocytic variant, a very rare tumour

    Science.gov (United States)

    Nzegwu, Martin A.; Sule, Emmanuel; Uzoigwe, Joseph; Achi, Franklyn

    2015-01-01

    Metaplastic breast carcinoma (MBC) is a rare heterogeneous malignancy, accounting for <1% of all invasive breast carcinomas, in which adenocarcinoma is found to coexist with an admixture of spindle, squamous, chondroid or bone-forming neoplastic cells. Melanocytic variant was first described by Ruffolo et al. in 1997. We report a case of MBC, melanocytic variant, in a 57-year-old Nigerian female who presented with a left breast mass 8 cm in diameter in the upper outer quadrant, hard and gradually increase in size to become painful. Breast examination showed gross asymmetry. Left breast was oedematous and shiny with extensive peau d'orange. No palpable axillary nodes were seen. Chest X-ray and abdominal ultrasound scan showed no involvement. Breast biopsy revealed an invasive metaplastic ductal carcinoma with melanocytic differentiation. PMID:25666364

  16. 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.

  17. 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.

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

    Energy Technology Data Exchange (ETDEWEB)

    Groves, Ashley M.; Shastry, Manu; Endozo, Raymondo; Ell, Peter J. [University College London, Institute of Nuclear Medicine, London (United Kingdom); Rodriguez-Justo, Manuel [University College London, Department of Histopathology, London (United Kingdom); Malhotra, Anmol; Davidson, Timothy; Kelleher, Tina; Keshtgar, Mohammed R. [Breast Unit, Royal Free Hospital, UCL, London (United Kingdom); Miles, Kenneth A. [Brighton and Sussex University Hospitals, Brighton (United Kingdom)

    2011-01-15

    Tumour angiogenesis is an independent and strong prognostic factor in early breast carcinoma. We performed this study to investigate the ability of {sup 18}F-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 (SUV{sub max}) and mean standardized uptake value (SUV{sub mean}). 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 SUV{sub max} 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 SUV{sub mean} 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 {sup 18}F-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, {sup 18}F-FDG PET may have a role in the management of primary breast cancer patients even in early-stage disease. (orig.)

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

    Directory of Open Access Journals (Sweden)

    Elham Saniei

    2016-11-01

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

  20. Primary breast cancer tumours contain high amounts of IgA1 immunoglobulin: an immunohistochemical analysis of a possible carrier of the tumour-associated Tn antigen.

    Directory of Open Access Journals (Sweden)

    Charlotte Welinder

    Full Text Available 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. The short O-glycan that forms the antigen is carried by a number of different proteins. One potential carrier of the Tn antigen is immunoglobulin A1 (IgA1, which we surprisingly found in tumour cells of the invasive parts of primary breast carcinoma. Conventional immunohistochemical analysis of paraffin-embedded sections from primary breast cancers showed IgA1 to be present in the cytoplasm and plasma membrane of 35 out of 36 individual primary tumours. The immunohistochemical staining of HPA and anti-Tn antibody (GOD3-2C4 did to some extent overlap with the presence of IgA1 in the tumours, but differences were seen in the percentage of stained cells and in the staining pattern in the different breast cancers analysed. Anti-Tn antibody and HPA were also shown to specifically bind to a number of possible constellations of the Tn antigen in the hinge region of IgA1. Both reagents could also detect the presence of Tn positive IgA in serum. On average 51% of the tumour cells in the individual breast cancer tumour sections showed staining for IgA1. The overall amount of staining in the invasive part of the tumour with the anti Tn antibody was 67%, and 93% with HPA. The intra-expression or uptake of IgA1 in breast cancer makes it a new potential carrier of the tumour associated and immunogenic Tn antigen.

  1. 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.

  2. 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.)

  3. 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.

  4. Modelling circulating tumour cells for personalised survival prediction in metastatic breast cancer.

    Directory of Open Access Journals (Sweden)

    Gianluca Ascolani

    2015-05-01

    Full Text Available Ductal carcinoma is one of the most common cancers among women, and the main cause of death is the formation of metastases. The development of metastases is caused by cancer cells that migrate from the primary tumour site (the mammary duct through the blood vessels and extravasating they initiate metastasis. Here, we propose a multi-compartment model which mimics the dynamics of tumoural cells in the mammary duct, in the circulatory system and in the bone. Through a branching process model, we describe the relation between the survival times and the four markers mainly involved in metastatic breast cancer (EPCAM, CD47, CD44 and MET. In particular, the model takes into account the gene expression profile of circulating tumour cells to predict personalised survival probability. We also include the administration of drugs as bisphosphonates, which reduce the formation of circulating tumour cells and their survival in the blood vessels, in order to analyse the dynamic changes induced by the therapy. We analyse the effects of circulating tumour cells on the progression of the disease providing a quantitative measure of the cell driver mutations needed for invading the bone tissue. Our model allows to design intervention scenarios that alter the patient-specific survival probability by modifying the populations of circulating tumour cells and it could be extended to other cancer metastasis dynamics.

  5. 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.

  6. Impact of tumour epithelial subtype on circulating microRNAs in breast cancer patients.

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    Peadar S Waters

    Full Text Available While a range of miRNAs have been shown to be dysregulated in the circulation of patients with breast cancer, little is known about the relationship between circulating levels and tumour characteristics. The aim of this study was to analyse alterations in circulating miRNA expression during tumour progression in a murine model of breast cancer, and to detemine the clinical relevance of identified miRNAs at both tissue and circulating level in patient samples. Athymic nude mice received a subcutaneous or mammary fat pad injection of MDA-MB-231 cells. Blood sampling was performed at weeks 1, 3 and 6 following tumour induction, and microRNA extracted. MicroRNA microArray analysis was performed comparing samples harvested at week 1 to those collected at week 6 from the same animals. Significantly altered miRNAs were validated across all murine samples by RQ-PCR (n = 45. Three miRNAs of interest were then quantified in the circulation(n = 166 and tissue (n = 100 of breast cancer patients and healthy control individuals. MicroArray-based analysis of murine blood samples revealed levels of 77 circulating microRNAs to be changed during disease progression, with 44 demonstrating changes >2-fold. Validation across all samples revealed miR-138 to be significantly elevated in the circulation of animals during disease development, with miR-191 and miR-106a levels significantly decreased. Analysis of patient tissue and blood samples revealed miR-138 to be significantly up-regulated in the circulation of patients with breast cancer, with no change observed in the tissue setting. While not significantly changed overall in breast cancer patients compared to controls, circulating miR-106a and miR-191 were significantly decreased in patients with basal breast cancer. In tissue, both miRNAs were significantly elevated in breast cancer compared to normal breast tissue. The data demonstrates an impact of tumour epithelial subtype on circulating levels of

  7. Advances in the surgical treatment of breast cancer and postoperative physiotherapy

    Directory of Open Access Journals (Sweden)

    Anna Opuchlik

    2016-07-01

    Full Text Available In recent years, radical surgical techniques have been replaced with conserving ones, and a sentinel lymph node biopsy was introduced in the case of routine lymphadenectomy. Subcutaneous amputation with an immediate breast reconstruction or radical breast amputation in Madden modification are used in advanced tumours. Breast conserving surgery and effective neoadjuvant therapy reduce the range of the operation and postoperative complications. Similarly, breast reconstructions do not increase the risk of cancer development, and they do not impede the detection of a local recurrence. This paper presents the most commonly used types of surgery used to treat breast cancer, and the possibility of a surgical reconstruction of the breast. The methods of physiotherapeutic management in particular stages of treating women both after radical surgeries and reconstructions, including the aspect of maintaining their physical activity and mental balance are discussed.

  8. 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

  9. Monitoring different stages of breast cancer using tumour markers CA 15-3, CEA and TPA

    DEFF Research Database (Denmark)

    Sölétormos, G; Nielsen, D; Schiøler, V;

    2004-01-01

    % of the patients receiving first-line chemotherapy (cohort B). Trials are necessary to determine whether tumour marker-guided therapy has any prognostic impact. The data suggest that tumour marker information may be used to stop ineffective treatments and reduce unnecessary adverse effects.......-individual biological variation, and the rate of increase. Patient cohorts were as follows: (A) 90 stage II breast cancer patients who were monitored postoperatively, (B) 204 recurrent breast cancer patients who were monitored during first-line chemotherapy, and (C) 112 patients who were monitored during the time...... period after first-line chemotherapy. The sensitivity for progression was 44% (cohort A), 69% (cohort B), and 68% (cohort C) without any false progression signals. Marker lead-times exceeded 3 months in 20% (cohort A) and 27% (cohort C) of patients. Marker lead-times were 1-6 months among 33...

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

    OpenAIRE

    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. Age is an important risk factor. The incidence climbs after age 30, followed by a slight dip at menopause and continues to ri se during postmenopausal years. Honnonal influences are weil documente...

  11. Medical therapy of advanced malignant epithelial tumours of the ovary.

    Science.gov (United States)

    Colombo, N; Parma, G; Bocciolone, L; Franchi, D; Sideri, M; Maggioni, A

    2000-01-01

    quality of life and symptoms; ii. tumour load reduction and survival advantage; iii. evaluation of potentially active new drugs to be included in first-line. Since the goal is palliation in most cases, monotherapy is generally indicated. However, the chances of response are directly related to the treatment-free interval, with a response rate nearly equivalent to that of primary chemotherapy when the treatment-free interval exceeds 24 months. Extension of the platinum-free interval before re-treatment with platinum or taxanes may allow partial reversal of resistance to these agents which can therefore still show significant activity in relapsing patients. Unfortunately, durable response to salvage chemotherapy is rare and cure is almost impossible. The sequential use of the agents currently available for salvage treatment in monotherapy may transform ovarian cancer into a chronic disease and confers long survival to the patients. Perhaps, the most interesting role of second-line chemotherapy is to identify new potentially active drugs, which can be moved up-front. Most of the compounds used in second line (gemcitabine, topotecan, liposomal doxorubicin) are in fact under investigation to develop alternative schedules and sequences of drug administration. A new phase III multi-national randomised study for patients with advanced stage epithelial ovarian or primary periperitoneal carcinoma will evaluate the impact of incorporating a new drug within either a platinum-based triplet (new drug + platinum + PTX) or a sequential-doublet (new drug + platinum followed by platinum + PTX) in order to identify one or more experimental regimens able to improve long-term survival with acceptable toxicity.

  12. 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.

  13. 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.)

  14. Malignant change in a massive pleomorphic adenoma resembling the presentation of advanced inflammatory breast cancer.

    Science.gov (United States)

    Seager, Leonie; Colbert, Serryth; Spedding, Anne V; Brennan, Peter A

    2012-04-01

    Massive tumours of the parotid are uncommon as due to their site, they are usually removed at an earlier stage. We present a bizarre case of a carcinoma ex-pleomorphic adenoma which mimicked an advanced breast cancer, complete with a 'nipple-like' extension and peau d'orange changes in the overlying skin as a result of a dense dermal inflammatory response. A procedure akin to a mastectomy with facial nerve preservation was carried out for removal. To our knowledge, peau d'orange has not been reported before in parotid tumours.

  15. Role of CD10 Immunoexpression in Grading Phyllodes Tumour of the Breast

    Science.gov (United States)

    Khandeparkar, Siddhi Gaurish Sinai; Joshi, Avinash R; Kothikar, Vishakha; Nasare, Anuja; Patil, Sukhada; Niraspatil, Supriya; Dhande, Bhagyashree

    2017-01-01

    Introduction Fibroepithelial tumours are a heterogeneous group of biphasic neoplasms consisting of a proliferation of both epithelial and stromal components. Fibroadenoma (FA) and Phyllodes Tumour (PT) constitute the major entities. It is crucial to distinguish benign from borderline PT (low grade malignant PT), because the former do not metastasize, have a lesser risk of local recurrence and initial local recurrences are histologically benign in almost all instances. Multiple Immunohistochemical (IHC) markers are being studied to find their utility in grading the PT accurately for planning proper treatment. Aim To study, the IHC expression of CD10 in the stromal cells of a series of PTs and FA, with the aim of determining whether the degree of CD10 expression in the stromal cells is related to the grade of the tumour. Materials and Methods Records of 28 cases of PT and 35 cases of FA received in the Department of Pathology in a tertiary care hospital were obtained. Histopathology reports and slides of all the cases were reviewed and clinical data such as age and histomorphological features such as tumour cellularity, stromal overgrowth, mitotic count and nuclear atypia were noted. Representative block of the tumour with maximum cellularity was subjected to CD10 staining. For FA and benign PT a technique of tissue microarray was used. For borderline and malignant PT, representative section was used. Stromal cell staining was assessed, using cytoplasmic staining of the breast myoepithelium as internal control. Results Present study included 35 cases of FA, 20 cases of benign PT, five cases of borderline PT and three cases of malignant PT. The mean age of the patients increased with the increasing tumour grade of PT and this was also observed for FA and benign PT. The mean age increased with increase in tumour grade of PT and was statistically significant (p<0.05). The mean size did not increase with the increasing tumour grade of PT and was statistically

  16. Aromatase inhibitors for treatment of advanced breast cancer in postmenopausal women.

    OpenAIRE

    2009-01-01

    BACKGROUND: Hormonal treatments for advanced or metastatic breast cancer, such as tamoxifen and the progestins megestrol acetate and medroxyprogesterone acetate, have been in use for many years. Aromatase inhibitors (AIs) are a class of compounds that systemically inhibit oestrogen synthesis in the peripheral tissues. Aminoglutethimide was the first AI in clinical use (first generation) and had a similar tumour-regressing effect to other endocrine treatments, which showed the potential of thi...

  17. Breast cancer nodal metastasis correlates with tumour and lymph node methylation profiles of Caveolin-1 and CXCR4.

    Science.gov (United States)

    Alevizos, Leonidas; Kataki, Agapi; Derventzi, Anastasia; Gomatos, Ilias; Loutraris, Christos; Gloustianou, Georgia; Manouras, Andreas; Konstadoulakis, Manousos M; Zografos, George

    2014-06-01

    DNA methylation is the best characterised epigenetic change so far. However, its role in breast cancer metastasis has not as yet been elucidated. The aim of this study was to investigate the differences between the methylation profiles characterising primary tumours and their corresponding positive or negative for metastasis lymph nodes (LN) and correlate these with tumour metastatic potential. Methylation signatures of Caveolin-1, CXCR4, RAR-β, Cyclin D2 and Twist gene promoters were studied in 30 breast cancer primary lesions and their corresponding metastasis-free and tumour-infiltrated LN with Methylation-Specific PCR. CXCR4 and Caveolin-1 expression was further studied by immunohistochemistry. Tumours were typified by methylation of RAR-β and hypermethylation of Cyclin-D2 and Twist gene promoters. Tumour patterns were highly conserved in tumour-infiltrated LN. CXCR4 and Caveolin-1 promoter methylation patterns differentiated between node-negative and metastatic tumours. Nodal metastasis was associated with tumour and lymph node profiles of extended methylation of Caveolin-1 and lack of CXCR4 hypermethylation. Immunodetection studies verified CXCR4 and Caveolin-1 hypermethylation as gene silencing mechanism. Absence of Caveolin-1 expression in stromal cells associated with tumour aggressiveness while strong Caveolin-1 expression in tumour cells correlated with decreased 7-year disease-free survival. Methylation-mediated activation of CXCR4 and inactivation of Caveolin-1 was linked with nodal metastasis while intratumoral Caveolin-1 expression heterogeneity correlated with disease progression. This evidence contributes to the better understanding and, thereby, therapeutic management of breast cancer metastasis process.

  18. 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......-embedded sections from primary breast cancers showed IgA1 to be present in the cytoplasm and plasma membrane of 35 out of 36 individual primary tumours. The immunohistochemical staining of HPA and anti-Tn antibody (GOD3-2C4) did to some extent overlap with the presence of IgA1 in the tumours, but differences were...... seen in the percentage of stained cells and in the staining pattern in the different breast cancers analysed. Anti-Tn antibody and HPA were also shown to specifically bind to a number of possible constellations of the Tn antigen in the hinge region of IgA1. Both reagents could also detect the presence...

  19. Breast cancer. Part 3: advanced cancer and psychological implications.

    Science.gov (United States)

    Harmer, Victoria

    This is the last article in this 3-part series on breast cancer. The previous two articles have outlined the principles behind breast awareness and breast health, detailing common benign breast diseases, types of breast cancer and staging, and treatment for breast cancer, including surgery, chemotherapy, radiotherapy and endocrine treatment. The series concludes by giving information on advanced disease, including when a patient presents late with a fungating breast lesion, or if the disease has metastasized from the breast to other organs. Lymphoedema is also described and discussed, and the latter half of this article discusses psychological implications of breast cancer, from diagnosis through the individual treatments.

  20. Aberrant Promoter Methylation of the Tumour Suppressor RASSF10 and Its Growth Inhibitory Function in Breast Cancer

    Directory of Open Access Journals (Sweden)

    Antje M. Richter

    2016-02-01

    Full Text Available Breast cancer is the most common cancer in women, with 1.7 million new cases each year. As early diagnosis and prognosis are crucial factors in cancer treatment, we investigated potential DNA methylation biomarkers of the tumour suppressor family Ras-association domain family (RASSF. Promoter hypermethylation of tumour suppressors leads to their inactivation and thereby promotes cancer development and progression. In this study we analysed the tumour suppressors RASSF1A and RASSF10. Our study shows that RASSF10 is expressed in normal breast but inactivated by methylation in breast cancer. We observed a significant inactivating promoter methylation of RASSF10 in primary breast tumours. RASSF10 is inactivated in 63% of primary breast cancer samples but only 4% of normal control breast tissue is methylated (p < 0.005. RASSF1A also shows high promoter methylation levels in breast cancer of 56% vs. 8% of normal tissue (p < 0.005. Interestingly more than 80% of breast cancer samples harboured a hypermethylation of RASSF10 and/or RASSF1A promoter. Matching samples exhibited a strong tumour specific promoter methylation of RASSF10 in comparison to the normal control breast tissue. Demethylation treatment of breast cancer cell lines MCF7 and T47D reversed RASSF10 promoter hypermethylation and re-established RASSF10 expression. In addition, we could show the growth inhibitory potential of RASSF10 in breast cancer cell lines MCF7 and T47D upon exogenous expression of RASSF10 by colony formation. We could further show, that RASSF10 induced apoptotic changes in MCF7 and T47D cells, which was verified by a significant increase in the apoptotic sub G1 fraction by 50% using flow cytometry for MCF7 cells. In summary, our study shows the breast tumour specific inactivation of RASSF10 and RASSF1A due to DNA methylation of their CpG island promoters. Furthermore RASSF10 was characterised by the ability to block growth of breast cancer cell lines by apoptosis

  1. Tumour location and axillary lymph node involvement in breast cancer: a series of 3472 cases from Sweden

    DEFF Research Database (Denmark)

    Manjer, J; Balldin, G; Garne, J P

    2004-01-01

    AIM: This study investigates the potential relation between breast cancer location and axillary lymph node involvement (ALNI). METHODS: Out of all cases with unilateral first-time diagnosis of invasive breast cancer in Malmö, Sweden, between 1961 and 1991, 3472 underwent axillary dissection. The .......19-2.18), and for central tumours 3.50 (2.32-5.28). CONCLUSIONS: Outer and central breast tumours are associated with a high risk of axillary lymph node involvement. Udgivelsesdato: 2004-Aug......AIM: This study investigates the potential relation between breast cancer location and axillary lymph node involvement (ALNI). METHODS: Out of all cases with unilateral first-time diagnosis of invasive breast cancer in Malmö, Sweden, between 1961 and 1991, 3472 underwent axillary dissection...

  2. Tumour suppressor function of MDA-7/IL-24 in human breast cancer

    Directory of Open Access Journals (Sweden)

    Patani Neill

    2010-08-01

    Full Text Available Abstract Introduction Melanoma differentiation associated gene-7 (MDA-7, also known as interleukin (IL-24, is a tumour suppressor gene associated with differentiation, growth and apoptosis. However, the mechanisms underlying its anti-neoplastic activity, tumour-specificity and efficacy across a spectrum of human cancers have yet to be fully elucidated. In this study, the biological impact of MDA-7 on the behavior of breast cancer (BC cells is evaluated. Furthermore, mRNA expression of MDA-7 is assessed in a cohort of women with BC and correlated with established pathological parameters and clinical outcome. Methods The human BC cell line MDA MB-231 was used to evaluate the in-vitro impact of recombinant human (rh-MDA-7 on cell growth and motility, using a growth assay, wounding assay and electric cell impedance sensing (ECIS. Localisation of MDA-7 in mammary tissues was assessed with standard immuno-histochemical methodology. BC tissues (n = 127 and normal tissues (n = 33 underwent RNA extraction and reverse transcription, MDA-7 transcript levels were determined using real-time quantitative PCR. Transcript levels were analyzed against tumour size, grade, oestrogen receptor (ER status, nodal involvement, TNM stage, Nottingham Prognostic Index (NPI and clinical outcome over a 10 year follow-up period. Results Exposure to rh-MDA-7 significantly reduced wound closure rates for human BC cells in-vitro. The ECIS model demonstrated a significantly reduced motility and migration following rh-MDA-7 treatment (p = 0.024. Exposure to rh-MDA-7 was only found to exert a marginal effect on growth. Immuno-histochemical staining of human breast tissues revealed substantially greater MDA-7 positivity in normal compared to cancer cells. Significantly lower MDA-7 transcript levels were identified in those predicted to have a poorer prognosis by the NPI (p = 0.049 and those with node positive tumours. Significantly lower expression was also noted in tumours from

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

    DEFF Research Database (Denmark)

    Vitak, B; Olsen, K E; Månson, J C;

    1999-01-01

    rate of patients with interval cancer and the interval between the latest screen and diagnosis, tumour characteristics and radiological category of the interval tumours. The study focused on comparison of patients with true interval and missed interval cancer. Women with mammographically occult tumours...... screen and diagnosis were not genuine predictors of the prognosis in patients with invasive interval breast cancer. No certain prognostic difference existed between true interval cancers and overlooked or misinterpreted interval breast cancers, despite higher proportions of grade-I tumours, ER positive......The aim of this study was to investigate whether different mammographic categories of interval cancer classified according to findings at the latest screening are associated with different distributions of prognostic factors or with different survival rates. The series consisted of all patients...

  5. 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.

  6. 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.

  7. Solutions of Inverse Problems with Potential Application for Breast Tumour Detection Using Microwave Measurements

    Directory of Open Access Journals (Sweden)

    G. G. Senaratne

    2007-01-01

    Full Text Available This paper presents one-dimensional and two-dimensional microwave inverse computing methods to detect an internal object using measurements based on a signal applied from the surface of the host material. The modelling of our application system has been aimed towards the in vivo detection of a breast tumour, in particular, and to enable the calculation of the tumour size and its distance from the surface of the breast. However, our approach is also applicable for more general foreign object identification. Complex backscattered electromagnetic waves characterise the relations of the internal properties of the host material. Forward and backscattered signals are used to calculate the impedance and reflection coefficients as a function of the applied microwave frequency. In the study of one-dimensional modelling, we discuss the approach to identifying a foreign object hidden inside the host material and we present a method for computing the distance to the object from the surface of the host. Subsequently, a cylindrical coordinate system is used for two-dimensional modelling. A method to compute the size of the object (up to one millimetre in radius is discussed. Computation of unknown electrical and non-electrical parameters using front-end microwave application is challenging but it is feasible.

  8. 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.

  9. DMP1β, a splice isoform of the tumour suppressor DMP1 locus, induces proliferation and progression of breast cancer.

    Science.gov (United States)

    Maglic, Dejan; Stovall, Daniel B; Cline, J Mark; Fry, Elizabeth A; Mallakin, Ali; Taneja, Pankaj; Caudell, David L; Willingham, Mark C; Sui, Guangchao; Inoue, Kazushi

    2015-05-01

    Our recent work has indicated that the DMP1 locus on 7q21, encoding a haplo-insufficient tumour suppressor, is hemizygously deleted at a high frequency in breast cancer. The locus encodes DMP1α protein, an activator of the p53 pathway leading to cell cycle arrest and senescence, and two other functionally undefined isoforms, DMP1β and DMP1γ. In this study, we show that the DMP1 locus is alternatively spliced in ∼30% of breast cancer cases with relatively decreased DMP1α and increased DMP1β expression. RNA-seq analyses of a publicly available database showed significantly increased DMP1β mRNA in 43-55% of human breast cancers, dependent on histological subtypes. Similarly, DMP1β protein was found to be overexpressed in ∼60% of tumours relative to their surrounding normal tissue. Importantly, alteration of DMP1 splicing and DMP1β overexpression were associated with poor clinical outcomes of the breast cancer patients, indicating that DMP1β may have a biological function. Indeed, DMP1β increased proliferation of non-tumourigenic mammary epithelial cells and knockdown of endogenous DMP1 inhibited breast cancer cell growth. To determine DMP1β's role in vivo, we established MMTV-DMP1β transgenic mouse lines. DMP1β overexpression was sufficient to induce mammary gland hyperplasia and multifocal tumour lesions in mice at 7-18 months of age. The tumours formed were adenosquamous carcinomas with evidence of transdifferentiation and keratinized deposits. Overall, we identify alternative splicing as a mechanism utilized by cancer cells to modulate the DMP1 locus through diminishing DMP1α tumour suppressor expression, while simultaneously up-regulating the tumour-promoting DMP1β isoform.

  10. Early clinical investigation of sulofenur with a daily schedule in advanced solid tumours

    DEFF Research Database (Denmark)

    Krarup-Hansen, A; Pedersen, H; Andersen, E

    1997-01-01

    modification for the individual patient at any given dose level; 38 patients with advanced solid malignant tumours were enrolled. Haemolytic anaemia was the main side effect. The toxicity was marked at dose levels of 600 and 700 mg/m2. Moderate methaemoglobinaemia also occurred. One case of reversible toxic...

  11. 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.)

  12. 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 expression of proliferation-related 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

  13. The genomic and transcriptomic architecture of 2,000 breast tumours reveals novel subgroups.

    Science.gov (United States)

    Curtis, Christina; Shah, Sohrab P; Chin, Suet-Feung; Turashvili, Gulisa; Rueda, Oscar M; Dunning, Mark J; Speed, Doug; Lynch, Andy G; Samarajiwa, Shamith; Yuan, Yinyin; Gräf, Stefan; Ha, Gavin; Haffari, Gholamreza; Bashashati, Ali; Russell, Roslin; McKinney, Steven; Langerød, Anita; Green, Andrew; Provenzano, Elena; Wishart, Gordon; Pinder, Sarah; Watson, Peter; Markowetz, Florian; Murphy, Leigh; Ellis, Ian; Purushotham, Arnie; Børresen-Dale, Anne-Lise; Brenton, James D; Tavaré, Simon; Caldas, Carlos; Aparicio, Samuel

    2012-04-18

    The elucidation of breast cancer subgroups and their molecular drivers requires integrated views of the genome and transcriptome from representative numbers of patients. We present an integrated analysis of copy number and gene expression in a discovery and validation set of 997 and 995 primary breast tumours, respectively, with long-term clinical follow-up. Inherited variants (copy number variants and single nucleotide polymorphisms) and acquired somatic copy number aberrations (CNAs) were associated with expression in ~40% of genes, with the landscape dominated by cis- and trans-acting CNAs. By delineating expression outlier genes driven in cis by CNAs, we identified putative cancer genes, including deletions in PPP2R2A, MTAP and MAP2K4. Unsupervised analysis of paired DNA–RNA profiles revealed novel subgroups with distinct clinical outcomes, which reproduced in the validation cohort. These include a high-risk, oestrogen-receptor-positive 11q13/14 cis-acting subgroup and a favourable prognosis subgroup devoid of CNAs. Trans-acting aberration hotspots were found to modulate subgroup-specific gene networks, including a TCR deletion-mediated adaptive immune response in the ‘CNA-devoid’ subgroup and a basal-specific chromosome 5 deletion-associated mitotic network. Our results provide a novel molecular stratification of the breast cancer population, derived from the impact of somatic CNAs on the transcriptome.

  14. Primary radiotherapy of breast cancer; Treatment results in locally advanced breast cancer and in operable patients selected by positive axillay apex biopsy

    Energy Technology Data Exchange (ETDEWEB)

    Borger, J.H.; Tienhoven, G. van; Passchier, D.H.; Hart, A.A.M.; Bartelink, H.; Dongen, J.A. van; Rutgers, E.J.T. (Nederlands Kanker Inst. ' Antoni van Leeuwenhoekhuis' , Amsterdam (Netherlands))

    1992-09-01

    To evaluate the efficacy of radiotherapy without surgery, treatment results in patients treated for locally advanced breast cancer (n=209) and those selected by positive axillary apex biopsy (n=289) in the period 1977 -1985 have been analysed retrospectively. Treatment consisted of primary irradiation to the breast and regional lymph nodes followed by a boost to the primary breast tumour and palpable regional disease to a mean normalised dose (NTD) of 64.7 Gy with a range of 33.4-93 Gy (2 Gy fractions, [alpha]/[beta] 5 Gy). Adjuvant systemic treatment was given in 30% of the locally advanced and in 40% of the apex positive patients. Thirty percent of the apex positive patients had an excisional biopsy of the breast tumour. Patients treated with adjuvant chemotherapy and patients irradiated to a NTD of 60 Gy or more had significantly better local control. For overall survival primary tumour size, clinical nodal size and age are independent prognostic factors. Patients irradiated to a NTD above 60 Gy had significantly better results. (author). 39 refs., 6 figs., 7 tabs.

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

    Energy Technology Data Exchange (ETDEWEB)

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

    2017-01-15

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

  16. Aggressive Multi-Visceral Pancreatic Resections for Locally Advanced Neuroendocrine Tumours. Is It Worth It?

    Directory of Open Access Journals (Sweden)

    Mohammed Abu Hilal

    2009-05-01

    Full Text Available Context Traditional surgical principles state that pancreatic resection should not be contemplated when malignancies arise in the pancreas and involve other organs. While this is logic for ductal adenocarcinoma and other tumours with aggressive biological behavior; for even large neuroendocrine tumours, aggressive multivisceral resection may achieve useful palliation and excellent survival. Design Case records were retrospectively analyzed. Patients and interventions Twelve consecutive patients (7 males, 5 females; median age 57 years, range: 37-79 years underwent multi-visceral en bloc resections for neuroendocrine tumour arising in the pancreas between 1994 and 2008. Results Three patients underwent pancreaticoduodenectomy; 9 patients had left sided pancreatic resections for neuroendocrine tumour of median diameter 9.5 cm ( 5-25 cm. They had a median of 3 (range: 1-4 additional organs resected. There were no post-operative deaths or late mortality with median follow up of 24 months. Five patients experienced a complication (major in 3 patients. Median disease free survival was not attained and 3 patients experienced recurrent disease mostly in the liver and may be candidates for further resection. Conclusion Aggressive multi-visceral resection for locally advanced neuroendocrine tumour involving the pancreas is technically feasible and in selected patients can be achieved with low mortality and acceptable morbidity, offering good disease free and overall survival. However this complex surgery should be only performed in specialist centers.

  17. 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

    2012-11-01

    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.

  18. 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

  19. 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...

  20. 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.

  1. Cooverexpression of EpCAM and c-myc genes in malignant breast tumours

    Indian Academy of Sciences (India)

    SAMIRA SADEGHI; ZOHREH HOJATI; HOSSEIN TABATABAEIAN

    2017-03-01

    The overexpression of epithelial cell adhesion molecule (EpCAM), a proto-oncogene, affects progression, treatment, and diagnosis of many adenocarcinomas. C-myc has been shown to be a downstream target of EpCAM and is also one of the most important proto-oncogenes routinely overexpressed in breast cancer. However, cooverexpression of EpCAM and c-mycgenes has not been investigated in breast cancer tissues, particularly in Iranian population. The aim of this study was to assess the expression of EpCAM and c-myc genes in malignant breast cancer tissues using reverse transcriptase-quantitative polymerase chain reaction (RT-qPCR) followed by analyses of the association between the outcomes. In this study, 122 fresh tissues, including 104 malignant and 18 benign samples, were disrupted by mortar and pestle, and then the RNA was isolated from the samples and converted to cDNA. The relative expression levels of EpCAM and c-myc genes were measured by2−ΔΔCt method using RT-qPCR. EpCAM protein level was also assessed in 66 cases using Western blot technique. UsingRT-qPCR method, our results showed that EpCAM was overexpressed in 48% of malignant and 11.1% of benign samples. Evaluating EpCAM protein overexpression in a portion of samples depicted the fully concordance rate between Western blot and RT-qPCR techniques. C-myc expression was first evaluated by RT-qPCR method, showing the overexpression rate of 39%and 28% in malignant and benign samples, respectively. These data were also quite concordant with the clinically available immunohistochemistry reports of the same samples studied in this study. Importantly, overexpression of EpCAM and c-myc was significantly associated and showed an agreement of 57.3%. This study demonstrated the cooverexpression of EpCAM and c-myc in breast tumours collected from breast cancer patients of the Iranian population. EpCAM and c-myc positive cases were significantly associated with reduced and enhanced risk of ER/PR positivity

  2. Combined doxorubicin and paclitaxel in advanced breast cancer

    DEFF Research Database (Denmark)

    Gehl, J; Boesgaard, M; Paaske, T

    1996-01-01

    BACKGROUND: Paclitaxel has shown activity in metastatic breast cancer, including anthracycline-resistant breast cancer. The efficacy, toxicity and optimal scheduling of the combination of the two drugs needs to be defined. PATIENTS AND METHODS: Thirty women with advanced breast cancer who had...

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

    LENUS (Irish Health Repository)

    Collins, AM

    2017-03-01

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

  5. 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.)

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

    Directory of Open Access Journals (Sweden)

    Wendy K Glenn

    Full Text Available 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 lactating women. For investigations based on in situ PCR we used 27 unselected archival formalin fixed breast cancer specimens and 18 unselected archival formalin fixed normal breast specimens from women who had breast reduction surgery. Thirteen of these fixed breast cancer specimens were ductal carcinoma in situ (dcis and 14 were predominantly invasive ductal carcinomas (idc. RESULTS: EBV sequences were identified in 68%, high risk HPV sequences in 50%, and MMTV sequences in 78% of DNA extracted from 50 invasive breast cancer specimens. These same viruses were identified in selected normal and breast cancer specimens by in situ PCR. Sequences from more than one viral type were identified in 72% of the same breast cancer specimens. Normal controls showed these viruses were also present in epithelial cells in human milk - EBV (35%, HPV, 20% and MMTV (32% of 40 milk samples from normal lactating women, with multiple viruses being identified in 13% of the same milk samples. CONCLUSIONS: We conclude that (i EBV, HPV and MMTV gene sequences are present and co-exist in many human breast cancers, (ii the presence of these viruses in breast cancer is associated with young age of diagnosis and possibly an increased grade of breast cancer.

  7. Palbociclib and Letrozole in Advanced Breast Cancer.

    Science.gov (United States)

    Finn, Richard S; Martin, Miguel; Rugo, Hope S; Jones, Stephen; Im, Seock-Ah; Gelmon, Karen; Harbeck, Nadia; Lipatov, Oleg N; Walshe, Janice M; Moulder, Stacy; Gauthier, Eric; Lu, Dongrui R; Randolph, Sophia; Diéras, Véronique; Slamon, Dennis J

    2016-11-17

    Background A phase 2 study showed that progression-free survival was longer with palbociclib plus letrozole than with letrozole alone in the initial treatment of postmenopausal women with estrogen-receptor (ER)-positive, human epidermal growth factor receptor 2 (HER2)-negative advanced breast cancer. We performed a phase 3 study that was designed to confirm and expand the efficacy and safety data for palbociclib plus letrozole for this indication. Methods In this double-blind study, we randomly assigned, in a 2:1 ratio, 666 postmenopausal women with ER-positive, HER2-negative breast cancer, who had not had prior treatment for advanced disease, to receive palbociclib plus letrozole or placebo plus letrozole. The primary end point was progression-free survival, as assessed by the investigators; secondary end points were overall survival, objective response, clinical benefit response, patient-reported outcomes, pharmacokinetic effects, and safety. Results The median progression-free survival was 24.8 months (95% confidence interval [CI], 22.1 to not estimable) in the palbociclib-letrozole group, as compared with 14.5 months (95% CI, 12.9 to 17.1) in the placebo-letrozole group (hazard ratio for disease progression or death, 0.58; 95% CI, 0.46 to 0.72; PPfizer; PALOMA-2 ClinicalTrials.gov number, NCT01740427 .).

  8. ApoA-I mimetic administration, but not increased apoA-I-containing HDL, inhibits tumour growth in a mouse model of inherited breast cancer

    Science.gov (United States)

    Cedó, Lídia; García-León, Annabel; Baila-Rueda, Lucía; Santos, David; Grijalva, Victor; Martínez-Cignoni, Melanie Raquel; Carbó, José M.; Metso, Jari; López-Vilaró, Laura; Zorzano, Antonio; Valledor, Annabel F.; Cenarro, Ana; Jauhiainen, Matti; Lerma, Enrique; Fogelman, Alan M.; Reddy, Srinivasa T.; Escolà-Gil, Joan Carles; Blanco-Vaca, Francisco

    2016-01-01

    Low levels of high-density lipoprotein cholesterol (HDLc) have been associated with breast cancer risk, but several epidemiologic studies have reported contradictory results with regard to the relationship between apolipoprotein (apo) A-I and breast cancer. We aimed to determine the effects of human apoA-I overexpression and administration of specific apoA-I mimetic peptide (D-4F) on tumour progression by using mammary tumour virus-polyoma middle T-antigen transgenic (PyMT) mice as a model of inherited breast cancer. Expression of human apoA-I in the mice did not affect tumour onset and growth in PyMT transgenic mice, despite an increase in the HDLc level. In contrast, D-4F treatment significantly increased tumour latency and inhibited the development of tumours. The effects of D-4F on tumour development were independent of 27-hydroxycholesterol. However, D-4F treatment reduced the plasma oxidized low-density lipoprotein (oxLDL) levels in mice and prevented oxLDL-mediated proliferative response in human breast adenocarcinoma MCF-7 cells. In conclusion, our study shows that D-4F, but not apoA-I-containing HDL, hinders tumour growth in mice with inherited breast cancer in association with a higher protection against LDL oxidative modification. PMID:27808249

  9. The utility of tumour markers in assessing the response to chemotherapy in advanced bladder cancer

    OpenAIRE

    Cook, A M; Huddart, R A; Jay, G; Norman, A.; Dearnaley, D. P.; Horwich, A

    2000-01-01

    In patients with advanced bladder cancer receiving chemotherapy, early assessment of response can avoid unnecessary toxicity. The aim of this study was to assess the role of tumour markers in monitoring response. Serum levels of one or more of markers β human chorionic gonadotrophin (βhCG), carcinoembryomic antigen (CEA), CA125 and CA19.9 were measured in 74 patients with advanced bladder cancer receiving chemotherapy from 1992 to 1997. Forty-three of 74 (58%) of patients had at least one rai...

  10. Breast Cancer Diagnosed During Pregnancy: Adapting Recent Advances in Breast Cancer Care for Pregnant Patients

    NARCIS (Netherlands)

    Loibl, S.; Schmidt, A.; Gentilini, O.; Kaufman, B.; Kuhl, C.; Denkert, C.; Minckwitz, G. von; Parokonnaya, A.; Stensheim, H.; Thomssen, C.; Calsteren, K. van; Poortmans, P.; Berveiller, P.; Markert, U.R.; Amant, F.

    2015-01-01

    Breast cancer during pregnancy (BCP), although rare, is becoming more common and treatment should be as similar as possible to that for nonpregnant young patients with breast cancer. A group of specialists convened to review current guidelines and provide guidance on how recent advances in breast ca

  11. Myoepithelial and epithelial-myoepithelial, mesenchymal and fibroepithelial breast lesions: updates from the WHO Classification of Tumours of the Breast 2012.

    Science.gov (United States)

    Tan, Puay Hoon; Ellis, Ian O

    2013-06-01

    In the 4th edition of the WHO Classification of Tumours of the Breast, myoepithelial lesions are retitled myoepithelial and epithelial-myoepithelial lesions in order to better reflect the dual participation of luminal and myoepithelial compartments in some key entities. Malignant myoepithelioma, described as a section within the chapter on myoepithelial lesions in the 3rd edition, is recognised in the 4th edition as part of metaplastic carcinoma. Adenomyoepithelioma with malignancy is categorised in terms of the cellular component undergoing malignant transformation. The list of antibodies that can be used for identifying myoepithelial cells is updated. Among mesenchymal lesions, new additions are nodular fasciitis and atypical vascular lesions, while the haemangiopericytoma is removed. The 3rd edition stated that pathological prediction of behaviour of phyllodes tumours is difficult in the individual case. In the 4th edition, some progress has been made in prioritisation and weighting of histological parameters that can potentially estimate probability of recurrence. The WHO Working Group advocates leaning towards a diagnosis of fibroadenoma in cases where there is histological uncertainty in distinction from a benign phyllodes tumour, or adopting the neutral term 'benign fibroepithelial neoplasm', as the clinical behaviour of fibroadenoma overlaps with that of benign phyllodes tumour. The 3rd edition terminology of 'periductal stromal sarcoma' is revised to 'periductal stromal tumour', akin to the widespread consensus to avoid the use of the term 'cystosarcoma' in the context of phyllodes tumours.

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

    Energy Technology Data Exchange (ETDEWEB)

    Reubi, Jean Claude; Gugger, Mathias; Waser, Beatrice [Division of Cell Biology and Experimental Cancer Research, Institute of Pathology, University of Berne (Switzerland)

    2002-07-01

    Breast cancers can express different types of peptide receptors such as somatostatin, vasoactive intestinal peptide (VIP), gastrin-releasing peptide (GRP) and NPY(Y{sub 1}) 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, VPAC{sub 1}, GRP and NPY(Y{sub 1}) receptors using in vitro receptor autoradiography on successive tissue sections with {sup 125}I-[Tyr{sup 3}]-octreotide, {sup 125}I-VIP, {sup 125}I-[Tyr{sup 4}]-bombesin and {sup 125}I-[Leu{sup 31},Pro{sup 34}]-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 (<2,000 dpm/mg tissue). In the group with high receptor density, 50 of the 68 tumours (74%) expressed GRP receptors, 45 (66%) expressed NPY(Y{sub 1}) receptors, 25 (37%) expressed VPAC{sub 1} 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(Y{sub 1}) receptors, 4,337{+-}528 dpm/mg for somatostatin receptors and 3,437{+-}306 dpm/mg for VPAC{sub 1} receptors. It is of note that tumours expressing NPY(Y{sub 1}) 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 Y{sub 1} analogues should allow targeting of breast carcinomas and their lymph node metastases for in vivo peptide receptor scintigraphy and radiotherapy

  13. Advanced Breast Cancer as Indicator of Quality Mammography

    Science.gov (United States)

    Gaona, Enrique

    2003-09-01

    Breast cancer is the most frequently diagnosed cancer and is the second leading cause of cancer death among women in the Mexican Republic. Mammography is the more important screening tool for detecting early breast cancer. Screening mammography involves taking x-rays from two views from each breast, typically from above (cranial-caudal view, CC) and from an oblique or angled view (mediolateral-oblique, MLO). The purpose of this study was to carry out an exploratory survey of the issue of patients with advanced breast cancer who have had a screening mammography. A general result of the survey is that 22.5% of all patients (102) with advanced breast cancer that participated in the study had previous screening mammography. But we should consider that 10% of breast cancers are not detected by mammography. Only 70% of the family doctors prescribed a diagnostic mammography when the first symptoms were diagnosed.

  14. 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

  15. 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.

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

    Energy Technology Data Exchange (ETDEWEB)

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

    1997-09-01

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

  17. 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

    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...... and predictive marker in advanced breast cancer patients receiving docetaxel (D) or gemcitabine plus docetaxel (GD). METHODS: Patients with locally advanced or metastatic breast cancer who were assigned to D or GD by participation in a randomized phase III trial were included in the study. Assessment of TIMP-1...... 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...

  18. Liposomal Nanoparticles Carrying anti-IL6R Antibody to the Tumour Microenvironment Inhibit Metastasis in Two Molecular Subtypes of Breast Cancer Mouse Models

    Science.gov (United States)

    Guo, Chunlei; Chen, Yanan; Gao, Wenjuan; Chang, Antao; Ye, Yujie; Shen, Wenzhi; Luo, Yunping; Yang, Shengyong; Sun, Peiqing; Xiang, Rong; Li, Na

    2017-01-01

    Tumour microenvironment (TME) contributes significantly towards potentiating the stemness and metastasis properties of cancer cells. IL6-Stat3 is one of the important cell signaling pathways in mediating the communication between tumour and immune cells. Here, we have systematically developed a novel anti-CD44 antibody-mediated liposomal nanoparticle delivery system loaded with anti-IL6R antibody, which could specifically target the TME of CD44+ breast cancer cells in different mouse models for triple negative and luminal breast cancer. This nanoparticle had an enhanced and specific tumour targeting efficacy with dramatic anti-tumour metastasis effects in syngeneic BALB/c mice bearing 4T1 cells as was in the syngeneic MMTV-PyMT mice. It inhibited IL6R-Stat3 signaling and moderated the TME, characterized by the reduced expression of genes encoding Stat3, Sox2, VEGFA, MMP-9 and CD206 in the breast tissues. Furthermore, this nanoparticle reduced the subgroups of Sox2+ and CD206+ cells in the lung metastatic foci, demonstrating its inhibitory effect on the lung metastatic niche for breast cancer stem cells. Taken together, the CD44 targeted liposomal nanoparticles encapsulating anti-IL6R antibody achieved a significant effect to inhibit the metastasis of breast cancer in different molecular subtypes of breast cancer mouse models. Our results shed light on the application of nanoparticle mediated cancer immune-therapy through targeting TME. PMID:28255366

  19. 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.

  20. 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.

  1. ERCC1 and telomere status in breast tumours treated with neoadjuvant chemotherapy and their association with patient prognosis

    Science.gov (United States)

    Gay‐Bellile, Mathilde; Romero, Pierre; Cayre, Anne; Véronèse, Lauren; Privat, Maud; Singh, Shalini; Combes, Patricia; Kwiatkowski, Fabrice; Abrial, Catherine; Bignon, Yves‐Jean; Vago, Philippe; Penault‐Llorca, Frédérique

    2016-01-01

    Abstract Dysfunctional telomeres and DNA damage repair (DDR) play important roles in cancer progression. Studies have reported correlations between these factors and tumour aggressiveness and clinical outcome in breast cancer. We studied the characteristics of telomeres and expression of ERCC1, a protein involved in a number of DNA repair pathways and in telomere homeostasis, to assess their prognostic value, alone or in combination, in 90 residual breast tumours after treatment with neoadjuvant chemotherapy (NCT). ERCC1 status was investigated at different molecular levels (protein and gene expression and gene copy‐number variations) by immunohistochemistry, qRT‐PCR and quantitative multiplex fluorescent‐PCR (QMF‐PCR). A comprehensive analysis of telomere characteristics was performed using qPCR for telomere length and qRT‐PCR for telomerase (hTERT), tankyrase 1 (TNKS) and shelterin complex (TRF1, TRF2, POT1, TPP1, RAP1 and TIN2) gene expression. Short telomeres, high hTERT and TNKS expression and low ERCC1 protein expression were independently associated with worse survival outcome. Interestingly, ERCC1 gains and losses correlated with worse disease‐free (p = 0.026) and overall (p = 0.043) survival as compared to survival of patients with normal gene copy‐numbers. Unsupervised hierarchical clustering of all ERCC1 and telomere parameters identified four subgroups with distinct prognosis. In particular, a cluster combining low ERCC1, ERCC1 gene alterations, dysfunctional telomeres and high hTERT and a cluster with high TNKS and shelterin expression correlated with poor disease‐free (HR= 5.41, p= 0.0044) and overall survival (HR= 6.01, p= 0.0023) irrespective of tumour stage and grade. This comprehensive study demonstrates that telomere dysfunction and DDR can contribute synergistically to tumour progression and chemoresistance. These parameters are predictors of clinical outcome in breast cancer patients treated with NCT and could be useful

  2. 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.

  3. Phase i and pharmacological study of pazopanib in combination with oral topotecan in patients with advanced solid tumours

    NARCIS (Netherlands)

    Kerklaan, B. Milojkovic; Lolkema, M. P J; Devriese, L. A.; Voest, E. E.; Nol-Boekel, A.; Mergui-Roelvink, M.; Langenberg, M.; Mykulowycz, K.; Stoebenau, J.; Lane, S.; Legenne, P.; Wissel, P.; Smith, D. A.; Giantonio, B. J.; Schellens, J. H M; Witteveen, P. O.

    2015-01-01

    Background: This phase I study evaluated the safety, tolerability, maximum tolerated dose (MTD) and pharmacokinetics of two dosing schedules of oral topotecan in combination with pazopanib in patients with advanced solid tumours. Methods: Stage I of this study was to determine whether there was an i

  4. 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;

    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...

  5. 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.

  6. Up-regulated Proteins in the Fluid Bathing the Tumour Cell Microenvironment as Potential Serological Markers for Early Detection of Cancer of the Breast

    DEFF Research Database (Denmark)

    Gromov, Pavel; Gromova, Irina; Bunkenborg, Jakob

    2010-01-01

    -based proteomics in combination with mass spectrometry and immunohistochemistry (IHC) of the tumour interstitial fluids (TIF) and normal interstitial fluids (NIF) collected from 69 prospective breast cancer patients. The goal of this study was to identify abundant cancer up-regulated proteins that are externalised...

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

    DEFF Research Database (Denmark)

    Gromov, Pavel; Gromova, Irina; Bunkenborg, Jakob

    2010-01-01

    -based proteomics in combination with mass spectrometry and immunohistochemistry (IHC) of the tumour interstitial fluids (TIF) and normal interstitial fluids (NIF) collected from 69 prospective breast cancer patients. The goal of this study was to identify abundant cancer up-regulated proteins that are externalised...

  8. 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...

  9. An autopsy case of acute cor pulmonale and paradoxical systemic embolism due to tumour cell microemboli in a patient with breast cancer.

    Science.gov (United States)

    Uga, Sayuri; Ikeda, Shuntaro; Matsukage, Sho-ichi; Hamada, Mareomi

    2012-09-30

    A 62-year-old woman was admitted to our hospital because of severe respiratory distress. Diagnostic imaging studies suggested the existence of inexplicable cor pulmonale. Although we immediately sought the aetiology of her severe condition, she died suddenly on the fourth day after admission. Postmortem autopsy revealed tumour cell microemboli in the small pulmonary arteries. In addition, tumour cell embolisation identical to that in primary breast cancer cells was also observed in microvessels in systemic multiple organs, such as the liver, brain, kidneys, spleen, uterus, bone marrow and adrenal glands-with simultaneous findings of peripheral infarction. Systemic tumour cell embolism mediated through the patent foramen ovale superimposed on pulmonary tumour cell emboli (PTCE) is considered to be the mechanism underlying inexplicable cor pulmonale. The rapid aggravation of her condition terminated in death.

  10. 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

    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...... and predictive marker in advanced breast cancer patients receiving docetaxel (D) or gemcitabine plus docetaxel (GD). METHODS: Patients with locally advanced or metastatic breast cancer who were assigned to D or GD by participation in a randomized phase III trial were included in the study. Assessment of TIMP-1...... 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...

  11. Primary radiotherapy after tumour excision as an alternative to mastectomy for early breast cancer

    Energy Technology Data Exchange (ETDEWEB)

    Browde, S.; Nissenbaum, M.M. (University of the Witwatersrand, Johannesburg (South Africa))

    1983-09-28

    A conservative approach to the management of breast cancer is gaining acceptance. The evidence from many retrospective and prospective studies indicates that breast-preserving surgery and radiation therapy give results equal to those of mastectomy. Relapse affecting the breast alone has been shown not to be detrimental to survival, while the psychological benefits to the patients have been gratifying. A prospective study of early breast cancer treated by conservative surgery and radiation was commenced at the Johannesburg Hospital in 1980. The results in 57 patients are reported. So far there have been 2 cases of local recurrence. In the majority of cases satisfactory cosmetic results were achieved. It is considered that lumpectomy with axillary dissection to establish nodal status followed by irradiation is the treatment of choice for stage l and ll carcinoma of the breast.

  12. 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.

  13. Doxorubicin plus paclitaxel in advanced breast cancer

    DEFF Research Database (Denmark)

    Dombernowsky, P; Boesgaard, M; Andersen, E

    1997-01-01

    between administration of a short infusion of doxorubicin followed by a 3-hour infusion of paclitaxel was evaluated. Included were patients with metastatic breast cancer, who received doxorubicin 50 mg/m2 followed by paclitaxel 200 mg/m2 at intervals of 30 minutes, 4 hours, and 24 hours every 3 weeks......The combination of bolus doxorubicin and paclitaxel (Taxol; Bristol-Myers Squibb Company, Princeton, NJ) as a 3-hour infusion is highly active in patients with metastatic breast cancer, but it has considerable cardiotoxicity. In this ongoing study, the potential effect of increasing the interval....... As of February 1997, 34 patients have been enrolled, two patients are too early to evaluate, and 13 are continuing treatment. The preliminary response rate is 69% (95% confidence interval, 50% to 84%), ranging from 60% to 80% within the three schedules. The main toxicities consisted of grade 3/4 neutropenia...

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

    DEFF Research Database (Denmark)

    Paulsen, Ida Felbo; Chakera, A H; Drejøe, Jennifer Berg

    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 M...

  15. 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.

  16. Breast cancer stem cells: current advances and clinical implications.

    Science.gov (United States)

    Luo, Ming; Clouthier, Shawn G; Deol, Yadwinder; Liu, Suling; Nagrath, Sunitha; Azizi, Ebrahim; Wicha, Max S

    2015-01-01

    There is substantial evidence that many cancers, including breast cancer, are driven by a population of cells that display stem cell properties. These cells, termed cancer stem cells (CSCs) or tumor initiating cells, not only drive tumor initiation and growth but also mediate tumor metastasis and therapeutic resistance. In this chapter, we summarize current advances in CSC research with a major focus on breast CSCs (BCSCs). We review the prevailing methods to isolate and characterize BCSCs and recent evidence documenting their cellular origins and phenotypic plasticity that enables them to transition between mesenchymal and epithelial-like states. We describe in vitro and clinical evidence that these cells mediate metastasis and treatment resistance in breast cancer, the development of novel strategies to isolate circulating tumor cells (CTCs) that contain CSCs and the use of patient-derived xenograft (PDX) models in preclinical breast cancer research. Lastly, we highlight several signaling pathways that regulate BCSC self-renewal and describe clinical implications of targeting these cells for breast cancer treatment. The development of strategies to effectively target BCSCs has the potential to significantly improve the outcomes for patients with breast cancer.

  17. Targeted treatment of advanced and metastatic breast cancer with lapatinib

    Directory of Open Access Journals (Sweden)

    Brendan Corkery

    2008-09-01

    Full Text Available Brendan Corkery1,2, Norma O’Donovan2, John Crown1,21St. Vincent’s University Hospital, Dublin, Ireland; 2National Institute for Cellular Biotechnology, Dublin City University, Dublin, IrelandAbstract: Improved molecular understanding of breast cancer in recent years has led to the discovery of important drug targets such as HER-2 and EGFR. Lapatinib is a potent dual inhibitor of HER-2 and EGFR. Preclinical and phase I studies have shown activity with lapatinib in a number of cancers, including breast cancer, and the drug is well tolerated. The main known drug interactions are with paclitaxel and irinotecan. The most significant side-effects of lapatinib are diarrhea and adverse skin events. Rates of cardiotoxicity compare favorably with trastuzumab, a monoclonal antibody against HER-2. This paper focuses on lapatinib in advanced and metastatic breast cancer, which remains an important therapeutic challenge. Phase II and III studies show activity as monotherapy, and in combination with chemotherapy or hormonal agents. Results from these studies suggest that the main benefit from lapatinib is in the HER-2 positive breast cancer population. Combinations of lapatinib and trastuzumab are also being studied and show encouraging results, particularly in trastuzumab-refractory metastatic breast cancer. Lapatinib may have a specific role in treating HER-2 positive CNS metastases. The role of lapatinib as neoadjuvant therapy and in early breast cancer is also being evaluated.Keywords: HER-2, EGFR, erbB, lapatinib, Tykerb®, tyrosine kinase

  18. Advances in Medical Management of Early Stage and Advanced Breast Cancer: 2015.

    Science.gov (United States)

    Witherby, Sabrina; Rizack, Tina; Sakr, Bachir J; Legare, Robert D; Sikov, William M

    2016-01-01

    Standard management of early stage and advanced breast cancer has been improved over the past few years by knowledge gained about the biology of the disease, results from a number of eagerly anticipated clinical trials and the development of novel agents that offer our patients options for improved outcomes or reduced toxicity or both. This review highlights recent major developments affecting the systemic therapy of breast cancer, broken down by clinically relevant patient subgroups and disease stage, and briefly discusses some of the ongoing controversies in the treatment of breast cancer and promising therapies on the horizon.

  19. 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.)

  20. Bony metastases from breast cancer - a study of foetal antigen 2 as a blood tumour marker

    Directory of Open Access Journals (Sweden)

    Iles Ray K

    2010-05-01

    Full Text Available Abstract Background Foetal antigen 2 (FA-2, first isolated in the amniotic fluid, was shown to be the circulating form of the aminopropeptide of the alpha 1 chain of procollagen type I. Serum concentrations of FA-2 appeared to be elevated in a number of disorders of bone metabolism. This paper is the first report of its role as a marker of bone metabolism in metastatic breast cancer. Methods Serum FA-2 concentrations were measured by radioimmunoassay in 153 women with different stages of breast cancer and in 34 normal controls. Results Serum FA-2 was significantly elevated in women with bony metastases (p Conclusions FA-2 is a promising blood marker of bone metabolism. Further studies to delineate its role in the diagnosis and management of bony metastases from breast cancer are required.

  1. Clinical trials update: Medical management of advanced breast cancer.

    Science.gov (United States)

    Major, Maureen A

    2003-12-01

    Selection of treatment for metastatic breast cancer depends on several factors: the status of estrogen receptors or progesterone receptors on breast cancer cells and the expression levels of human epidermal growth factor receptor-2. The presence of estrogen or progesterone receptors typically indicates slower-growing tumors that may be amenable to hormonal manipulation, which provides significant disease control while offering a better toxicity profile than conventional chemotherapy. The understanding of hormonal therapies in patients with postmenopausal metastatic breast cancer has advanced greatly in the past several decades. Aromatase inhibitors, although used initially as second-line therapy, recently have proved to be as effective as tamoxifen, if not superior to it, as first-line therapy for metastatic breast cancer. New data also suggest that letrozole provides significantly better objective responses than anastrozole as second-line therapy. Exemestane, a steroidal aromatase inhibitor, is an effective third-line therapy. Fulvestrant, an estrogen receptor antagonist with no known agonist effect, provides a new option for hormonal therapy. For patients with metastatic breast cancer and overexpression of human epidermal growth factor receptor-2 on tumor cells, the monoclonal antibody trastuzumab is the preferred option, either in combination with paclitaxel as first-line treatment, or as a single agent for second-line therapy. By extending the sequence of hormonal therapy, disease progression and the need for chemotherapy may be significantly delayed, potentially extending patient survival rates and improving quality of life.

  2. Results of chest wall resection for recurrent or locally advanced breast malignancies.

    Science.gov (United States)

    Veronesi, Giulia; Scanagatta, Paolo; Goldhirsch, Aron; Rietjens, Mario; Colleoni, Marco; Pelosi, Giuseppe; Spaggiari, Lorenzo

    2007-06-01

    Between 1998 and 2003 we observed 15 women who underwent full thickness chest wall resection (FTCWR) followed by plastic reconstruction for locally recurrent or primary breast cancer. Preoperative symptoms were: pain (5 patients), malodorous ulceration (3 patients), presence of tumour mass (4 patients) and thoracic deformity (2 patients). One patient was asymptomatic. Surgery was partial sternectomy with rib resection in 9 patients, rib resection alone in 5, and total sternectomy in one. No perioperative mortality or major morbidity occurred; minor complications occurred in 3 patients (20%). Five of the six surviving patients reported a positive overall outcome in a telephonic interview. Median overall and disease-free survival were 23.4 and 17.5 months, respectively. In conclusion, FTCWR is a safe procedure with low morbidity and mortality that can provide good symptoms palliation in patients with locally advanced breast malignancies, so it should be considered more often by interdisciplinary care providers in those patients who fail to respond to classic multimodality treatment.

  3. TU-EF-207-00: Advances in Breast Imaging

    Energy Technology Data Exchange (ETDEWEB)

    NONE

    2015-06-15

    Breast imaging technology is advancing on several fronts. In digital mammography, the major technological trend has been on optimization of approaches for performing combined mammography and tomosynthesis using the same system. In parallel, photon-counting slot-scan mammography is now in clinical use and more efforts are directed towards further development of this approach for spectral imaging. Spectral imaging refers to simultaneous acquisition of two or more energy-windowed images. Depending on the detector and associated electronics, there are a number of ways this can be accomplished. Spectral mammography using photon-counting detectors can suppress electronic noise and importantly, it enables decomposition of the image into various material compositions of interest facilitating quantitative imaging. Spectral imaging can be particularly important in intravenously injected contrast mammography and eventually tomosynthesis. The various approaches and applications of spectral mammography are discussed. Digital breast tomosynthesis relies on the mechanical movement of the x-ray tube to acquire a number of projections in a predefined arc, typically from 9 to 25 projections over a scan angle of +/−7.5 to 25 degrees depending on the particular system. The mechanical x-ray tube motion requires relatively long acquisition time, typically between 3.7 to 25 seconds depending on the system. Moreover, mechanical scanning may have an effect on the spatial resolution due to internal x-ray filament or external mechanical vibrations. New x-ray source arrays have been developed and they are aimed at replacing the scanned x-ray tube for improved acquisition time and potentially for higher spatial resolution. The potential advantages and challenges of this approach are described. Combination of digital mammography and tomosynthesis in a single system places increased demands on certain functional aspects of the detector and overall performance, particularly in the tomosynthesis

  4. Treatment algorithm in 2014 for advanced non-small cell lung cancer: therapy selection by tumour histology and molecular biology.

    Science.gov (United States)

    Manegold, Christian

    2014-09-01

    The availability of antineoplastic monoclonal antibodies, small molecules and newer cytotoxics such as pemetrexed, the EGFR-tyrosine kinase inhibitors erlotinib, gefitinib, afatinib as well as the anti-angiogenic bevacizumab and the ALK-inhibitor crizotinib has recently changes the treatment algorithm of advanced non-small cell lung cancer. Decision making in 2014 is characterized by customizing therapy, by selecting a specific therapeutic regimen based on the histotype and the genotype of the tumour. This refers to first-line induction therapy and maintenance therapy as well, but also to subsequent lines of therapy since anti-neoplastic drugs and regimens used upfront clinically influence the selection of agents/regimes considered for second-/third-line treatment. Consequently, therapy customization through tumour histology and molecular markers has significantly influenced the work of pathologists around the globe and the process of obtaining an extended therapeutically relevant tumour diagnosis. Not only histological sub-typing became standard but molecular information is also considered of increasing importance for treatment selection. Routine molecular testing in certified laboratories must be established, and the diagnostic process should ideally be performed under the guidance of evidence based recommendation. The process of investigating and implementing medical targeting in lung cancer therefore, requires advanced diagnostic techniques and expertise and because of its large dimension is costly and influenced by the limitation of financial and clinical resources.

  5. Advance care planning in patients with primary malignant brain tumours: a systematic review

    Directory of Open Access Journals (Sweden)

    Krystal Song

    2016-10-01

    Full Text Available Advance care planning (ACP is a process of reflection and communication of a person’s future health care preferences, and has been shown to improve end-of-life care for patients. The aim of this systematic review is to present an evidence-based overview of ACP in patients with primary malignant brain tumours (pmBT. A comprehensive literature search was conducted using medical and health science electronic databases (PubMed, Cochrane, Embase, MEDLINE, ProQuest, Social Care Online, Scopus and Web of Science up to July 2016. Manual search of bibliographies of articles and grey literature search were also conducted. Two independent reviewers selected studies, extracted data and assessed the methodologic quality of the studies using the Critical Appraisal Skills Program’s appraisal tools. All studies were included irrespective of the study design. A meta-analysis was not possible due to heterogeneity amongst included studies; therefore, a narrative analysis was performed for best evidence synthesis. Overall, 19 studies were included (1 RCT, 17 cohort studies, 1 qualitative study with 4686 participants. All studies scored low to moderate on the methodological quality assessment, implying high risk of bias. A single RCT evaluating a video decision support tool in facilitating ACP in pmBT patients showed a beneficial effect in promoting comfort care and gaining confidence in decision–making. However, the effect of the intervention on quality of life and care at the end-of-life were unclear. There was a low rate of use of ACP discussions at the end-of-life. Advance Directive completion rates and place of death varied between different studies. Positive effects of ACP included lower hospital readmission rates, and intensive care unit utilization. None of the studies assessed mortality outcomes associated with ACP. In conclusion, this review found some beneficial effects of ACP in pmBT. The literature still remains limited in this area, with lack of

  6. The prognostic value of tumour-stroma ratio in triple-negative breast cancer

    NARCIS (Netherlands)

    Moorman, A.M.; Vink, R.; Heijmans, H.J.; Palen, van der J.A.M.; Kouwenhoven, E.A.

    2012-01-01

    Background Triple-negative cancer constitutes one of the most challenging groups of breast cancer given its aggressive clinical behaviour, poor outcome and lack of targeted therapy. Until now, profiling techniques have not been able to distinguish between patients with a good and poor outcome. Recen

  7. Digital Mammography Imaging: Breast Tomosynthesis and Advanced Applications

    Science.gov (United States)

    Helvie, Mark A.

    2011-01-01

    Synopsis This article discusses recent developments in advanced derivative technologies associated with digital mammography. Digital breast tomosynthesis – its principles, development, and early clinical trials are reviewed. Contrast enhanced digital mammography and combined imaging systems with digital mammography and ultrasound are also discussed. Although all these methods are currently research programs, they hold promise for improving cancer detection and characterization if early results are confirmed by clinical trials. PMID:20868894

  8. The sodium channel β1 subunit mediates outgrowth of neurite-like processes on breast cancer cells and promotes tumour growth and metastasis.

    Science.gov (United States)

    Nelson, Michaela; Millican-Slater, Rebecca; Forrest, Lorna C; Brackenbury, William J

    2014-11-15

    Voltage-gated Na(+) channels (VGSCs) are heteromeric proteins composed of pore-forming α subunits and smaller β subunits. The β subunits are multifunctional channel modulators and are members of the immunoglobulin superfamily of cell adhesion molecules (CAMs). β1, encoded by SCN1B, is best characterized in the central nervous system (CNS), where it plays a critical role in regulating electrical excitability, neurite outgrowth and migration during development. β1 is also expressed in breast cancer (BCa) cell lines, where it regulates adhesion and migration in vitro. In the present study, we found that SCN1B mRNA/β1 protein were up-regulated in BCa specimens, compared with normal breast tissue. β1 upregulation substantially increased tumour growth and metastasis in a xenograft model of BCa. β1 over-expression also increased vascularization and reduced apoptosis in the primary tumours, and β1 over-expressing tumour cells had an elongate morphology. In vitro, β1 potentiated outgrowth of processes from BCa cells co-cultured with fibroblasts, via trans-homophilic adhesion. β1-mediated process outgrowth in BCa cells required the presence and activity of fyn kinase, and Na(+) current, thus replicating the mechanism by which β1 regulates neurite outgrowth in CNS neurons. We conclude that when present in breast tumours, β1 enhances pathological growth and cellular dissemination. This study is the first demonstration of a functional role for β1 in tumour growth and metastasis in vivo. We propose that β1 warrants further study as a potential biomarker and targeting β1-mediated adhesion interactions may have value as a novel anti-cancer therapy.

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

    Energy Technology Data Exchange (ETDEWEB)

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

    2012-11-15

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

  10. 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.

  11. Introduction to 'A multitargeted approach: Clinical advances in the treatment of solid tumours'

    NARCIS (Netherlands)

    D.J. George (Daniel); J. Verweij (Jaap)

    2007-01-01

    textabstractAlthough single-target agents have been shown to improve patient outcomes in certain tumour types, drug resistance often occurs due to salvage pathways that compensate for the inhibited signalling pathway. Simultaneous inhibition of individual target receptors along multiple pathways has

  12. 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.

  13. C-erbB-2 onco-protein expression in breast cancer: relationship to tumour characteristics and short-term survival in Universiti Kebansaan Malaysia Medical Centre.

    Science.gov (United States)

    Sharifah, N A; Lee, B R; Clarence-Ko, C H; Tan, G C; Shiran, M S; Naqiyah, I; Rohaizak, M; Fuad, I; Tamil, A M

    2008-01-01

    Breast cancer is the commonest cancer affecting females in Malaysia, contributing 31% of all newly diagnosed cases amongst Malaysian women. The present retrospective cohort study evaluated the relationship between cerbB- 2 onco-protein overexpression with various tumour characteristics and survival rate of breast cancer patients treated at the Universiti Kebangsaan Malaysia Medical Centre (UKMMC) between 1996-2000. CerbB- 2 oncoprotein overexpression was determined by immunohistochemistry (IHC) and tumors showing 2+ positivity were verified by Fluorescence In Situ Hybridization (FISH). One hundred and seventy two patients were eligible for the study with a short-term follow-up (median) of 5.1 years. C-erbB-2 oncoprotein overexpression correlated with lymph node positivity, oestrogen receptor (ER) and progesterone receptor (PR) negativity. Univariate analyses showed shorter disease free survival (DFS) and overall survival (OS) in patients with cerbB- 2 oncoprotein overexpression, Malay ethnicity, higher tumour grade, lymph node positivity, ER and PR negativity. In a subgroup of patients with c-erbB-2 oncoprotein overexpression, a shorter OS was observed in those with lymph node positivity, ER and PR negativity. In multivariate prognostic analysis, lymph node status, ER status and tumour grading were the strongest independent prognostic factors for both OS and DFS. However, c-erbB-2 status was not a significantly independent prognostic factor, even in subsets with lymph node positive or negative group. C-erbB-2 oncoprotein overexpression correlated well with lymph node status, ER and PR. Shorter OS and DFS were significantly observed in patients with c-erbB-2 oncoprotein overexpression. Lymph node status, ER status and tumour grading were the only three independent prognostic factors for OS and DFS in this study. Although c-erbB-2 expression is obviously important from a biological standpoint, multivariate analysis showed that it is not an independent prognostic

  14. The effects of renal variation upon measurements of perfusion and leakage volume in breast tumours

    Science.gov (United States)

    Ahearn, T. S.; Staff, R. T.; Redpath, T. W.; Semple, S. I. K.

    2004-05-01

    Dynamic contrast enhanced MRI (DCE-MRI) and pharmacokinetic models have been used to measure tumour permeability (Ktrans) and leakage volume (ve) in numerous studies. The construction of pharmacokinetic models describing such tissue properties relies on defining the blood plasma concentration of contrast agent with respect to time (Cp(t)). When direct measurement is not possible a bi-exponential decay has been applied using data from healthy volunteers. This work investigates, by simulation, the magnitude of errors resulting from this definition with respect to normal variation in renal function and for cases with renal impairment. Errors up to 23% in ve and 28% in Ktrans were found for the normal simulations, and 67% in ve and 61% in Ktrans for the impaired simulations. If this bi-exponential curve is used as an input function to the generalized kinetic model and used in oncology, estimates of tissue permeability and leakage volume will possess large errors due to variation in Cp(t) curves between subjects.

  15. 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

  16. Expression of Multidrug Resistance-Associated Markers, Their Relation to Quantitative Pathologic Tumour Characteristics and Prognosis in Advanced Ovarian Cancer

    Directory of Open Access Journals (Sweden)

    Mariël Brinkhuis

    2002-01-01

    Full Text Available Mean nuclear area has been consistently shown by different researchers to be a strong and independent prognostic factor in advanced ovarian carcinoma. However, the biological background of the prognostic value of nuclear area remains unclear. Others have found that the multidrug‐resistance (MDR related protein LRP has strong prognostic value. In the present study we have analysed whether the mean nuclear area and LRP are related in tumour tissue of the ovary obtained at the debulking operation before the administration of chemotherapy in 40 patients. The mitotic activity index, volume percentage epithelium, standard deviation of nuclear area and the other MDR‐related proteins P‐glycoprotein (JSB‐1, MRK‐16 and MRP have been investigated additionally for correlations and prognostic value. No correlations were found between the morphometrical features and MDR‐related proteins. Mean nuclear area tended to be larger in LRP positive tumours, but the correlation was not significant. In multivariate analysis LRP‐protein expression and mean nuclear area had independent prognostic value. Further studies are required to elucidate the biological background of the strong prognostic value of mean nuclear area in advanced ovarian cancer.

  17. The novel desmopressin analogue [V4Q5]dDAVP inhibits angiogenesis, tumour growth and metastases in vasopressin type 2 receptor-expressing breast cancer models

    Science.gov (United States)

    GARONA, JUAN; PIFANO, MARINA; ORLANDO, ULISES D.; PASTRIAN, MARIA B.; IANNUCCI, NANCY B.; ORTEGA, HUGO H.; PODESTA, ERNESTO J.; GOMEZ, DANIEL E.; RIPOLL, GISELLE V.; ALONSO, DANIEL F.

    2015-01-01

    Desmopressin (dDAVP) is a safe haemostatic agent with previously reported antitumour activity. It acts as a selective agonist for the V2 vasopressin membrane receptor (V2r) present on tumour cells and microvasculature. The purpose of this study was to evaluate the novel peptide derivative [V4Q5]dDAVP in V2r-expressing preclinical mouse models of breast cancer. We assessed antitumour effects of [V4Q5]dDAVP using human MCF-7 and MDA-MB-231 breast carcinoma cells, as well as the highly metastatic mouse F3II cell line. Effect on in vitro cancer cell growth was evaluated by cell proliferation and clonogenic assays. Cell cycle distribution was analysed by flow cytometry. In order to study the effect of intravenously administered [V4Q5]dDAVP on tumour growth and angiogenesis, breast cancer xenografts were generated in athymic mice. F3II cells were injected into syngeneic mice to evaluate the effect of [V4Q5]dDAVP on spontaneous and experimental metastatic spread. In vitro cytostatic effects of [V4Q5]dDAVP against breast cancer cells were greater than those of dDAVP, and associated with V2r-activated signal transduction and partial cell cycle arrest. In MDA-MB-231 xenografts, [V4Q5]dDAVP (0.3 μg/kg, thrice a week) reduced tumour growth and angiogenesis. Treatment of F3II mammary tumour-bearing immunocompetent mice resulted in complete inhibition of metastatic progression. [V4Q5]dDAVP also displayed greater antimetastatic efficacy than dDAVP on experimental lung colonisation by F3II cells. The novel analogue was well tolerated in preliminary acute toxicology studies, at doses ≥300-fold above that required for anti-angiogenic/antimetastatic effects. Our data establish the preclinical activity of [V4Q5]dDAVP in aggressive breast cancer, providing the rationale for further clinical trials. PMID:25846632

  18. 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

    ) 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...... the treatment. In conclusion, the strategy for p53-DC vaccination seems safe and without toxicity. Furthermore, indications of both immunologic and clinical effect were found in heavily pretreated patients with advanced breast cancer. An independent clinical effect of repeated administration of DCs and IL-2 can......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...

  19. Survival of breast cancer patients with synchronous or metachronous central nervous system metastases

    NARCIS (Netherlands)

    Ho, V.K.; Gijtenbeek, J.M.M.; Brandsma, D.; Beerepoot, L.V.; Sonke, G.S.; Loo, M. te

    2015-01-01

    BACKGROUND: Central nervous system (CNS) metastases represent a devastating complication for advanced breast cancer patients. This observational study examines the influence of patient, tumour and treatment characteristics on overall survival after synchronous or metachronous CNS metastases. METHODS

  20. PAM50 breast cancer intrinsic subtypes and effect of gemcitabine in advanced breast cancer patients

    DEFF Research Database (Denmark)

    Jørgensen, Charlotte Levin Tykjær; Nielsen, Torsten O; Bjerre, Karsten D

    2014-01-01

    chemotherapy were analyzed by the Kaplan-Meier method, and Cox proportional hazards regression models. Data analysis was performed independently by the Danish Breast Cancer Cooperative Group (DBCG) statistical core and all statistical tests were two-sided. RESULTS: RNA from 270 patients was evaluable; 84...... by NanoString nCounter. Statistical analyses were prespecified as a formal prospective-retrospective clinical trial correlative study. Using time to progression (TTP) as primary endpoint, overall survival (OS) and response rate as secondary endpoints, relationships between subtypes and outcome after......: A significantly improved and clinically important prolongation of survival was seen from the addition of gemcitabine to docetaxel in advanced basal-like breast cancer patients....

  1. 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.)

  2. 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 tumour cells and their association with the established biomarkers in BC. PATIENTS AND METHODS: In 324 BC from patients with long-term follow-up, the TGF-beta1 and TGF-betaRII transcript and protein expression levels were assessed. RESULTS: TGF-beta1 and TGF-betaRII down-expression was significantly...... associated with BC. Negative TGF-beta1 and TGF-betaRII protein status was associated with the development of distant metastasis (P = 0.003 and P = 0.029, respectively). In multivariate analysis, TGF-beta1-positive tumours were associated with increased disease-free survival (DFS) [hazard ratio (HR) = 0...

  3. Macrophage-tumour cell interactions: identification of MUC1 on breast cancer cells as a potential counter-receptor for the macrophage-restricted receptor, sialoadhesin.

    Science.gov (United States)

    Nath, D; Hartnell, A; Happerfield, L; Miles, D W; Burchell, J; Taylor-Papadimitriou, J; Crocker, P R

    1999-10-01

    In many carcinomas, infiltrating macrophages are commonly found closely associated with tumour cells but little is known concerning the nature or significance of adhesion molecules involved in these cellular interactions. Here we demonstrate in primary human breast cancers that sialoadhesin (Sn), a macrophage-restricted adhesion molecule, is frequently expressed on infiltrating cells that often make close contact with breast carcinoma cells. To determine whether Sn could act as a specific receptor for ligands on breast cancer cell lines, binding assays were performed with a recombinant form of the protein fused to the Fc portion of human immunoglobulin G1 (IgG1) (Sn-Fc). Sn-Fc was found to bind specifically and in a sialic acid-dependent manner to the breast cancer cell lines MCF-7, T47.D and BT-20 both in solid- and solution-phase binding assays. To investigate the nature of the sialoglycoproteins recognized by Sn on breast cancer cells, MCF-7 cells were labelled with [6-3H]glucosamine. Following precipitation with Sn-Fc, a major band of approximately 240000 MW was revealed, which was shown in reprecipitation and Western blotting experiments to be the epithelial mucin, MUC1.

  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. Tumour screening by means of tomography methods; Tumorscreening mit Schnittbildverfahren

    Energy Technology Data Exchange (ETDEWEB)

    Diederich, S. [Inst. fuer Diagnostische und Interventionelle Radiologie und Nuklearmedizin, Marien-Hospital Duesseldorf (Germany)

    2005-07-01

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

  6. Breast Cancer Diagnosed During Pregnancy: Adapting Recent Advances in Breast Cancer Care for Pregnant Patients.

    Science.gov (United States)

    Loibl, Sibylle; Schmidt, André; Gentilini, Oreste; Kaufman, Bella; Kuhl, Christine; Denkert, Carsten; von Minckwitz, Gunter; Parokonnaya, Anastasia; Stensheim, Hanne; Thomssen, Christoph; van Calsteren, Kristel; Poortmans, Philip; Berveiller, Paul; Markert, Udo R; Amant, Frederic

    2015-11-01

    Breast cancer during pregnancy (BCP), although rare, is becoming more common and treatment should be as similar as possible to that for nonpregnant young patients with breast cancer. A group of specialists convened to review current guidelines and provide guidance on how recent advances in breast cancer diagnosis and treatment can be adapted for pregnant patients. The majority of patients with BCP will be considered for treatment during the pregnancy. Premature delivery should be avoided whenever possible. Most treatments, including sentinel lymph node biopsy, systemic therapy with taxanes, platinum agents, or dose-dense treatment can be safely given during pregnancy, after careful risk/benefit assessment for mother and child. Chemotherapy is contraindicated during the first trimester because of a higher risk of fetal malformations but is feasible in the second and third trimesters. Other treatments such as radiation therapy or anti-human epidermal growth receptor 2 treatment are in general not indicated during pregnancy but might be considered in some instances. Patient data should be collected in a systematic way whenever possible.

  7. Brain metastasis reirradiation in patients with advanced breast cancer

    Science.gov (United States)

    Huang, Zhou; Sun, Bing; Shen, Ge; Cha, Lei; Meng, Xiangying; Wang, Junliang; Zhou, Zhenshan; Wu, Shikai

    2017-01-01

    The outcome of recurrent brain metastasis is dismal. This study aims to assess the clinical outcomes and toxicity of reirradiation as a salvage treatment for progressive brain metastasis in patients with advanced breast cancer. Between July 2005 and September 2014, the medical records of 56 patients with brain metastasis from breast cancer were retrospectively reviewed. Of these patients, 39 received whole-brain radiotherapy (WBRT) followed by stereotactic radiosurgery (SRS) reirradiation (Group 1), and 17 received SRS followed by WBRT reirradiation (Group 2). Overall survival (OS) and brain progression-free survival rates/times were calculated using the Kaplan–Meier method. Prognostic factors were evaluated using the Cox proportional hazards model. Change in neurologic function was also assessed. The median OS was 10.8 months (range, 1.3–56.8 months). In Group 1, the median PFS time (PFS-1) was 6.5 months and the OS time was 11.4 months. Multivariate analysis revealed that longer OS was significantly associated with a high Karnofsky performance score (KPS) (P = 0.004), controlled extracranial metastasis (P = 0.001) and a good response to reirradiation (P = 0.034). In Group 2, the median PFS time (PFS-2) after reirradiation was 8.5 months and the OS time was 10.8 months. Multivariate analysis revealed that longer OS was significantly associated with a high KPS (P = 0.018). The majority of the patients had improved or stable neurological function. Reirradiation is an effective and a safe treatment for patients with brain metastases from breast cancer. It might delay the progression of intracranial disease and improve neurological function. A suitable patient selection for reirradiation was suggested. PMID:27707842

  8. Recent advances in the development of breast cancer vaccines

    Directory of Open Access Journals (Sweden)

    Milani A

    2014-10-01

    Full Text Available Andrea Milani,1 Dario Sangiolo,1 Massimo Aglietta,1,2 Giorgio Valabrega1,2 1Department of Oncology, University of Torino, Torino, Italy; 2FPO, Candiolo Cancer Institute, IRCCS, Torino, Italy Abstract: The manipulation of the immune system through the administration of a vaccine to direct an effective and long-lasting immune response against breast cancer (BC cells is an attractive strategy. Vaccines would have several theoretical advantages over standard therapies, including low toxicities, high specificity, and long-lasting efficacy due to the establishment of immunological memory. However, BC vaccines have failed to demonstrate meaningful results in clinical trials so far. This reflects the intrinsic difficulty in breaking the complex immune-escaping mechanisms developed by cancer cells. New vaccines should be able to elicit complex immunologic response involving multiple immune effectors such as cytotoxic and antibody-secreting B cells, innate immunity effectors, and memory cells. Moreover, especially in patients with large tumor burdens and metastatic disease, combining vaccines with other strategies, such as systemic BC therapies, passive immunotherapy, or immunomodulatory agents, could increase the effectiveness of each approach. Here, we review recent advances in BC vaccines, focusing on suitable targets and innovative strategies. We report results of most recent trials investigating active immunotherapy in BC and provide possible future perspectives in this field of research. Keywords: breast cancer, cancer vaccines, cancer immunology, HER2, MUC-1, hTERT

  9. 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.)

  10. The value of archival tissue blocks in understanding breast cancer biology.

    Science.gov (United States)

    Dowsett, Thomas; Verghese, Eldo; Pollock, Steven; Pollard, Jennifer; Heads, Judith; Hanby, Andrew; Speirs, Valerie

    2014-03-01

    Pathological reporting of breast cancer has evolved alongside scientific advances. Such advances have led to recognition of different molecular classes of breast cancer resulting in improved disease management. The aim of this study was to establish whether these advances could be applied to archival breast cancer cases dating from the 1940s to assess historical trends. Important observations included the marked differences in pathological reporting, size of tumour and in ERα expression throughout the decades.

  11. Balloon catheter hypoxic pelvic perfusion with mitomycin C and melphalan for locally advanced tumours in the pelvic region : A phase I-II trial

    NARCIS (Netherlands)

    van Ijken, MGA; van Etten, B; Guetens, G; de Bruijn, EA; ten Hagen, TLM; Wiggers, T; Eggermont, AMM

    2005-01-01

    Aims: To investigate the feasibility of hypoxic pelvic perfusion (HPP), using balloon catheter techniques as treatment modality for locally advanced pelvic malignancies. Methods: In a phase I-II study, 16 patients with various non-resectabte pelvic tumours were treated with two HIPP with MMC and mel

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

    Energy Technology Data Exchange (ETDEWEB)

    Guarneri, Valentina; Conte, Pier Franco [Department of Oncology and Hematology, University of Modena and Reggio Emilia, Modena (Italy)

    2004-06-01

    Breast cancer represents a major health problem, with more than 1,000,000 new cases and 370,000 deaths yearly worldwide. In the last decade, in spite of an increasing incidence, breast cancer mortality has been declining in the majority of developed countries. This is the combined result of better education, widespread screening programmes and more efficacious adjuvant treatments. Better knowledge of breast cancer biology now allows the cosmetic, physical and psychological consequences of radical mastectomy to be spared in the majority of breast cancer patients. Use of the sentinel node technique is rapidly expanding and this will further reduce the extent and the consequences of surgery. Several clinico-pathological factors are used to discriminate between patients at low (<10%), average (10-40%) and high risk of relapse. Nodal status, tumour size, tumour grade and age are accepted universally as important factors to define risk categories. Newer factors such as uPA/PAI-1, HERer2-neu, proliferative indices and gene expression profile are promising and will allow better discrimination between patients at different risk. Endocrine manipulation with tamoxifen, ovarian ablation or both is the preferred option in the case of endocrine-responsive tumours. Tamoxifen administered for 5 years is the standard treatment for postmenopausal patients; tamoxifen plus ovarian ablation is more effective than tamoxifen alone for premenopausal women. Recent data demonstrate that, for postmenopausal patients, the aromatase inhibitors are superior to tamoxifen, with a different safety profile. At present, anastrozole can be used in the adjuvant setting in cases of tamoxifen intolerance or toxicity. Chemotherapy is the treatment of choice for steroid receptor-negative tumours. Polychemotherapy is superior to single agents and anthracycline-containing regimens are superior to CMF. Six courses of FEC or FAC or the sequential administration of four doses of anthracycline followed by four

  13. 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.

  14. 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.)

  15. CD3+, CD4+ & CD8+ tumour infiltrating lymphocytes (TILs are predictors of favourable survival outcome in infiltrating ductal carcinoma of breast

    Directory of Open Access Journals (Sweden)

    Ankita Singh Rathore

    2014-01-01

    Full Text Available Background & objectives: Tumour infiltrating lymphocytes (TILs represent the host immune response against cancer cells associated with good or bad prognosis in different tumour types. This study was undertaken to evaluate the significance of CD3+, CD4+ and CD8+ TILs in breast cancer tissues in relation to clinico-pathological variables and survival outcome. Methods: Immunohistochemistry (IHC was performed with antibodies against CD3, CD4 and CD8 antigens on formalin-fixed paraffin-embedded tissue sections of 150 breast cancer patients. Intratumoural and stromal TIL counting was performed semiquantitatively. Results: The higher CD3+, CD4+ and CD8+ intratumoural and stromal counts showed independent and direct association with good prognosis. The prognostic predictor value of intratumoural counts was higher than stromal counts. The independent associations of intratumoural and stromal counts became more prominent when adjusted with stage and grade, respectively. Among intratumoural counts, the high (++/+++ CD4+ count (OR=3.85, 95% CI=3.28-16.71, P<0.001 showed the highest survival followed by CD3+ (OR=2.70, 95% CI=1.76-8.30, P=0.001 and CD8+ (OR=2.58, 95% CI=1.55-5.86, p0 =0.001 the least when compared to respective low (+ counts. In contrast, among stromal counts, the high CD8+ count (OR=3.13, 95% CI=2.20-9.57, p0 <0.001 showed the highest survival followed by CD4+ (OR=3.02, 95% CI=2.07-8.89, p0 <0.001 and CD3+ (OR=2.45, 95% CI=1.53-6.73, p0 =0.002 the least. Interpretation & conclusions: Our results suggest that intratumoural CD4+ and stromal CD8+ counts by immunohistochemistry may serve as an independent prognosticator for favourable outcome in breast cancer.

  16. 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 ther...... immunoreactivity in tumour tissue from patients with primary epithelial ovarian cancer did not correlate with patient survival or response to combination platinum/cyclophosphamide therapy.......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...... 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...

  17. Effect of Obesity and Chronic Inflammation on TRAIL-Based Immunotherapy for Advanced Breast Cancer

    Science.gov (United States)

    2015-04-01

    Award Number: W81XWH-11-1-0271 TITLE: “Effect of obesity and chronic inflammation on TRAIL-based immunotherapy for advanced breast cancer...JAN 2015 4. TITLE AND SUBTITLE Effect of Obesity and Chronic Inflammation on TRAIL-Based Immunotherapy for Advanced Breast Cancer 5a. CONTRACT NUMBER...arise in cancer patients, rendering antitumor immune responses ineffective. In addition, epidemiological studies have demonstrated that obese

  18. [Rol of pituitary tumour-transforming gene (PTTG) in the pituitary adenomas].

    Science.gov (United States)

    Sánchez-Ortiga, Ruth; Sánchez Tejada, Laura; Peiró Cabrera, Gloria; Moreno-Pérez, Oscar; Arias Mendoza, Nieves; Aranda López, F Ignacio; Picó Alfonso, Antonio

    2010-01-01

    The pathogenesis of pituitary tumours is far to be understood. Pituitary transforming tumour gene (PTTG), a gen that induces aneuploidy, genetic instability, cellular proliferation and to stimulate angiogenesis, has been involved in neoplasic transformation and shown overexpressed in many neoplasm as lung, breast, endometrium, thyroid and colon malignant tumours. On the other hand, PTTG has been inconsistently studied in pituitary tumours. The majority of studies have been performed in animals and there is a great variability in the methods used in its determination. The goal of this review is to resume the role of PTTG in tumourogenesis and critically to revise the studies published in humans in order to advance in the knowledge of the pathogenesis of pituitary adenomas and to find clinical useful predictors of the behavior of these tumours.

  19. 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.

  20. 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.)

  1. 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

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

    Science.gov (United States)

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

    2011-06-01

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

  3. Incidental detection of breast cancer by {sup 68}Ga-DOTATOC-PET/CT in women suffering from neuroendocrine tumours

    Energy Technology Data Exchange (ETDEWEB)

    Elgeti, F.; Denecke, T.; Steffen, I.; Stelter, L.; Ruf, J. [Campus Virchow-Klinikum, Berlin (Germany). Klinik fuer Strahlenheilkunde; Amthauer, H. [Universitaetsklinikum Magdeburg (Germany). Klinik fuer Radilogie und Nuklearmedizin; Heuck, F. [Campus Virchow-Klinikum, Berlin (Germany). Medizinische Klinik m. S. Hepatologie und Gastroenterologie

    2008-07-01

    Aim: Somatostatin receptor (sstr) imaging using 68Ga- DOTATOC-PET/CT in neuroendocrine tumors (NET) is promising, suggesting a more sensitive detection of lesions with a low sstr-expression. This is also important for other sstr positive tumors, especially breast cancer whose incidence and age-range is similar to that of NET. Patients, methods: The PET/CT data of 33 consecutive women with NET (age: 33-78 years, mean 59) who underwent whole-body staging with {sup 6}8Ga-DOTATOC was retrospectively analyzed for breast lesions. The data was read separately, side-byside and as fused images. Focal tracer uptake in the breast was semiquantitatively analyzed by comparing the lesional SUV{sub max} to normal breast tissue using Wilcoxon's rank sum test. Breast cancer lesions were compared visually to concomitant NET- lesions. Results: In six of 33 patients (18%) breast lesions were observed on the CT-scans and classified in four patients (12%) as suspicious. The same lesions also showed a pathological tracer uptake on the corresponding PET-scan, visually and semiquantitatively (p<0.01). Histological reevaluation of the suspicious lesions revealed two patients with NET metastases. Two patients had primary breast cancer with lower tracer uptake than concomitant abdominal NET-lesions. Breast cancer diagnosis resulted in a change of the therapeutic regimen. Conclusion: {sup 68}Ga- DOTATOC-PET/CT not only improves the staging of NET-patients, but also increases the chance to detect sstr-positive breast cancer. Although these lesions may show a lower tracer uptake than NET, they must not be overlooked or misinterpreted as metastases. Further imaging and clarification by histopathology is warranted, as the confirmation of a secondary malignoma has great impact on further therapeutic proceedings. (orig.)

  4. Comprehensive genomic sequencing and the molecular profiles of clinically advanced breast cancer.

    Science.gov (United States)

    Ross, Jeffrey S; Gay, Laurie M

    2017-02-01

    Targeting specific mutations that have arisen within a tumour is a promising means of increasing the efficacy of treatments, and breast cancer is no exception to this new paradigm of personalised medicine. Traditional DNA sequencing methods used to characterise clinical cancer specimens and impact treatment decisions are highly sensitive, but are often limited in their scope to known mutational hot spots. Next-generation sequencing (NGS) technologies can also test for these well-known hot spots, as well as identifying insertions and deletions, copy number changes such as ERBB2 (HER2) gene amplification, and a wide array of fusion or rearrangement events. By rapidly analysing many genes in parallel, NGS technologies can make efficient use of precious biopsy material. Comprehensive genomic profiling (CGP) by NGS can reveal targetable, clinically relevant genomic alterations that can stratify tumours by predicted sensitivity to a variety of therapies, including HER2- or MTOR-targeted therapies, immunotherapies, and other kinase inhibitors. Many clinically relevant genomic alterations would not be identified by IHC or hotspot testing, but can be detected by NGS. In addition to the most common breast carcinoma subtypes, rare subtypes analysed with CGP also harbour clinically relevant genomic alterations that can potentially direct therapy selection, illustrating that CGP is a powerful tool for guiding treatment across all breast cancer subtypes.

  5. 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

  6. A randomized controlled trial comparing primary tumour resection plus systemic therapy with systemic therapy alone in metastatic breast cancer (PRIM-BC): Japan Clinical Oncology Group Study JCOG1017.

    Science.gov (United States)

    Shien, Tadahiko; Nakamura, Kenichi; Shibata, Taro; Kinoshita, Takayuki; Aogi, Kenjiro; Fujisawa, Tomomi; Masuda, Norikazu; Inoue, Kenichi; Fukuda, Haruhiko; Iwata, Hiroji

    2012-10-01

    This trial is being conducted to confirm the superiority, in terms of overall survival, of primary tumour resection plus systemic therapy to systemic therapy alone in patients with Stage IV breast cancer who are not refractory to primary systemic therapy. The inclusion criteria for the study are as follows: untreated patients with histologically confirmed invasive breast cancer with one or more measurable metastatic lesions diagnosed by radiological examination. All patients receive primary systemic therapy according to the estrogen receptor and human epidermal growth factor receptor type-2 status of the primary breast cancer after the first registration. After 3 months, the patients without disease progression are randomized to the primary tumour resection plus systemic therapy arm or the systemic therapy alone arm. The primary endpoint is the overall survival, and the secondary endpoints are proportion of patients without tumour progression at the metastatic sites, yearly local recurrence-free survival, proportion of local ulcer/local bleeding, yearly primary tumour resection-free survival, adverse events of chemotherapy, operative morbidity and serious adverse events. The patient recruitment was commenced in May 2011. Enrolment of 410 patients for randomization is planned over a 5 year recruitment period. We hereby report the details of the study.

  7. Common breast cancer susceptibility alleles are associated with tumour subtypes in BRCA1 and BRCA2 mutation carriers

    DEFF Research Database (Denmark)

    Mulligan, Anna Marie; Couch, Fergus J; Barrowdale, Daniel

    2011-01-01

    -negative breast cancer risk for both BRCA1 and BRCA2 carriers. In BRCA2 carriers, SNPs in FGFR2, TOX3, LSP1, SLC4A7/NEK10, 5p12, 2q35, and1p11.2 were significantly associated with ER-positive but not ER-negative disease. Similar results were observed when differentiating breast cancer cases by PR status...

  8. 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.

  9. Loco-regionally advance breast cancer: evaluation of management of breast cancer with special reference to multimodal approach

    Directory of Open Access Journals (Sweden)

    Anshuman Panda

    2016-11-01

    Conclusions: Patients with LBAC who are able to complete treatment with chemotherapy, mastectomy, and postmastectomy radiation have a high probability of locoregional control. Neo-adjuvant chemotherapy can make inoperable locally advanced breast cancer operable and with the use of neo-adjuvant CT, breast conservation surgery is possible even in locally advanced breast cancer. Use of post-operative CT and RT can increase the disease free survival period. Use of multimodal treatment in the form of CT, surgery and radiotherapy can increase the disease free survival period in locally advanced breast cancer. The advent of successful multimodal regimens incorporating systemic treatment (chemotherapy or chemohormonal therapy as well as local therapy (surgery and radiation has significantly improved disease-free and overall survival as well as local-regional control. Longer follow-up of these conservatively treated patients will be needed, however, to determine whether local-regional control is preserved. [Int J Res Med Sci 2016; 4(11.000: 4767-4777

  10. Reducing the Human Burden of Breast Cancer: Advanced Radiation Therapy Yields Improved Treatment Outcomes.

    Science.gov (United States)

    Currey, Adam D; Bergom, Carmen; Kelly, Tracy R; Wilson, J Frank

    2015-01-01

    Radiation therapy is an important modality in the treatment of patients with breast cancer. While its efficacy in the treatment of breast cancer was known shortly after the discovery of x-rays, significant advances in radiation delivery over the past 20 years have resulted in improved patient outcomes. With the development of improved systemic therapy, optimizing local control has become increasingly important and has been shown to improve survival. Better understanding of the magnitude of treatment benefit, as well as patient and biological factors that confer an increased recurrence risk, have allowed radiation oncologists to better tailor treatment decisions to individual patients. Furthermore, significant technological advances have occurred that have reduced the acute and long-term toxicity of radiation treatment. These advances continue to reduce the human burden of breast cancer. It is important for radiation oncologists and nonradiation oncologists to understand these advances, so that patients are appropriately educated about the risks and benefits of this important treatment modality.

  11. 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

  12. Inhibition of Wnt signalling and breast tumour growth by the multi-purpose drug suramin through suppression of heterotrimeric G proteins and Wnt endocytosis.

    Science.gov (United States)

    Koval, Alexey; Ahmed, Kamal; Katanaev, Vladimir L

    2016-02-15

    Overactivation of the Wnt signalling pathway underlies oncogenic transformation and proliferation in many cancers, including the triple-negative breast cancer (TNBC), the deadliest form of tumour in the breast, taking about a quarter of a million lives annually worldwide. No clinically approved targeted therapies attacking Wnt signalling currently exist. Repositioning of approved drugs is a promising approach in drug discovery. In the present study we show that a multi-purpose drug suramin inhibits Wnt signalling and proliferation of TNBC cells in vitro and in mouse models, inhibiting a component in the upper levels of the pathway. Through a set of investigations we identify heterotrimeric G proteins and regulation of Wnt endocytosis as the likely target of suramin in this pathway. G protein-dependent endocytosis of plasma membrane-located components of the Wnt pathway was previously shown to be important for amplification of the signal in this cascade. Our data identify endocytic regulation within Wnt signalling as a promising target for anti-Wnt and anti-cancer drug discovery. Suramin, as the first example of such drug or its analogues might pave the way for the appearance of first-in-class targeted therapies against TNBC and other Wnt-dependent cancers.

  13. Co-expression of tenascin-C and vimentin in human breast cancer cells indicates phenotypic transdifferentiation during tumour progression: correlation with histopathological parameters, hormone receptors, and oncoproteins.

    Science.gov (United States)

    Dandachi, N; Hauser-Kronberger, C; Moré, E; Wiesener, B; Hacker, G W; Dietze, O; Wirl, G

    2001-02-01

    Loss of epithelial morphology and the acquisition of mesenchymal characteristics are typical for carcinoma cells in tumour progression. In human breast carcinomas, up-regulation of tenascin-C (TN-C) and vimentin (Vim) is frequently observed in cancer cells and correlates with increased malignancy. Thus, it is possible that TN-C is co-expressed with Vim, representing cancer cells that have undergone epithelial-mesenchymal transition (EMT). This study examined 128 breast carcinomas using immunohistochemical techniques to demonstrate that mammary cancer cells are a prominent source of both TN-C and Vim. Statistical analysis revealed a significant association between TN-C and Vim expression in cancer cells. TN-C expression also correlated positively with overexpression of c-erbB-2 oncoprotein and down-regulation of oestrogen receptors (ERs). Eleven human mammary cancer cell lines and two 'normal' cell lines were examined by western blotting and immunohistochemistry. Co-expression of TN-C and Vim was detected in the carcinosarcoma cell line HS 578T, SK-BR-3 (B), fibroblast-like MDA-MB-231 cells, and the myoepithelial cell line HBL 100. These findings suggest that TN-C and Vim, when co-expressed in mammary carcinoma cells, represent regulator genes likely to be involved in EMT during mammary carcinogenesis.

  14. 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; Ege Olsen, Karen;

    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...... receptor (p prognosis. In multivariate analysis, metastatic nodes (1-3 positive: RR 1.56 95% CI 1.02-2.38; >3 positive: RR 3.70 95% CI 2.54-5.38), HER2+ (RR 1.91, 95% CI 1.35-2.70), mutated TP53 (RR 1.70, 95% CI 1.21-2.38), PAI-1 (RR 1.04, 95% CI 1.......01-1.07) and grade 3 (RR 1.96, 95% CI 1.83-3.22) were independent markers of poor outcome. CONCLUSION: Compared to PAI-1 protein levels, Chalkley counts and MIB-1, HER2+ and mutations of TP53 were the strongest independent markers of poor prognosis irrespective of nodal status....

  15. 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.

  16. Preoperative axillary lymph node evaluation in breast cancer patients by breast magnetic resonance imaging (MRI): Can breast MRI exclude advanced nodal disease?

    Energy Technology Data Exchange (ETDEWEB)

    Hyun, Su Jeong [Yonsei University College of Medicine, Department of Radiology, Breast Cancer Clinic, Severance Hospital, Research Institute of Radiological Science, Seoul (Korea, Republic of); Hallym University Medical Center, Department of Radiology, Kangnam Sacred Heart Hospital, Seoul (Korea, Republic of); Kim, Eun-Kyung; Moon, Hee Jung; Yoon, Jung Hyun; Kim, Min Jung [Yonsei University College of Medicine, Department of Radiology, Breast Cancer Clinic, Severance Hospital, Research Institute of Radiological Science, Seoul (Korea, Republic of)

    2016-11-15

    To evaluate the diagnostic performance of breast magnetic resonance imaging (MRI) in preoperative evaluation of axillary lymph node metastasis (ALNM) in breast cancer patients and to assess whether breast MRI can be used to exclude advanced nodal disease. A total of 425 patients were included in this study and breast MRI findings were retrospectively reviewed. The diagnostic performance of breast MRI for diagnosis of ALNM was evaluated in all patients, patients with neoadjuvant chemotherapy (NAC), and those without NAC (no-NAC). We evaluated whether negative MRI findings (cN0) can exclude advanced nodal disease (pN2-pN3) using the negative predictive value (NPV) in each group. The sensitivity and NPV of breast MRI in evaluation of ALNM was 51.3 % (60/117) and 83.3 % (284/341), respectively. For cN0 cases on MRI, pN2-pN3 manifested in 1.8 % (6/341) of the overall patients, 0.4 % (1/257) of the no-NAC group, and 6 % (5/84) of the NAC group. The NPV of negative MRI findings for exclusion of pN2-pN3 was higher for the no-NAC group than for the NAC group (99.6 % vs. 94.0 %, p = 0.039). Negative MRI findings (cN0) can exclude the presence of advanced nodal disease with an NPV of 99.6 % in the no-NAC group. (orig.)

  17. [Commentary to the paper: immobilising malignant phyllodes tumour of the breast by E. Fritsche, U. Hug und D. Winterholer].

    Science.gov (United States)

    Horch, R E

    2015-04-01

    The size of a tumor should not be the limiting factor when it comes to the decision for surgical treatment of such entities. Due to modern plastic reconstructive techniques an R0 situaiton should always be attempted, and in the worst case an interdisciplinary palliative resection should be possible and recommendable. As the present case with a tumour that led to immobility clearly indicates, the gain in quality of life undoubtedly is a proof of the necessity and value of the surgical treatment of this entity.

  18. Impact of biliary stent-related events in patients diagnosed with advanced pancreatobiliary tumours receiving palliative chemotherapy

    Science.gov (United States)

    Lamarca, Angela; Rigby, Christina; McNamara, Mairéad G; Hubner, Richard A; Valle, Juan W

    2016-01-01

    AIM: To determine the impact (morbidity/mortality) of biliary stent-related events (SRE) (cholangitis or stent obstruction) in chemotherapy-treated pancreatico-biliary patients. METHODS: All consecutive patients with advanced pancreatobiliary cancer and a biliary stent in-situ prior to starting palliative chemotherapy were identified retrospectively from local electronic case-note records (Jan 13 to Jan 15). The primary end-point was SRE rate and the time-to-SRE (defined as time from first stenting before chemotherapy to date of SRE). Progression-free survival and overall survival were measured from the time of starting chemotherapy. Kaplan-Meier, Cox and Fine-Gray regression (univariate and multivariable) analyses were employed, as appropriate. For the analysis of time-to-SRE, death was considered as a competing event. RESULTS: Ninety-six out of 693 screened patients were eligible; 89% had a metal stent (the remainder were plastic). The median time of follow-up was 9.6 mo (range 2.2 to 26.4). Forty-one patients (43%) developed a SRE during follow-up [cholangitis (39%), stent obstruction (29%), both (32%)]. There were no significant differences in baseline characteristics between the SRE group and no-SRE groups. Recorded SRE-consequences were: none (37%), chemotherapy delay (24%), discontinuation (17%) and death (22%). The median time-to-SRE was 4.4 mo (95%CI: 3.6-5.5). Patients with severe comorbidities (P < 0.001) and patients with ≥ 2 baseline stents/biliary procedures [HR = 2.3 (95%CI: 1.2-4.44), P = 0.010] had a shorter time-to-SRE on multivariable analysis. Stage was an independent prognostic factor for overall survival (P = 0.029) in the multivariable analysis adjusted for primary tumour site, performance status and development of SRE (SRE group vs no-SRE group). CONCLUSION: SREs are common and impact on patient’s morbidity. Our results highlight the need for prospective studies exploring the role of prophylactic strategies to prevent/delay SREs. PMID

  19. 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.

  20. The prognostic and predictive power of redox protein expression for anthracycline-based chemotherapy response in locally advanced breast cancer

    Science.gov (United States)

    Woolston, Caroline M; Zhang, Lei; Storr, Sarah J; Al-Attar, Ahmad; Shehata, Mohamed; Ellis, Ian O; Chan, Stephen Y; Martin, Stewart G

    2012-01-01

    Neoadjuvant chemotherapy has become the standard of care for locally advanced primary breast cancer. Anthracycline-based regimens have proven to be one of the most effective treatments in this setting. As certain cytotoxic antineoplastic agents, such as anthracyclines, generate reactive oxygen species as a by-product of their mechanism of action, we examined whether redox protein expression was involved in the response to anthracycline-based chemotherapy and with clinical outcome. Pre-treatment needle core biopsy and post-anthracycline treatment tumour sections were analysed from 98 cases. In all, 32 individuals had a complete clinical response and 17 had a complete pathological response. Immunohistochemical staining was performed for eight redox proteins: thioredoxin, thioredoxin reductase, thioredoxin interacting protein (TxNIP), glutathione S-transferase (GST) π, θ and α, catalase and manganese superoxide dismutase. GST π (P=0.05) and catalase (P=0.045) were associated with pathological complete response in pre-chemotherapy samples. TxNIP (P=0.017) and thioredoxin reductase (P=0.022) were independent prognostic factors for distant metastasis-free survival and TxNIP for overall survival (P=0.014). In oestrogen receptor negative patients that are known to have a poor overall survival, a considerably worse prognosis was seen in cases that exhibited low expression of TxNIP (P=0.000003), stratifying patients into more defined groups. This study indicates the importance of redox regulation in determining breast cancer response to anthracycline-based chemotherapy and provides ways of further stratifying pre-chemotherapy patients to potentially allow more tailored treatments. PMID:22481283

  1. Oncologic safety of breast conserving surgery after tumour downsizing by neoadjuvant therapy: a retrospective single centre cohort study.

    Science.gov (United States)

    Fitzal, F; Riedl, O; Mittlböck, M; Dubsky, P; Bartsch, R; Steger, G; Jakesz, R; Gnant, M

    2011-05-01

    The objective of this study is to analyse local recurrence rates in patients receiving neoadjuvant chemotherapy (nCT) comparing mastecomized (MX) patients with those undergoing breast conserving therapy (BCT). Patients undergoing breast cancer surgery after nCT (3xCMF or 3-6xED) between 1995 and 2007 at our department were retrospectively analysed. The median follow up was 60 months for 308 patients. Patients who were downsized from MX to BCT with partial or complete response (n = 104) had a similar local recurrence free survival (LRFS) compared to patients who did not experience successful downsizing (n = 67) and finally undergoing MX (LRFS MX-BCT 81% vs. MX-MX 91%; P = 0.79). Uni- and multivariate analyses demonstrated that BCT itself was not an independent prognostic factor for a worse LRFS (P = 0.07 and 0.14). After no pathologic change or progressive disease the risk of local recurrence was increased in patients undergoing BCT (MX-BCT; n = 6 LRFS 66%) compared with MX (n = 44; LRFS 90%; P = 0.04). Overall survival in general was better for the BCT group (n = 197) compared with MX group (n = 111) regardless of clinical response (92% vs. 72%; P downsizing by nCT in patients primarily scheduled for mastectomy. These patients, however, should not be treated with breast conservation in the absence of any proven response after nCT.

  2. Imaging in the evaluation and follow-up of early and advanced breast cancer: When, why, and how often?

    Science.gov (United States)

    Bychkovsky, Brittany L; Lin, Nancy U

    2017-02-01

    Imaging in the evaluation and follow-up of patients with early or advanced breast cancer is an important aspect of cancer care. The role of imaging in breast cancer depends on the goal and should only be performed to guide clinical decisions. Imaging is valuable if a finding will change the course of treatment and improve outcomes, whether this is disease-free survival, overall survival or quality-of-life. In the last decade, imaging is often overused in oncology and contributes to rising healthcare costs. In this context, we review the data that supports the appropriate use of imaging for breast cancer patients. We will discuss: 1) the optimal use of staging imaging in both early (Stage 0-II) and locally advanced (Stage III) breast cancer, 2) the role of surveillance imaging to detect recurrent disease in Stage 0-III breast cancer and 3) how patients with metastatic breast cancer should be followed with advanced imaging.

  3. Selective androgen receptor modulators as improved androgen therapy for advanced breast cancer.

    Science.gov (United States)

    Coss, Christopher C; Jones, Amanda; Dalton, James T

    2014-11-01

    Androgens were at one time a therapeutic mainstay in the treatment of advanced breast cancer. Despite comparable efficacy, SERMs and aromatase inhibitors eventually became the therapies of choice due to in part to preferred side-effect profiles. Molecular characterization of breast tumors has revealed an abundance of androgen receptor expression but the choice of an appropriate androgen receptor ligand (agonist or antagonist) has been confounded by multiple conflicting reports concerning the role of the receptor in the disease. Modern clinical efforts have almost exclusively utilized antagonists. However, the recent clinical development of selective androgen receptor modulators with greatly improved side-effect profiles has renewed interest in androgen agonist therapy for advanced breast cancer.

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

    OpenAIRE

    Zinser-Sierra Juan; Bargallo-Rocha Enrique; Morales-Barrera Rafael; Saavedra-Perez David; Gamboa-Vignolle Carlos; Arrieta Oscar; Alvarado-Miranda Alberto; Perez-Sanchez Victor; Ramirez-Ugalde Teresa; Lara-Medina Fernando

    2009-01-01

    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 cyclophosphamid...

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

    OpenAIRE

    Tomas Kron; Boon Chua

    2014-01-01

    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 dist...

  6. Endocrine treatment options for advanced breast cancer--the role of fulvestrant.

    NARCIS (Netherlands)

    Robertson, J.F.; Come, S.E.; Jones, S.; Beex, L.V.A.M.; Kaufmann, Martin; Makris, A.; Nortier, J.W.; Possinger, K.; Rutqvist, L.E.

    2005-01-01

    For many years, tamoxifen has been the 'gold standard' amongst anti-oestrogen therapies for breast cancer. However, the selective aromatase inhibitors (AIs), anastrozole, letrozole and exemestane, have demonstrated advantages over tamoxifen as first-line treatments for advanced disease. Anastrozole

  7. Caring for Patients with Advanced Breast Cancer: The Experiences of Zambian Nurses

    Science.gov (United States)

    Maree, Johanna Elizabeth; Mulonda, Jennipher Kombe

    2017-01-01

    Objective: The objective of this study was to describe the experiences of Zambian nurses caring for women with advanced breast cancer. Methods: We used a qualitative descriptive design and purposive sampling. Seventeen in-depth interviews were conducted with registered nurses practicing in the Cancer Diseases Hospital and the University Teaching Hospital, Lusaka, Zambia, and analyzed using thematic analyses. Results: Two themes emerged from the data - caring for women with advanced breast cancer is challenging and the good outweighs the bad. The majority of the participants agreed that caring for women with advanced breast cancer and witnessing their suffering were challenging. Not having formal education and training in oncology nursing was disempowering, and one of the various frustrations participants experienced. The work environment, learning opportunities, positive patient outcomes, and the opportunity to establish good nurse–patient experiences were positive experiences. Conclusions: Although negative experiences seemed to be overwhelming, participants reported some meaningful experiences while caring for women with advanced breast cancer. The lack of formal oncology nursing education and training was a major factor contributing to their negative experiences and perceived as the key to rendering the quality of care patients deserved. Ways to fulfill the educational needs of nurses should be explored and instituted, and nurses should be remunerated according to their levels of practice. PMID:28217726

  8. Weekly low-dose mitoxantrone plus doxorubicin as second-line chemotherapy for advanced breast cancer

    NARCIS (Netherlands)

    M. Bontenbal (Marijke); A.S.Th. Planting (André); C.J. Rodenburg (C.); A. Dees; J. Verweij (Jaap); C.C.M. Bartels (Carina); J. Alexieva-Figusch (Jana); W.L.J. van Putten (Wim); J.G.M. Klijn (Jan)

    1992-01-01

    textabstractWeekly low dose mitoxantrone (3 mg/m2) plus doxorubicin (8 mg/m2) was administered as second-line chemotherapy to 33 patients with advanced breast cancer. Four out of 28 evaluable patients (14%) obtained a partial response with a median duration of 34 weeks (range 18-67+ weeks), while 8

  9. 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.

  10. Pitfalls in colour photography of choroidal tumours.

    Science.gov (United States)

    Schalenbourg, A; Zografos, L

    2013-02-01

    Colour imaging of fundus tumours has been transformed by the development of digital and confocal scanning laser photography. These advances provide numerous benefits, such as panoramic images, increased contrast, non-contact wide-angle imaging, non-mydriatic photography, and simultaneous angiography. False tumour colour representation can, however, cause serious diagnostic errors. Large choroidal tumours can be totally invisible on angiography. Pseudogrowth can occur because of artefacts caused by different methods of fundus illumination, movement of reference blood vessels, and flattening of Bruch's membrane and sclera when tumour regression occurs. Awareness of these pitfalls should prevent the clinician from misdiagnosing tumours and wrongfully concluding that a tumour has grown.

  11. Pitfalls in colour photography of choroidal tumours

    Science.gov (United States)

    Schalenbourg, A; Zografos, L

    2013-01-01

    Colour imaging of fundus tumours has been transformed by the development of digital and confocal scanning laser photography. These advances provide numerous benefits, such as panoramic images, increased contrast, non-contact wide-angle imaging, non-mydriatic photography, and simultaneous angiography. False tumour colour representation can, however, cause serious diagnostic errors. Large choroidal tumours can be totally invisible on angiography. Pseudogrowth can occur because of artefacts caused by different methods of fundus illumination, movement of reference blood vessels, and flattening of Bruch's membrane and sclera when tumour regression occurs. Awareness of these pitfalls should prevent the clinician from misdiagnosing tumours and wrongfully concluding that a tumour has grown. PMID:23238442

  12. 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

  13. Lapatinib for treatment of advanced or metastasized breast cancer: systematic review

    Directory of Open Access Journals (Sweden)

    Rachel Riera

    Full Text Available CONTEXT AND OBJECTIVE: Around 16% to 20% of women with breast cancer have advanced, metastasized breast cancer. At this stage, the disease is treatable, but not curable. The objective here was to assess the effectiveness of lapatinib for treating patients with advanced or metastasized breast cancer. DESIGN AND SETTING: Systematic review of the literature, developed at Centro Paulista de Economia da Saúde (CPES, Universidade Federal de São Paulo (Unifesp. METHOD: Systematic review with searches in virtual databases (PubMed, Lilacs [Literatura Latino-Americana e do Caribe em Ciências da Saúde], Cochrane Library, Scirus and Web of Science and manual search. RESULTS: Only one clinical trial that met the selection criteria was found. This study showed that lapatinib in association with capecitabine reduced the risk of cancer progression by 51% (95% confidence interval, CI: 0.34-0.71; P < 0.001, compared with capecitabine alone, without any increase in severe adverse effects. CONCLUSION: The combination of lapatinib plus capecitabine was more effective than capecitabine alone for reducing the risk of cancer progression. Further randomized clinical trials need to be carried out with the aim of assessing the effectiveness of lapatinib as monotherapy or in association for first-line or second-line treatment of advanced breast cancer.

  14. Tumour biological prognosis factors in advanced-stage uterus cervical carcinoma treated primarily by radiation therapy. A study on the significance of tumour oxygenation, tumour vascularisatio, anaemia and tumour proteins for the clinical treatment outcome; Tumorbiologische Prognosefaktoren beim fortgeschrittenen, primaer strahlentherapeutisch behandelten Uteruszervixkarzinom. Eine Untersuchung zur Bedeutung von Tumoroxygenierung, Tumorvaskularisation, Anaemie und Tumorproteinen fuer das klinische Behandlungsergebnis

    Energy Technology Data Exchange (ETDEWEB)

    Haensgen, G.

    2002-07-01

    The goal of the present study was to evaluate tumour biological prognosis factors that might give an indication of a patient's probable radiation sensitivity and hence of the probable clinical outcome. The ultimate goal was to reveal relationships between special tumour biological circumstances and clinical results that would permit a definition of risk factors, thus facilitating an individualised, i.e. optimised treatment.

  15. 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

  16. 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

  17. 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.

  18. 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

  19. Surgery for Breast Cancer

    Science.gov (United States)

    ... Cancer During Pregnancy Breast Cancer Breast Cancer Treatment Surgery for Breast Cancer Surgery is a common treatment ... removed (breast reconstruction) Relieve symptoms of advanced cancer Surgery to remove breast cancer There are two main ...

  20. 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.

  1. 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.

  2. 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.

  3. 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.)

  4. 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

  5. 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...... and TLG. The secondary end point was overall survival (OS) according to cfDNA, MTV and TLG.Results:Fifty-three patients were included. There were no correlations between cfDNA and MTV (r=0.1) or TLG (r=0.1). cfDNA >75th percentile was correlated with shorter OS (P=0.02), confirmed in a multivariate...... burden defined by positron emission tomography (PET) parameters.Methods:Patients with advanced non-small cell lung cancer (NSCLC) were enrolled into a prospective biomarker trial. Before treatment, plasma was extracted and the level of cfDNA was determined by qPCR. An (18)F-fluorodeoxyglucose ((18)F...

  6. TU-EF-207-04: Advances in Detector Technology for Breast Tomosynthesis

    Energy Technology Data Exchange (ETDEWEB)

    Zhao, W. [SUNY Stony Brook (United States)

    2015-06-15

    Breast imaging technology is advancing on several fronts. In digital mammography, the major technological trend has been on optimization of approaches for performing combined mammography and tomosynthesis using the same system. In parallel, photon-counting slot-scan mammography is now in clinical use and more efforts are directed towards further development of this approach for spectral imaging. Spectral imaging refers to simultaneous acquisition of two or more energy-windowed images. Depending on the detector and associated electronics, there are a number of ways this can be accomplished. Spectral mammography using photon-counting detectors can suppress electronic noise and importantly, it enables decomposition of the image into various material compositions of interest facilitating quantitative imaging. Spectral imaging can be particularly important in intravenously injected contrast mammography and eventually tomosynthesis. The various approaches and applications of spectral mammography are discussed. Digital breast tomosynthesis relies on the mechanical movement of the x-ray tube to acquire a number of projections in a predefined arc, typically from 9 to 25 projections over a scan angle of +/−7.5 to 25 degrees depending on the particular system. The mechanical x-ray tube motion requires relatively long acquisition time, typically between 3.7 to 25 seconds depending on the system. Moreover, mechanical scanning may have an effect on the spatial resolution due to internal x-ray filament or external mechanical vibrations. New x-ray source arrays have been developed and they are aimed at replacing the scanned x-ray tube for improved acquisition time and potentially for higher spatial resolution. The potential advantages and challenges of this approach are described. Combination of digital mammography and tomosynthesis in a single system places increased demands on certain functional aspects of the detector and overall performance, particularly in the tomosynthesis

  7. TU-EF-207-01: Introductory Remarks on Recent Advances in Breast Imaging

    Energy Technology Data Exchange (ETDEWEB)

    Karellas, A. [University of Massachusetts Medical School (United States)

    2015-06-15

    Breast imaging technology is advancing on several fronts. In digital mammography, the major technological trend has been on optimization of approaches for performing combined mammography and tomosynthesis using the same system. In parallel, photon-counting slot-scan mammography is now in clinical use and more efforts are directed towards further development of this approach for spectral imaging. Spectral imaging refers to simultaneous acquisition of two or more energy-windowed images. Depending on the detector and associated electronics, there are a number of ways this can be accomplished. Spectral mammography using photon-counting detectors can suppress electronic noise and importantly, it enables decomposition of the image into various material compositions of interest facilitating quantitative imaging. Spectral imaging can be particularly important in intravenously injected contrast mammography and eventually tomosynthesis. The various approaches and applications of spectral mammography are discussed. Digital breast tomosynthesis relies on the mechanical movement of the x-ray tube to acquire a number of projections in a predefined arc, typically from 9 to 25 projections over a scan angle of +/−7.5 to 25 degrees depending on the particular system. The mechanical x-ray tube motion requires relatively long acquisition time, typically between 3.7 to 25 seconds depending on the system. Moreover, mechanical scanning may have an effect on the spatial resolution due to internal x-ray filament or external mechanical vibrations. New x-ray source arrays have been developed and they are aimed at replacing the scanned x-ray tube for improved acquisition time and potentially for higher spatial resolution. The potential advantages and challenges of this approach are described. Combination of digital mammography and tomosynthesis in a single system places increased demands on certain functional aspects of the detector and overall performance, particularly in the tomosynthesis

  8. 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.

  9. Endocrinological and clinical evaluation of two doses of formestane in advanced breast cancer.

    OpenAIRE

    Bajetta, E; Zilembo, N.; Buzzoni, R.; Noberasco, C.; Di Leo, A; Bartoli, C.; Merson, M; Sacchini, V.; Moglia, D; Celio, L.

    1994-01-01

    Formestane is a selective inhibitor of oestrogen synthesis by aromatase enzymes and induces disease regression in breast cancer patients. This phase II randomised study was carried out to determine whether there were any differences in the effects of two different doses of formestane on oestradiol (E2) serum levels and to evaluate the corresponding clinical activity in post-menopausal patients with positive or unknown oestrogen receptor status pretreated or not for advanced disease. Furthermo...

  10. Breast-conserving surgery in locally advanced breast cancer submitted to neoadjuvant chemotherapy. Safety and effectiveness based on ipsilateral breast tumor recurrence and long-term follow-up

    Science.gov (United States)

    Carrara, Guilherme Freire Angotti; Scapulatempo-Neto, Cristovam; Abrahão-Machado, Lucas Faria; Brentani, Maria Mitzi; Nunes, João Soares; Folgueira, Maria Aparecida Azevedo Koike; da Costa Vieira, René Aloisio

    2017-01-01

    OBJECTIVE: To evaluate ipsilateral breast tumor recurrence after breast-conserving surgery for locally advanced breast cancer. METHODS: A retrospective observational cohort study was performed in patients with locally advanced breast cancer submitted to breast-conserving surgery after neoadjuvant chemotherapy based on an adriamycin-cyclophosphamide-paclitaxel regimen. We evaluated the clinical, pathologic, immunohistochemistry, and surgical factors that contribute to ipsilateral breast tumor recurrence and locoregional recurrence. A Kaplan-Meier analysis and Cox model were used to evaluate the main factors related to disease-free survival. RESULTS: Of the 449 patients who received neoadjuvant chemotherapy, 98 underwent breast-conserving surgery. The average diameter of the tumors was 5.3 cm, and 87.2% reached a size of up to 3 cm. Moreover, 86.7% were classified as clinical stage III, 74.5% had T3-T4 tumors, 80.5% had N1-N2 axilla, and 89.8% had invasive ductal carcinoma. A pathologic complete response was observed in 27.6% of the tumors, and 100.0% of samples had free margins. The 5-year actuarial overall survival rate was 81.2%, and the mean follow-up was 72.8 months. The rates of ipsilateral breast tumor recurrence and locoregional recurrence were 11.2% and 15.3%, respectively. Multifocal morphology response was the only factor related to ipsilateral breast tumor recurrence disease-free survival (p=0.04). A multivariate analysis showed that the pathologic response evaluation criteria in solid tumors (RECIST)-breast cutoff was the only factor related to locoregional recurrence disease-free survival (p=0.01). CONCLUSIONS: Breast-conserving surgery is a safe and effective therapy for selected locally advanced breast tumors. PMID:28355358

  11. Treatment of advanced breast cancer with chinese medicinal herbs of Fei decoction: a case report.

    Science.gov (United States)

    Lv, G M; Hu, M; Chen, R Z; Zhu, L L; Tao, Ch J; Xia, X D; Gong, Y L; Li, P; Wan, H J

    2014-01-01

    A 46-year-old female underwent surgery for cancer of the right breast mammary (T3N2M0) in Sep 2010. Following post surgery, adjuvant chemotherapy of CAF regimens (cyclophosphamide+adriamycin+fluorouracil) was administered. Two years later, multiple pulmonary and skeletal metastatic lesions had been found by CT (computerized tomography) and ECT (emission computed tomograph) imaging. She received the treatment of second-line chemotherapy regimens of GP (cisplatin + gemcitabine). In the meantime, we administered Chinese traditional herb drugs (Fei Decoction, mixed a variety of effective herbal components) to help her recover from the poor condition. After taking the Chinese herbs for 2 months, the tumour marker (CEA, CA15-3) dramatically decreased, resulting in the normal range. Both lung and bone metastatic sites reduced according to CT and ECT imaging, and the patient felt free from the complaint of pulmonary and cardiac discomfort. Over time, the quality of life has been greatly improved, we have managed to prolong the PFS (progression-free-survival) and TTP (time-to-progression) from the onset to date. CTM (Chinese traditional medicine) considers human body as a dynamic platform in which all organs are correlative and bind each other. Relationship between heart, liver, spleen, lung and kidney is like an interlink between mother and son, and runs in cycle as a circle. In the course of this combined treatment, we showed that Chinese herbal medicine played an important role in the therapy of breast cancer. Chinese herbs might be an additional choice with their better benefits and tolerability in the treatment of recurrent breast cancer.

  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. WDR26 in Advanced Breast Cancer: A Novel Regulator of the P13K/AKT Pathway

    Science.gov (United States)

    2015-10-01

    AWARD NUMBER: W81XWH-14-1-0539 TITLE: WDR26 in Advanced Breast Cancer : A Novel Regulator of the P13K/AKT Pathway PRINCIPAL INVESTIGATOR...5a. CONTRACT NUMBER WDR26 in Advanced Breast Cancer : A Novel Regulator of the P13K/AKT Pathway 5b. GRANT NUMBER W81XWH-14-1-0539 5c. PROGRAM...SUPPLEMENTARY NOTES 14. ABSTRACT The PI3K/AKT pathway is one of the most deregulated pathways in breast cancers (>70%), and a major contributor to tumor

  15. 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

  16. 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

    2006-10-09

    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.

  17. Doppler ultrasound scoring to predict chemotherapeutic response in advanced breast cancer

    Directory of Open Access Journals (Sweden)

    Singh Tej B

    2007-08-01

    Full Text Available Abstract Background Doppler ultrasonography (US is increasingly being utilized as an imaging modality in breast cancer. It is used to study the vascular characteristics of the tumor. Neoadjuvant chemotherapy is the standard modality of treatment in locally advanced breast cancer. Histological examination remains the gold standard to assess the chemotherapy response. However, based on the color Doppler findings, a new scoring system that could predict histological response following chemotherapy is proposed. Methods Fifty cases of locally advanced infiltrating duct carcinoma of the breast were studied. The mean age of the patients was 44.5 years. All patients underwent clinical, Doppler and histopathological assessment followed by three cycles of CAF (Cyclophosphamide, Adriamycin and 5-Fluorouracil chemotherapy, repeat clinical and Doppler examination and surgery. The resected specimens were examined histopathologically and histological response was correlated with Doppler findings. The Doppler characteristics of the tumor were graded as 1–4 for 50% and complete disappearance of flow signals respectively. A cumulative score was calculated and compared with histopathological response. Results were analyzed using Chi square test, sensitivity, specificity, positive and negative predictive values. Results The maximum Doppler score according to the proposed scoring system was twelve and minimum three. Higher scores corresponded with a more favorable histopathological response. Twenty four patients had complete response to chemotherapy. Sixteen of these 24 patients (66.7% had a cumulative Doppler score more than nine. The sensitivity of cumulative score >5 was 91.7% and specificity was 38.5%. The area under the ROC curve of the cumulative score >9 was 0.72. Conclusion Doppler scoring can be accurately used to objectively predict the response to chemotherapy in patients with locally advanced breast cancer and it correlates well with histopathological

  18. Doppler ultrasound scoring to predict chemotherapeutic response in advanced breast cancer

    Science.gov (United States)

    Kumar, Anand; Singh, Seema; Pradhan, Satyajit; Shukla, Ram C; Ansari, Mumtaz A; Singh, Tej B; Shyam, Rohit; Gupta, Saroj

    2007-01-01

    Background Doppler ultrasonography (US) is increasingly being utilized as an imaging modality in breast cancer. It is used to study the vascular characteristics of the tumor. Neoadjuvant chemotherapy is the standard modality of treatment in locally advanced breast cancer. Histological examination remains the gold standard to assess the chemotherapy response. However, based on the color Doppler findings, a new scoring system that could predict histological response following chemotherapy is proposed. Methods Fifty cases of locally advanced infiltrating duct carcinoma of the breast were studied. The mean age of the patients was 44.5 years. All patients underwent clinical, Doppler and histopathological assessment followed by three cycles of CAF (Cyclophosphamide, Adriamycin and 5-Fluorouracil) chemotherapy, repeat clinical and Doppler examination and surgery. The resected specimens were examined histopathologically and histological response was correlated with Doppler findings. The Doppler characteristics of the tumor were graded as 1–4 for 50% and complete disappearance of flow signals respectively. A cumulative score was calculated and compared with histopathological response. Results were analyzed using Chi square test, sensitivity, specificity, positive and negative predictive values. Results The maximum Doppler score according to the proposed scoring system was twelve and minimum three. Higher scores corresponded with a more favorable histopathological response. Twenty four patients had complete response to chemotherapy. Sixteen of these 24 patients (66.7%) had a cumulative Doppler score more than nine. The sensitivity of cumulative score >5 was 91.7% and specificity was 38.5%. The area under the ROC curve of the cumulative score >9 was 0.72. Conclusion Doppler scoring can be accurately used to objectively predict the response to chemotherapy in patients with locally advanced breast cancer and it correlates well with histopathological response. PMID:17725837

  19. 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.

  20. 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

  1. 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.

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

    Directory of Open Access Journals (Sweden)

    Elizabeth Trice Loggers

    2016-01-01

    Full Text Available 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.

  3. TU-AB-204-04: Advances in CBCT for Breast Imaging

    Energy Technology Data Exchange (ETDEWEB)

    Boone, J. [University of California Davis School of Medicine (United States)

    2015-06-15

    assessment of novel therapies. Finally, Dr. J. Boone (UC Davis) will present on the topic: Advances in CBCT for Breast Imaging. Breast CT has been studied as an imaging tool for diagnostic breast evaluation and for potential breast cancer screening. The breast CT application lends itself to CBCT because of the small dimensions of the breast, the tapered shape of the breast towards higher cone angle, and the fact that there are no bones in the breast. The performance of various generations of breast CT scanners developed in recent years will be discussed, focusing on advances in spatial resolution and image noise characteristics. The results will also demonstrate the results of clinical trials using both computer and human observers. Learning Objectives: Understand the challenges, key technological advances, and emerging opportunities of CBCT in: Brain perfusion imaging, including assessment of ischemic stroke Cardiac imaging for functional assessment in cardiac interventions Orthopedics imaging for evaluation of musculoskeletal trauma, arthritis, and osteoporosis Breast imaging for screening and diagnosis of breast cancer. Work presented in this symposium includes research support by: Siemens Healthcare (Dr. Chen); NIH and Siemens Healthcare (Dr. Fahrig); NIH and Carestream Health (Dr. Zbijewski); and NIH (Dr. Boone)

  4. Reproducibility of Digital PCR Assays for Circulating Tumor DNA Analysis in Advanced Breast Cancer

    Science.gov (United States)

    Hrebien, Sarah; O’Leary, Ben; Beaney, Matthew; Schiavon, Gaia; Fribbens, Charlotte; Bhambra, Amarjit; Johnson, Richard; Turner, Nicholas

    2016-01-01

    Circulating tumor DNA (ctDNA) analysis has the potential to allow non-invasive analysis of tumor mutations in advanced cancer. In this study we assessed the reproducibility of digital PCR (dPCR) assays of circulating tumor DNA in a cohort of patients with advanced breast cancer and assessed delayed plasma processing using cell free DNA preservative tubes. We recruited a cohort of 96 paired samples from 71 women with advanced breast cancer who had paired blood samples processed either immediately or delayed in preservative tubes with processing 48–72 hours after collection. Plasma DNA was analysed with multiplex digital PCR (mdPCR) assays for hotspot mutations in PIK3CA, ESR1 and ERBB2, and for AKT1 E17K. There was 94.8% (91/96) agreement in mutation calling between immediate and delayed processed tubes, kappa 0.88 95% CI 0.77–0.98). Discordance in mutation calling resulted from low allele frequency and likely stochastic effects. In concordant samples there was high correlation in mutant copies per ml plasma (r2 = 0.98; pprocessed tubes, although overall quantification of total cell free plasma DNA had similar prognostic effects in immediate (HR 3.6) and delayed (HR 3.0) tubes. There was moderate agreement in changes in allele fraction between sequential samples in quantitative mutation tracking (r = 0.84, p = 0.0002). Delayed processing of samples using preservative tubes allows for centralized ctDNA digital PCR mutation screening in advanced breast cancer. The potential of preservative tubes in quantitative mutation tracking requires further research. PMID:27760227

  5. Percutaneous renal tumour biopsy.

    Science.gov (United States)

    Delahunt, Brett; Samaratunga, Hemamali; Martignoni, Guido; Srigley, John R; Evans, Andrew J; Brunelli, Matteo

    2014-09-01

    The use of percutaneous renal tumour biopsy (RTB) as a diagnostic tool for the histological characterization of renal masses has increased dramatically within the last 30 years. This increased utilization has paralleled advances in imaging techniques and an evolving knowledge of the clinical value of nephron sparing surgery. Improved biopsy techniques using image guidance, coupled with the use of smaller gauge needles has led to a decrease in complication rates. Reports from series containing a large number of cases have shown the non-diagnostic rate of RTB to range from 4% to 21%. Re-biopsy has been shown to reduce this rate, while the use of molecular markers further improves diagnostic sensitivity. In parallel with refinements of the biopsy procedure, there has been a rapid expansion in our understanding of the complexity of renal cell neoplasia. The 2013 Vancouver Classification is the current classification for renal tumours, and contains five additional entities recognized as novel forms of renal malignancy. The diagnosis of tumour morphotype on RTB is usually achievable on routine histology; however, immunohistochemical studies may be of assistance in difficult cases. The morphology of the main tumour subtypes, based upon the Vancouver Classification, is described and differentiating features are discussed.

  6. National consensus in China on diagnosis and treatment of patients with advanced breast cancer

    Science.gov (United States)

    Hu, Xichun; Jiang, Zefei; Li, Huiping; Chen, Jiayi; Cui, Shude; Li, Qing; Liao, Ning; Liu, Donggeng; Liu, Jian; Lu, Jinsong; Shen, Kunwei; Sun, Tao; Teng, Yuee; Tong, Zhongsheng; Wang, Shulian; Wang, Xiang; Wang, Xiaojia; Wang, Yongsheng; Wu, Jiong; Yuan, Peng; Zhang, Pin; Zhang, Qingyuan; Zheng, Hong; Pang, Da; Ren, Guosheng; Shao, Zhimin; Shen, Zhenzhou; Song, Erwei; Song, Santai

    2015-01-01

    The recently available guidelines on the management of advanced breast cancer (ABC) organized by Chinese Anti-Cancer Association, Committee of Breast Cancer Society (CACA-CBCS) do not elucidate ABC in details. To instruct clinicians in treatment of ABC, a Chinese expert consensus meeting on diagnosis and treatment of ABC was held in June 2014 and a consensus is developed. The following consensus provides the level of evidence and supporting documents for each recommendation, and introduces research topics to be urgently addressed. Notably, the consensus on diagnosis and treatment of ABC in China is developed to be applied nationwide. In different areas, multidisciplinary treatment (MDT) tailored to the each patient and the disease itself should be applied based on the basic principles of modern oncology. PMID:26605288

  7. Different response to neoadjuvant chemotherapy for different molecular subtypes in patients with locally advanced breast cancer

    Institute of Scientific and Technical Information of China (English)

    Huafeng Kang; Zhijun Dai; Xiaobin Ma; Xing Bao; Shuai Lin; Hongbing Ma; Xiaoxu Liu; Xijing Wang

    2013-01-01

    Objective: The aim of this study was to evaluate the impact of different molecular subtypes defined by immunohistochemistry (IHC) staining on the response rate for patients with locally advanced breast cancer received neoadjuvant chemotherapy. Methods: One hundred and seven breast cancer patients admitted from 2007 to 2011 who received 4 cycles of docetaxel/epirubicin-combined (TE) neoadjuvant chemotherapy were retrospectively reviewed, the patients were classified into 4 subtypes: luminal A, luminal B, HER-2 and triple negative breast cancer (TNBC) according to different combination patterns of estrogen receptor (ER), progesterone receptor (PR) and human epidermal growth factor-2 (HER-2) expression defined by IHC method. The correlation between response rate and the molecular subtypes were analyzed. Results: The pathological complete response (PCR), clinical complete response (CCR), clinical partial response (CPR), and clinical stable disease (CSD) rate of whole group was 15.89% (17/107), 22.43% (24/107), 63.55% (68/107), 14.02% (15/107), respectively, and the overall response rate (ORR) was 85.98% (92/107). The PCR rate and ORR of luminal A, luminal B, HER-2 and TNBC subtypes was 4.76% and 73.81%; 16.67% and 83.33%;17.65% and 100.00%; 30.00% and 96.67%, respectively. The PCR and ORR rate of HER-2/TNBC subtypes was higher than that of luminal A/B subtypes (P = 0.019, P = 0.002, respectively). Conclusion: Different molecular subtypes display different response rate for patients with locally advanced breast cancer received neoadjuvant TE chemotherapy, HER-2/TNBC subtypes have a higher PCR and ORR rate than that of luminal A/B subtypes.

  8. Receptor for Advanced Glycation End Products (RAGE) as a Novel Target for Inhibiting Breast Cancer Bone Metastasis

    Science.gov (United States)

    2013-04-01

    generated for studying the role of mS100a7a15 in psoriasis (26). To determine the role of mS100a7a15 in tumor- igenesis, we generated an inducible...been proposed for hS100A7, its biologic role particularly in breast cancer remains to be defined. In this study, we characterized the tumor-enhancing...mediated depletion of tumour-associated macrophages: a new and highly effective antiangiogenic therapy approach. Br J Cancer 2006;95: 272–81. 22. Webb

  9. Clinical efficacy of breast-conserving surgery combined with neoadjuvant chemotherapy for locally advanced breast cancer: a report of 81 cases

    Directory of Open Access Journals (Sweden)

    Zhi-yu CAO

    2015-07-01

    Full Text Available Objective To investigate the clinical efficacy of neoadjuvant chemotherapy combined with breast-conserving surgery for locally advanced breast cancer. Methods Eighty-one patients with locally advanced breast cancer were selected from those who were admitted into 309 Hospital of PLA from January 2009 to October 2013, consisting of 65 patients in stage Ⅲa and 16 in stage Ⅲb, and they were treated with neoadjuvant chemotherapy combined with breast-conserving surgery. The clinical efficacy [complete response (CR, partial response (PR, stable disease (SD and progress disease (PD] was observed during follow-up. Results All the patients were followed-up for 12-60 months with a median of 34 months. There were 12 CR patients (14.8%, including 4 with pathological complete response (4.9%, and 52 PR patients (64.2%, 17 SD patients (21.0%. No PD was observed. The overall response rate(ORR was 79.0%(64/81. After follow-up for 12-60 months (median 34 months, distant metastasis to the lung, liver, meninges and bone occurred in 3 patients (3.7%, 3/81 and 1 of them died. Forty-eight patients received breastconserving surgery. The local recurrence rate was 6.3% (3/48. Assessment of cosmetic result was carried out in 48 patients who received breast-conserving surgery and comprehensive treatment for one year, and excellent results were obtained in 14.6% (7/48, good in 43.8% (21/48, and poor in 41.7% (20/48. Conclusions The therapeutic efficacy of locally advanced breast cancer is satisfactory by neoadjuvant chemotherapy and breast-conserving surgery. Standardization of excision and postoperative radiotherapy, systemic comprehensive treatment is the key to the success of the treatment. DOI: 10.11855/j.issn.0577-7402.2015.06.14

  10. 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.)

  11. 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.

  12. Skull base tumours

    Energy Technology Data Exchange (ETDEWEB)

    Borges, Alexandra [Instituto Portugues de Oncologia Francisco Gentil, Servico de Radiologia, Rua Professor Lima Basto, 1093 Lisboa Codex (Portugal)], E-mail: borgesalexandra@clix.pt

    2008-06-15

    With the advances of cross-sectional imaging radiologists gained an increasing responsibility in the management of patients with skull base pathology. As this anatomic area is hidden to clinical exam, surgeons and radiation oncologists have to rely on imaging studies to plan the most adequate treatment. To fulfil these endeavour radiologists need to be knowledgeable about skull base anatomy, about the main treatment options available, their indications and contra-indications and needs to be aware of the wide gamut of pathologies seen in this anatomic region. This article will provide a radiologists' friendly approach to the central skull base and will review the most common central skull base tumours and tumours intrinsic to the bony skull base.

  13. Stability of the HER2 gene after primary chemotherapy in advanced breast cancer.

    Science.gov (United States)

    Varga, Zsuzsanna; Caduff, Rosmarie; Pestalozzi, Bernhard

    2005-02-01

    We investigated whether alterations of the Her2 gene could be detected in breast cancer samples following primary chemotherapy in advanced breast cancer. The prospective study involved 23 patients with stage-II, -III or -IV breast cancer. All patients were treated with two to six cycles of fluorouracil-epirubicin and/or cyclophosphamid/epi-docetaxel. The Her2 protein and gene were assessed both on core needle biopsies prior to and on surgical specimens after completing chemotherapy using immunohistochemistry (IHC) and fluorescence in situ hybridization (FISH) methods. Estrogen and progesterone receptors (ER/PR) were also determined on both samples using IHC. Her2 status was modified in eight patients using IHC (35%) and in three patients using FISH (13%). Changes in ER/PR expression were detected in seven patients (30%). Our data suggest that alterations of the Her2 gene can occur, although not usually after primary or neoadjuvant chemotherapy. However, changes in ER/PR status seem to be a more common event; thus, both can lead to different therapeutic options. Intratumoral heterogeneity as well as sampling variations can contribute to modification of the Her2 status after primary chemotherapy.

  14. Two Cases of Mastectomy after Paclitaxel + Bevacizumab Therapy for Locally Advanced Breast Cancer

    Directory of Open Access Journals (Sweden)

    Chika Shinoda

    2014-05-01

    Full Text Available Introduction: Locally advanced breast cancer (LABC deteriorates the quality of life (QOL of the affected patients. Combination chemotherapy or extended chemotherapy is considered to help to shrink local lesions. Case 1: A 71-year-old female with a history of tympanitis and cystitis with methicillin-resistant Staphylococcus aureus (MRSA visited our hospital. There was a tumor of 7 cm in diameter in her right breast with skin ulceration. Paclitaxel + bevacizumab therapy was started, and after five cycles of therapy, a mastectomy with axillary dissection was performed. Chemotherapy with anthracycline was avoided for fear of activating the MRSA. After the operation, the patient's wound opened. However, it naturally epithelialized. Case 2: A 41-year-old female visited our hospital due to a tumor of 8 cm in diameter in her right breast with skin ulceration. Four cycles of paclitaxel + bevacizumab therapy were started, and her tumor almost disappeared during the first cycle. Then, doxorubicin + cyclophosphamide therapy was performed for four cycles, and a mastectomy with axillary dissection was performed. Her postoperative course was good. Discussion: Chemotherapy with bevacizumab or extended chemotherapy is generally not considered to contribute to a survival improvement. However, such therapy contributes in increasing the response to chemotherapy, and should be considered for patients with LABC to shrink the local lesions and improve the QOL.

  15. 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

  16. Gastric Calcifying Fibrous Tumour

    Directory of Open Access Journals (Sweden)

    Tan Attila

    2006-01-01

    Full Text Available Intramucosal gastric tumours are most commonly found to be gastrointestinal stromal tumours or leiomyomas (smooth muscle tumours; however, a variety of other uncommon mesenchymal tumours can occur in the stomach wall. A rare benign calcifying fibrous tumour is reported and the endoscopic appearance, ultrasound findings and morphology are documented. A review of the literature found only two similar cases.

  17. 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.

  18. Dosimetric evaluation of neutron capture therapy for local advanced breast cancer

    Energy Technology Data Exchange (ETDEWEB)

    Yanagie, H. [Department of Nuclear Engineering and Management, Graduate School of Engineering, University of Tokyo, Tokyo (Japan); Cooperative Unit of Medicine and Engineering, University of Tokyo Hospital, Tokyo (Japan)], E-mail: yanagie@n.t.u-tokyo.ac.jp; Kumada, H. [Japan Atomic Research Institute, Ibaraki (Japan); Sakurai, Y. [Research Reactor Institute, Kyoto University, Osaka (Japan); Nakamura, T. [Japan Atomic Research Institute, Ibaraki (Japan); Department of Nuclear Physics, Ibaraki University, Ibaraki (Japan); Furuya, Y. [Department of Surgery, Satukidai Hospital, Chiba (Japan); Sugiyama, H. [Cooperative Unit of Medicine and Engineering, University of Tokyo Hospital, Tokyo (Japan); Ono, K. [Research Reactor Institute, Kyoto University, Osaka (Japan); Takamoto, S. [Cooperative Unit of Medicine and Engineering, University of Tokyo Hospital, Tokyo (Japan); Department of Cardiac Surgery, University of Tokyo Hospital, Tokyo (Japan); Eriguchi, M. [Cooperative Unit of Medicine and Engineering, University of Tokyo Hospital, Tokyo (Japan); Department of Microbiology, Syowa University School of Pharmaceutical Sciences, Tokyo (Japan); Takahashi, H. [Department of Nuclear Engineering and Management, Graduate School of Engineering, University of Tokyo, Tokyo (Japan); Cooperative Unit of Medicine and Engineering, University of Tokyo Hospital, Tokyo (Japan)

    2009-07-15

    Local recurrence breast cancer is one of the most difficult conditions to cure and there is a need for new therapy. If sufficient boron compound can be targeted to the tumor, boron neutron capture therapy (BNCT) can be applied to local recurrent breast cancer. In this study, we performed a preliminary dosimetry with a phantom model of the mammary gland at Kyoto University Research Reactor (KUR), and a feasibility dosimetry with JAERI Computational Dosimetry System (JCDS) at JRR4 reactor of Japan Atomic Research Institute. We performed preliminary dosimetry of a phantom model of the mammary gland with thermal neutron irradiation (OO-0011 mode) on LiF collimation at KUR. The thermal neutron flux was 5.16 E+08 cm{sup -2} s{sup -1} at the surface of phantom. The blood boron concentration is estimated to be 30 ppm; tumor boron concentration is also estimated to be 90 ppm according to tumor/blood ratio 3 and skin/blood ratio 1.2. Tumor RBE dose is estimated to be 47 Gy/h, and skin RBE dose is 12.4 Gy/h. In case of advanced breast cancer, we performed the feasibility estimation of 3D construction of tumor according to the MRI imaging of a patient with epithermal neutron mode at JRR4. The blood boron concentration (ppm) and tumor/normal tissue ratio are estimated to be 24 and 3.5, respectively. Skin RBE dose is restricted to 10 Gy/h, the maximum tumor RBE dose, minimum tumor RBE dose, and mean tumor RBE dose are 42.2, 11.3, and 28.9 Gy-Eq, respectively, in half hour irradiation. In this study, we showed the possibility to apply BNCT to local recurrent breast cancer. We can irradiate tumors selectively and as safely as possible, reducing the effects on neighboring healthy tissues.

  19. Neoadjuvant Chemotherapy Creates Surgery Opportunities For Inoperable Locally Advanced Breast Cancer

    Science.gov (United States)

    Wang, Minghao; Hou, Lingmi; Chen, Maoshan; Zhou, Yan; Liang, Yueyang; Wang, Shushu; Jiang, Jun; Zhang, Yi

    2017-01-01

    Neoadjuvant chemotherapy (NAC), the systematic chemotherapy given to patients with locally advanced and inoperable breast caner, has been proven to be of great clinical values. Many scientific reports confirmed NAC could effectively eliminate sub-clinical disseminated lesions of tumor, and improve long-term and disease-free survival rate of patients with locally advanced breast cancer (LABC); however, up to now, LABC is still a serious clinical issue given improved screening and early diagnosis. This study, with main focus on inoperable LABC, investigated the values of NAC in converting inoperable LABC into operable status and assessed the prognosis. Sixty-one patients with inoperable LABC were initially treated with neoadjuvant chemotherapy; their local conditions were improved to operable status. Radical surgery was exerted on 49 patients. Original chemotherapy was performed after surgery, followed by local radiotherapy. And endocrine therapy was optional according to the hormone receptor status. The quality of life for most patients with skin diabrosis was obviously improved because their local conditions were under control. For all recruited cases, the survival duration and life quality were significantly improved in patients who finished both NAC and surgery compared to those who did not. Further more, this study demonstrates improved prognostic consequences.

  20. Living with Advanced Breast Cancer among Ghanaian Women: Emotional and Psychosocial Experiences

    Directory of Open Access Journals (Sweden)

    Adwoa Bemah Bonsu

    2014-01-01

    Full Text Available The purpose of this study was to explore the emotional and psychosocial experiences of Ghanaian women living with advanced breast cancer in the Kumasi metropolis. The study employed a qualitative exploratory descriptive design. Purposive sampling approach was used and data was saturated with 10 participants aged between 32 and 65 years. All interviews were audio-taped and transcribed. Data was analyzed concurrently based on the techniques of content analysis. Anonymity and confidentiality were ensured. Women experienced emotional reactions such as sadness, fear, and anxiety. Pain was severe and led to suicidal ideations. Women experienced lost hopes regarding their marriage, parenting, and work. They received support from their families, spouses, colleagues, health professionals, and spiritual leaders. Women coped by accepting the disease and surrendering to God and having the will to live. Five major themes described were emotional reactions, pain, lost hope, support, and coping. It was recommended that health care providers involved in breast cancer management should be trained to enhance effective and holistic care of women and their families. Also, patients with advanced disease should be given effective pain management and a multidisciplinary palliative care team should be instituted to care for the women.

  1. Impact of Diabetes and Hyperglycemia on Survival in Advanced Breast Cancer Patients

    Directory of Open Access Journals (Sweden)

    Cynthia Villarreal-Garza

    2012-01-01

    Full Text Available Purpose. We examined the impact of diabetes and hyperglycemia on cancer-specific survival of patients with metastatic or recurrent breast cancer (BC. Methods. We performed a retrospective analysis of 265 patients with advanced BC receiving palliative chemotherapy. BC-specific mortality was compared for diabetic and nondiabetic patients as well as for patients that presented hyperglycemia during treatment. Results. No difference was observed between the diabetic and nondiabetic patients in terms of overall survival (OS. A difference in OS was observed between nondiabetic patients and diabetic patients who had hyperglycemia. The OS was greater in diabetic patients with proper metabolic control than diabetic patients with hyperglycemia. The risk of death was higher in patients with mean glucose levels >130 mg/dL during treatment. Several factors were associated with poor OS: tumor stage, hormone-receptor-negative tumors, HER2 negative disease, multiple metastatic sites, presence of visceral metastases, and mean glucose >130 mg/dL. Conclusion. Elevated glucose levels are associated with a poor outcome in diabetic and nondiabetic patients in contrast to patients with normoglycemic levels, conferring an elevated risk of death. According to these results, clinicians should monitor glucose levels during treatment for advanced breast cancer disease and take action to maintain normal glucose levels.

  2. Phase I study of tremelimumab (CP-675 206) plus PF-3512676 (CPG 7909) in patients with melanoma or advanced solid tumours

    Science.gov (United States)

    Millward, M; Underhill, C; Lobb, S; McBurnie, J; Meech, S J; Gomez-Navarro, J; Marshall, M A; Huang, B; Mather, C B

    2013-01-01

    Background: Tremelimumab, a fully human cytotoxic T-lymphocyte antigen 4 monoclonal antibody, and PF-3512676, a Toll-like receptor-9 agonist, are targeted immune modulators that elicit durable single-agent antitumour activity in advanced cancer. Methods: To determine the maximum tolerated dose (MTD) of these agents combined during this phase I study, patients received intravenous tremelimumab (6.0, 10.0, or 15.0 mg kg−1) every 12 weeks plus subcutaneous PF-3512676 (0.05, 0.10, or 0.15 mg kg−1) weekly. Primary end points were safety and tolerability; secondary end points included pharmacokinetics and antitumour activity. Results: Twenty-one patients with stage IV melanoma (n=17) or advanced solid tumours (n=4) were enrolled. Injection-site reactions (n=21; 100%), influenza-like illness (n=18; 86%), and diarrhoea (n=13; 62%) were the most common treatment-related adverse events (TAEs). Grade ⩾3 TAEs were reported (n=7; 33%). Dose-limiting toxicities (prespecified 6-week observation) occurred in one of the six patients in the 10 mg kg−1 tremelimumab plus 0.05 mg kg−1 PF-3512676 cohort (grade 3 hypothalamopituitary disorder) and two of the six patients in the 15 mg kg−1 tremelimumab plus 0.05 mg kg−1 PF-3512676 cohort (grade 3 diarrhoea). Consequently, 15 mg kg−1 tremelimumab plus 0.05 mg kg−1 PF-3512676 exceeded the MTD. Two melanoma patients achieved durable (⩾170 days) partial response. No human antihuman antibody responses to tremelimumab were observed. Conclusion: Weekly PF-3512676 (⩽0.15 mg kg−1) plus tremelimumab (⩽10 mg kg−1 every 12 weeks) was tolerable. PMID:23652314

  3. Pre-diagnostic smoking behaviour and poorer prognosis in a German breast cancer patient cohort - Differential effects by tumour subtype, NAT2 status, BMI and alcohol intake

    NARCIS (Netherlands)

    Seibold, P.; Vrieling, A.; Heinz, J.; Obi, N.; Sinn, H.P.; Flesch-Janys, D.; Chang-Claude, J.

    2014-01-01

    BACKGROUND: Inconsistent associations of smoking and breast cancer-specific mortality might be explained by subgroups of patients with different susceptibility to harmful effects of smoking. METHODS: We used a prospective cohort of 3340 postmenopausal breast cancer patients aged 50-74 and diagnosed

  4. 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).

  5. Primary radiotherapy after tumour excision as an alternative to mastectomy for early breast cancer. Rationale and preliminary results of a prospective study.

    Science.gov (United States)

    Browde, S; Nissenbaum, M M

    1983-09-28

    A conservative approach to the management of breast cancer is gaining acceptance. The evidence from many retrospective and prospective studies indicates that breast-preserving surgery and radiation therapy give results equal to those of mastectomy. Relapse affecting the breast alone has been shown not to be detrimental to survival, while the psychological benefits to the patients have been gratifying. A prospective study of early breast cancer treated by conservative surgery and radiation was commenced at the Johannesburg Hospital in 1980. The results in 57 patients are reported. So far there have been 2 cases of local recurrence. In the majority of cases satisfactory cosmetic results were achieved. It is considered that lumpectomy with axillary dissection to establish nodal status followed by irradiation is the treatment of choice for stage I and II carcinoma of the breast.

  6. 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.

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

    Science.gov (United States)

    Alvarado-Miranda, Alberto; Arrieta, Oscar; Gamboa-Vignolle, Carlos; Saavedra-Perez, David; Morales-Barrera, Rafael; Bargallo-Rocha, Enrique; Zinser-Sierra, Juan; Perez-Sanchez, Victor; Ramirez-Ugalde, Teresa; Lara-Medina, Fernando

    2009-01-01

    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. PMID:19591689

  8. 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.

  9. Relationship of Clinical and Pathologic Nodal Staging in Locally Advanced Breast Cancer: Current Controversies in Daily Practice?

    Science.gov (United States)

    De Felice, Francesca; Musio, Daniela; Bulzonetti, Nadia; Raffetto, Nicola; Tombolini, Vincenzo

    2014-01-01

    Systemic neo-adjuvant therapy plays a primary role in the management of locally advanced breast cancer. Without having any negative effect in overall survival, induction chemotherapy potentially assures a surgery approach in unresectable disease or a conservative treatment in technically resectable disease and acts on a well-vascularized tumor bed, without the modifications induced by surgery. A specific issue has a central function in the neo-adjuvant setting: lymph nodes status. It still represents one of the strongest predictors of long-term prognosis in breast cancer. The discussion of regional radiation therapy should be a matter of debate, especially in a pathological complete response. Currently, the indication for radiotherapy is based on the clinical stage before the surgery, even for the irradiation of the loco-regional lymph nodes. Regardless of pathological down-staging, radiation therapy is accepted as standard adjuvant treatment in locally advanced breast cancer. PMID:25247013

  10. 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.

  11. 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

  12. Bisphosphonate-related osteonecrosis of jaws in advanced stage breast cancer was detected from bone scan: a case report

    Science.gov (United States)

    Chirappapha, Prakasit; Thongjood, Thanaporn; Aroonroch, Rangsima

    2017-01-01

    Bisphosphonates (BPs) are indicated to treat skeletal-related events (SREs) for cancer patients with bone metastasis. We report a 79-year-old woman with advanced stage breast cancer with bone metastasis who was prescribed BPs (zoledronate), then developed osteonecrosis of jaw. We provide a brief review of the pathogenesis, diagnosis and treatment of this complication. PMID:28210558

  13. Review of hormone-based treatments in postmenopausal patients with advanced breast cancer focusing on aromatase inhibitors and fulvestrant

    DEFF Research Database (Denmark)

    Kümler, Iben; Knoop, Ann S; Jessing, Christina A R;

    2016-01-01

    . However, overall survival was not significantly increased. CONCLUSION: Conventional treatment with an aromatase inhibitor or fulvestrant may be an adequate treatment option for most patients with hormone receptor-positive advanced breast cancer. Mammalian target of rapamycin (mTOR) inhibition and cyclin...

  14. 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.)

  15. 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.

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

    Science.gov (United States)

    Li, Xiaosong; Hode, Tomas; Guerra, Maria C.; Ferrel, Gabriela L.; Nordquist, Robert E.; Chen, Wei R.

    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.

  17. Cancer early detection program based on awareness and clinical breast examination: Interim results from an urban community in Mumbai, India.

    Science.gov (United States)

    Gadgil, Anita; Sauvaget, Catherine; Roy, Nobhojit; Muwonge, Richard; Kantharia, Surita; Chakrabarty, Anuradha; Bantwal, Kanchan; Haldar, Indrani; Sankaranarayanan, Rengaswamy

    2017-02-01

    Indian women with breast cancer are usually diagnosed in advanced stages leading to poor survival. Improving breast awareness and increasing access to early diagnosis and adequate treatment has been advocated for breast cancer control. We implemented a program to increase awareness on breast cancer and access to its early detection in an occupational health care scheme in Mumbai, India. Breast awareness brochures were mailed annually between June 2013 and June 2016 to a cohort of 22,500 eligible women aged 30-69 years old receiving universal health care from an occupational health care scheme comprising of primary health centres and a referral secondary care hospital in Mumbai. Women with suspected breast cancers were provided with diagnostic investigations and treatment. Socio-demographic information and tumour characteristics were compared between the breast awareness pre-intervention period (Jan 2005-May 2013) and the breast awareness intervention period after four rounds of mailers (June 2013-June 2016). The proportion of women with early tumours and axillary lymph node negative cancers increased from 74% to 81% and 46% to 53% respectively, between the two periods. While the proportion of patients receiving breast conserving surgery increased from 39% to 51%, the proportion receiving chemotherapy decreased from 84% to 56%. Interim results following efforts to improve breast awareness and access to care in a cohort of women in an occupational health care scheme indicate early detection and more conservative treatment of breast cancers. Creating awareness and improving access to care may result in cancer down-staging.

  18. 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

  19. 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

  20. Influence of neoadjuvant chemotherapy on the microRNA and tumor-related indicators of patients with advanced breast cancer

    Institute of Scientific and Technical Information of China (English)

    Wen-Jiang Wang

    2015-01-01

    Objective:To evaluate the influence of neoadjuvant chemotherapy for the microRNA and tumor-related indicators of patients with advanced breast cancer.Methods: 120 cases of patients with advanced breast cancer were randomly divided into two groups, NC group and CC group, each group had 60 cases, and 60 cases of patients with benign breast disease and healthy volunteers in the same period were included as BC group and HC group. Then the plasma levels of miR-31, miR-200c, miR-205 and sIL-2R, IL-6, VEGF of all subjects were detected and compared.Results:The plasma levels of miR-31 and miR-205 of NC group and CC group before treatment were lower than BC group and HC group, while the miR-200c and sIL-2R, IL-6, VEGF were higher than BC group and HC group. The efficacy of treatment of advanced breast cancer patients was positively correlated to the plasma levels of miR-31, miR-205 expression, and negatively correlated to the plasma levels of miR-200c and sIL-2R, IL-6, VEGF. After 15, 45 days of chemotherapy, the plasma levels of miR-31, miR-205 expression of NC group were significantly higher than CC group, and miR-200c and sIL-2R, IL-6, VEGF were significantly lower than CC group. Conclusion:Neoadjuvant chemotherapy can effectively increase the plasma levels of miR-31, miR-205, and down the plasma levels of miR-200c and sIL-2R, IL-6, VEGF, will beneficial to improve the advanced breast cancer.

  1. Tumour banking: the Spanish design.

    Science.gov (United States)

    Morente, M M; de Alava, E; Fernandez, P L

    2007-01-01

    In the last decade the technical advances in high throughput techniques to analyze DNA, RNA and proteins have had a potential major impact on prevention, diagnosis, prognosis and treatment of many human diseases. Key pieces in this process, mainly thinking about the future, are tumour banks and tumour bank networks. To face these challenges, diverse suitable models and designs can be developed. The current article presents the development of a nationwide design of tumour banks in Spain based on a network of networks, specially focusing on its harmonization efforts mainly regarding technical procedures, ethical requirements, unified quality control policy and unique sample identification. We also describe our most important goals for the next years. This model does not correspond to a central tumour bank, but to a cooperative and coordinated network of national and regional networks. Independently from the network in which it is included, sample collections reside in their original institution, where it can be used for further clinical diagnosis, teaching and research activities of each independent hospital. The herein described 'network of networks' functional model could be useful for other countries and/or international tumour bank activities.

  2. 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

  3. Role of extrahepatic UDP-glucuronosyltransferase 1A1: advances in understanding breast milk-induced neonatal hyperbilirubinemia

    Science.gov (United States)

    Fujiwara, Ryoichi; Maruo, Yoshihiro; Chen, Shujuan; Tukey, Robert H.

    2015-01-01

    Newborns commonly develop physiological hyperbilirubinemia (also known as jaundice). With increased bilirubin levels being observed in breast-fed infants, breast-feeding has been recognized as a contributing factor for the development of neonatal hyperbilirubinemia. Bilirubin undergoes selective metabolism by UDP-glucuronosyltransferase (UGT) 1A1 and becomes a water soluble glucuronide. Although several factors such as gestational age, dehydration and weight loss, and increased enterohepatic circulation have been associated with breast milk-induced jaundice (BMJ), deficiency in UGT1A1 expression is a known cause of BMJ. It is currently believed that unconjugated bilirubin is metabolized mainly in the liver. However, recent findings support the concept that extrahepatic tissues, such as small intestine and skin, contribute to bilirubin glucuronidation during the neonatal period. We will review the recent advances made towards understanding biological and molecular events impacting BMJ, especially regarding the role of extrahepatic UGT1A1 expression. PMID:26342858

  4. 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

  5. Ethical issues in autologous stem cell transplantation (ASCT in advanced breast cancer: A systematic literature review

    Directory of Open Access Journals (Sweden)

    Scheibler Fueloep

    2011-04-01

    Full Text Available Abstract Background An effectiveness assessment on ASCT in locally advanced and metastatic breast cancer identified serious ethical issues associated with this intervention. Our objective was to systematically review these aspects by means of a literature analysis. Methods We chose the reflexive Socratic approach as the review method using Hofmann's question list, conducted a comprehensive literature search in biomedical, psychological and ethics bibliographic databases and screened the resulting hits in a 2-step selection process. Relevant arguments were assembled from the included articles, and were assessed and assigned to the question list. Hofmann's questions were addressed by synthesizing these arguments. Results Of the identified 879 documents 102 included arguments related to one or more questions from Hofmann's question list. The most important ethical issues were the implementation of ASCT in clinical practice on the basis of phase-II trials in the 1990s and the publication of falsified data in the first randomized controlled trials (Bezwoda fraud, which caused significant negative effects on recruiting patients for further clinical trials and the doctor-patient relationship. Recent meta-analyses report a marginal effect in prolonging disease-free survival, accompanied by severe harms, including death. ASCT in breast cancer remains a stigmatized technology. Reported health-related-quality-of-life data are often at high risk of bias in favor of the survivors. Furthermore little attention has been paid to those patients who were dying. Conclusions The questions were addressed in different degrees of completeness. All arguments were assignable to the questions. The central ethical dimensions of ASCT could be discussed by reviewing the published literature.

  6. Self-Management and Transitions in Women With Advanced Breast Cancer

    Science.gov (United States)

    Schulman-Green, Dena; Bradley, Elizabeth H.; Knobf, M. Tish; Prigerson, Holly; DiGiovanna, Michael P.; McCorkle, Ruth

    2011-01-01

    Context Self-management involves behaviors that individuals perform to handle health conditions. Self-management may be particularly challenging during transitions—shifts from one life phase or status to another, for example, from cure- to noncure-oriented cared—because they can be disruptive and stressful. Little is known about individuals’ experiences with self-management, especially during transitions. Objectives Our purpose was to describe experiences of self-management in the context of transitions among women with advanced breast cancer. Methods We interviewed a purposive sample of 15 women with metastatic breast cancer about their self-management preferences, practices, and experiences, including how they managed transitions. Interviews were recorded and transcribed. The qualitative method of interpretive description was used to code and analyze the data. Results Participants’ mean age was 52 years (range 37–91 years); most were White (80%), married (80%), and college educated (60%). Self-management practices related to womens’ health and to communication with loved ones and providers. Participants expressed a range of preferences for participation in self-management. Self-management included developing skills, becoming empowered, and creating supportive networks. Barriers to self-management included symptom distress, difficulty obtaining information, and lack of knowledge about the cancer trajectory. Women identified transitions as shifts in physical, emotional, and social well-being, as when their cancer progressed and there was a need to change therapy. Transitions often prompted changes in how actively women self-managed and were experienced as positive, negative, and neutral. Conclusion Self-management preferences can vary. Providers should explore and revisit patients’ preferences and ability to self-manage over time, particularly during transitions. PMID:21444183

  7. 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.

  8. Advanced Researches of Phyllodes Tumour Related Biomarkers%乳腺叶状肿瘤相关生物学标志物研究进展

    Institute of Scientific and Technical Information of China (English)

    李萍

    2011-01-01

    乳腺叶状肿瘤(PT)是一组与纤维腺瘤(FA)类似的局限性双相性肿瘤.目前在临床诊断上面临的问题主要有两个方面:一是没有明确的标准将其与FA相区分;二是对于不同恶化程度的PT的界定还比较困难,只能采取局部扩大切除治疗.解决上述问题的关键是需要找到区分FA和PT,以及不同分化程度的PT的特异标志物,仅靠传统的影像学和细胞学检查难以做到.免疫组织化学结合现代分子生物学技术筛选到了多个相关的生物学标志物,为PT的诊断提供了强有力的依据.%Phyllodes tumor( PT) of the breast is a kind of limited and diphasic tumor,which is similar to fibroadenoma.There are two major problems we art- facing therapeutically: one that makes a distinction between PT and fibroadenoma(FA) ,the other is to differentiate phyllodes tumor grades.The key to resolve problems described above is finding biomarkers between PT and FA, also between different PT grades, which can not achieve just depend on traditional iconography and cytology examination.Many biomarkers have been found through immunohistochemistry combined with modern molecule biotechnology that lay a foundation of PT diagnosis and therapy.This article reviews advanced researches of PT related biomarkers.

  9. TU-EF-207-03: Advances in Stationary Breast Tomosynthesis Using Distributed X-Ray Sources

    Energy Technology Data Exchange (ETDEWEB)

    Zhou, O. [The University of North Carolina at Chapel Hill (United States)

    2015-06-15

    Breast imaging technology is advancing on several fronts. In digital mammography, the major technological trend has been on optimization of approaches for performing combined mammography and tomosynthesis using the same system. In parallel, photon-counting slot-scan mammography is now in clinical use and more efforts are directed towards further development of this approach for spectral imaging. Spectral imaging refers to simultaneous acquisition of two or more energy-windowed images. Depending on the detector and associated electronics, there are a number of ways this can be accomplished. Spectral mammography using photon-counting detectors can suppress electronic noise and importantly, it enables decomposition of the image into various material compositions of interest facilitating quantitative imaging. Spectral imaging can be particularly important in intravenously injected contrast mammography and eventually tomosynthesis. The various approaches and applications of spectral mammography are discussed. Digital breast tomosynthesis relies on the mechanical movement of the x-ray tube to acquire a number of projections in a predefined arc, typically from 9 to 25 projections over a scan angle of +/−7.5 to 25 degrees depending on the particular system. The mechanical x-ray tube motion requires relatively long acquisition time, typically between 3.7 to 25 seconds depending on the system. Moreover, mechanical scanning may have an effect on the spatial resolution due to internal x-ray filament or external mechanical vibrations. New x-ray source arrays have been developed and they are aimed at replacing the scanned x-ray tube for improved acquisition time and potentially for higher spatial resolution. The potential advantages and challenges of this approach are described. Combination of digital mammography and tomosynthesis in a single system places increased demands on certain functional aspects of the detector and overall performance, particularly in the tomosynthesis

  10. SEOM guidelines for the treatment of bone metastases from solid tumours.

    Science.gov (United States)

    Cassinello Espinosa, Javier; González Del Alba Baamonde, Aránzazu; Rivera Herrero, Fernando; Holgado Martín, Esther

    2012-07-01

    Bone metastases are a common and distressing effect of cancer, being a major cause of morbidity in many patients with advanced stage cancer, in particular in breast and prostate cancer. Patients with bone metastases can experience complications known as skeletal-related events (SREs) which may cause significant debilitation and have a negative impact on quality of life and functional independence. The current recommended systemic treatment for the prevention of SREs is based on the use of bisphosphonates: ibandronate, pamidronate and zoledronic acid- the most potent one- are approved in advanced breast cancer with bone metastases, whereas only zoledronic acid is indicated in advanced prostate cancer with bone metastases. The 2011 ASCO guidelines on breast cancer, recommend initiating bisphosphonate treatment only for patients with evidence of bone destruction due to bone metastases. Denosumab, a fully human antibody that specifically targets the RANK-L, has been demonstrated in two phase III studies to be superior to zoledronic acid in preventing or delaying SREs in breast and prostate cancer and non-inferior in other solid tumours and mieloma; it's convenient subcutaneous administration and the fact that does not require dose adjustment in cases of renal impairment, make this agent an attractive new therapeutic option in patients with bone metastases. Finally, in a phase III study against placebo, denosumab significantly increased the median metastasis-free survival in high risk non-metastatic prostate cancer, arising the potential role of these bone-modifying agents in preventing or delaying the development of bone metastases.

  11. Biodistribution and pharmacokinetics of In-111-labeled Stealth{reg_sign} liposomes in patients with solid tumours

    Energy Technology Data Exchange (ETDEWEB)

    Harrington, K.J.; Peters, A.M.; Mohammadtaghi, S. [Hammersmith Hospital, London (United Kingdom)] [and others

    1996-05-01

    The use of liposomal doxorubicin yields response rates of up to 70-80% in patients with AIDS-related Kaposi`s sarcoma with favourable alteration of the toxicity profile of the drug. Liposomal delivery of therapy in patients with solid cancers is currently under investigation. Our aim is to determine the biodistribution and pharmacokinetics of In-111-labeled Stealth{reg_sign} liposomes (SEQUUS{trademark}) liposomes (SEQUUS{trademark} Pharmaceuticals Inc., Menlo Park, USA) in patients with advanced solid malignant tumours. Ten patients (4 male, 6 female) with a median age of 59 (range 43 - 75) received 100 MBq of In-111-labeled Stealth{reg_sign} liposomes. Four had breast cancer, 3 head and neck tumours, 2 lung and 1 cervical cancer. Blood samples and whole body gamma camera images were obtained at 0.5, 4, 24, 48, 72, 96 and 240 hours after injection and sequential 24 hour urine collections were performed for the first 96 h. SPECT imaging was performed when indicated. High definition images of tumours were obtained in 9 patients (3/4 breast, 3/3 head and neck, 2/2 lung and 1/1 cervix cancers). One patient (breast cancer) had negative images. The median cumulative urinary excretion of In-111 over the first 96 h was 17.8 (range 3.5-21.3) % of the injected dose. The uptake of liposomes in various tissues was estimated from regions of interest on the whole body images. Prominent uptake was seen in the liver (10-15% of injected dose), lungs (4-9%) and spleen (2-8%). Tumour uptake in the first 96 h varied form 0.5-4% of the injected dose. This is approximately 10 fold higher than might be expected from experience with other targeting methods (eg monoclonal antibodies). These data confirm that Stealth liposomes have a prolonged circulation half-life and localise to solid tumour tissue.

  12. 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.

  13. 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

  14. Economic evaluation of fulvestrant as an extra step in the treatment sequence for ER-positive advanced breast cancer

    OpenAIRE

    Cameron, D. A.; Camidge, D R; Oyee, J; Hirsch, M.

    2008-01-01

    Drug therapies for advanced breast cancer in hormone-receptor-positive disease include both hormonal and chemotherapies. Current UK practice is to minimise toxicity by using sequential hormonal agents for as long as clinically appropriate. A Markov model was developed to investigate the cost effectiveness of different sequences of therapies, particularly exploring the effects of adding an additional hormonal agent, fulvestrant, to the treatment pathway. A systematic review was undertaken and ...

  15. Targeting tumour Cell Plasticity

    Institute of Scientific and Technical Information of China (English)

    Elizabeth D. WILLIAMS

    2009-01-01

    @@ Her research is focused on understanding the mechanisms of tumour progression and metastasis, particularly in uro-logical carcinomas (bladder and prostate). Tumour cell plasticity, including epithelial-mesenchymal transition, is a cen-tral theme in Dr Williams' work.

  16. Endocrinological and clinical evaluation of two doses of formestane in advanced breast cancer.

    Science.gov (United States)

    Bajetta, E.; Zilembo, N.; Buzzoni, R.; Noberasco, C.; Di Leo, A.; Bartoli, C.; Merson, M.; Sacchini, V.; Moglia, D.; Celio, L.

    1994-01-01

    Formestane is a selective inhibitor of oestrogen synthesis by aromatase enzymes and induces disease regression in breast cancer patients. This phase II randomised study was carried out to determine whether there were any differences in the effects of two different doses of formestane on oestradiol (E2) serum levels and to evaluate the corresponding clinical activity in post-menopausal patients with positive or unknown oestrogen receptor status pretreated or not for advanced disease. Furthermore, possible drug interference with adrenal steroidogenesis was assessed by measuring 17-hydroxycorticosteroid (17-OHCS) urinary levels. A total of 143 patients entered the study and were randomly assigned to receive formestane 250 mg (72 patients) or formestane 500 mg (71 patients), both given i.m. every 2 weeks. In comparison with baseline, E2 serum levels decreased by an average of 40% after only 15 days and remained unchanged thereafter, with no difference being observed between the two doses. The values of 17-OHCS remained unchanged during treatment in both groups. Objective responses were 28% (19/69) in the 250 mg and 46% (31/68) in the 500 mg group. In conclusion, the two formestane doses were equally effective in reducing E2 levels without affecting adrenal function, and in inducing a considerable percentage of clinical responses. PMID:8018527

  17. Rapid tumor necrosis and massive hemorrhage induced by bevacizumab and paclitaxel combination therapy in a case of advanced breast cancer

    Directory of Open Access Journals (Sweden)

    Ono M

    2013-10-01

    Full Text Available Mayu Ono, Tokiko Ito, Toshiharu Kanai, Koichi Murayama, Hiroshi Koyama, Kazuma Maeno, Yasuhiro Mochizuki, Asumi Iesato, Toru Hanamura, Toshihiro Okada, Takayuki Watanabe, Ken-ichi ItoDivision of Breast and Endocrine Surgery, Department of Surgery (II, Shinshu University School of Medicine, Matsumoto, JapanAbstract: Bevacizumab when combined with chemotherapy exerts significant activity against many solid tumors through tumor angiogenesis inhibition; however, it can induce severe side effects. We report the rare case of a 27-year-old premenopausal woman with locally advanced breast cancer that was marked by rapid tumor necrosis followed by massive hemorrhage shortly after bevacizumab and paclitaxel administration. On the basis of histopathological examination of a biopsy specimen and computed tomography findings, she was diagnosed with stage IV estrogen and progesterone receptor-negative and human epidermal growth factor receptor type 2-positive breast cancer with multiple organ metastases when she had entered gestational week 24. Cyclophosphamide, Adriamycin®, fluorouracil therapy was initiated, but multiple liver metastases continued to progress. A healthy fetus was delivered by induced delivery and trastuzumab-based treatment was initiated. Although the multiple liver metastases were controlled successfully by trastuzumab combined with paclitaxel, the primary tumor continued to expand even after subsequent administration of three other treatment regimens including anti-human epidermal growth factor receptor type 2 agents and cytotoxic drugs. To inhibit primary tumor growth, a combination therapy with paclitaxel and bevacizumab was subsequently initiated. Following therapy initiation, however, the large tumor occupying the patient's entire left breast became necrotic and ulcerated rapidly. Furthermore, massive hemorrhage from the tumor occurred 5 weeks after bevacizumab-based therapy initiation. Although hemostasis was achieved by manual

  18. 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

  19. Primary brain tumours in adults.

    Science.gov (United States)

    Ricard, Damien; Idbaih, Ahmed; Ducray, François; Lahutte, Marion; Hoang-Xuan, Khê; Delattre, Jean-Yves

    2012-05-26

    Important advances have been made in the understanding and management of adult gliomas and primary CNS lymphomas--the two most common primary brain tumours. Progress in imaging has led to a better analysis of the nature and grade of these tumours. Findings from large phase 3 studies have yielded some standard treatments for gliomas, and have confirmed the prognostic value of specific molecular alterations. High-throughput methods that enable genome-wide analysis of tumours have improved the knowledge of tumour biology, which should lead to a better classification of gliomas and pave the way for so-called targeted therapy trials. Primary CNS lymphomas are a group of rare non-Hodgkin lymphomas. High-dose methotrexate-based regimens increase survival, but the standards of care and the place of whole-brain radiotherapy remain unclear, and are likely to depend on the age of the patient. The focus now is on the development of new polychemotherapy regimens to reduce or defer whole-brain radiotherapy and its delayed complications.

  20. The genomic landscape of breast cancer and its interaction with host immunity.

    Science.gov (United States)

    Luen, Stephen; Virassamy, Balaji; Savas, Peter; Salgado, Roberto; Loi, Sherene

    2016-10-01

    Molecular profiling of thousands of primary breast cancers has uncovered remarkable genomic diversity between breast cancer subtypes, and even within subtypes. Only a few driver genes are recurrently altered at high frequency highlighting great challenges for precision medicine. Considerable evidence also confirms the role of host immunosurveillance in influencing response to therapy and prognosis in HER2+ and triple negative breast cancer. The role of immunosurveillance in ER + disease remains unclear. Advances in both these fields have lead to intensified interest in the interaction between genomic landscapes and host anti-tumour immune responses in breast cancer. In this review, we discuss the potential genomic determinants of host anti-tumour immunity - mutational load, driver alterations, mutational processes and neoantigens - and their relationship with immunity in breast cancer. Significant differences exist in both the genomic and immune characteristics amongst breast cancer subtypes. While ER + disease appears to be less immunogenic than HER2+ and triple negative breast cancer, it displays the greatest degree of heterogeneity. Mutational and neoantigen load appears to incompletely explains immune responses in breast cancer. Driver alterations do not appear to increase immunogenicity. Instead, they could contribute to immune-evasion or an immunosuppressive microenvironment, and therefore represent potential therapeutic targets. Finally, we also discuss the tailoring of immunotherapeutic strategies by genomic alterations, with possible multimodal combination approaches to maximise clinical benefits.

  1. Specific siRNA Targeting Receptor for Advanced Glycation End Products (RAGE Decreases Proliferation in Human Breast Cancer Cell Lines

    Directory of Open Access Journals (Sweden)

    Sheng Liu

    2013-04-01

    Full Text Available Receptor for Advanced Glycation End Products (RAGE is an oncogenic trans-membranous receptor overexpressed in various human cancers. However, the role of RAGE in breast cancer development and proliferation is still unclear. In this study, we demonstrated that RAGE expression levels are correlated to the degree of severity of breast cancer. Furthermore, there is a decrease in the proliferation of all sub-types of breast cancer, MCF-7, SK-Br-3 and MDA-MB-231, as a result of the effect of RAGE siRNA. RAGE siRNA arrested cells in the G1 phase and inhibited DNA synthesis (p < 0.05. Moreover, qRT-PCR and Western Blot results demonstrated that RAGE siRNA decreases the expression of transcriptional factor NF-κB p65 as well as the expression of cell proliferation markers PCNA and cyclinD1. RAGE and RAGE ligands can thus be considered as possible targets for breast cancer management and therapy.

  2. 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

  3. 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...

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

    Science.gov (United States)

    Farquharson, M J; Geraki, K; Falkenberg, G; Leek, R; Harris, A

    2007-02-01

    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 microm thick each. The data were obtained using a synchrotron X-ray fluorescence microprobe system. The spatial resolution of elemental maps was approximately 20 microm. 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.

  5. Response monitoring using quantitative ultrasound methods and supervised dictionary learning in locally advanced breast cancer

    Science.gov (United States)

    Gangeh, Mehrdad J.; Fung, Brandon; Tadayyon, Hadi; Tran, William T.; Czarnota, Gregory J.

    2016-03-01

    A non-invasive computer-aided-theragnosis (CAT) system was developed for the early assessment of responses to neoadjuvant chemotherapy in patients with locally advanced breast cancer. The CAT system was based on quantitative ultrasound spectroscopy methods comprising several modules including feature extraction, a metric to measure the dissimilarity between "pre-" and "mid-treatment" scans, and a supervised learning algorithm for the classification of patients to responders/non-responders. One major requirement for the successful design of a high-performance CAT system is to accurately measure the changes in parametric maps before treatment onset and during the course of treatment. To this end, a unified framework based on Hilbert-Schmidt independence criterion (HSIC) was used for the design of feature extraction from parametric maps and the dissimilarity measure between the "pre-" and "mid-treatment" scans. For the feature extraction, HSIC was used to design a supervised dictionary learning (SDL) method by maximizing the dependency between the scans taken from "pre-" and "mid-treatment" with "dummy labels" given to the scans. For the dissimilarity measure, an HSIC-based metric was employed to effectively measure the changes in parametric maps as an indication of treatment effectiveness. The HSIC-based feature extraction and dissimilarity measure used a kernel function to nonlinearly transform input vectors into a higher dimensional feature space and computed the population means in the new space, where enhanced group separability was ideally obtained. The results of the classification using the developed CAT system indicated an improvement of performance compared to a CAT system with basic features using histogram of intensity.

  6. Gemcitabine Plus Docetaxel Versus Docetaxel in Patients With Predominantly Human Epidermal Growth Factor Receptor 2-Negative Locally Advanced or Metastatic Breast Cancer: A Randomized, Phase III Study by the Danish Breast Cancer Cooperative Group

    DEFF Research Database (Denmark)

    Nielsen, Dorte L; Bjerre, Karsten D; Jakobsen, Erik H;

    2011-01-01

    PURPOSE The objective of this phase III study was to compare the efficacy of gemcitabine plus docetaxel (GD) versus docetaxel in patients with advanced breast cancer. PATIENTS AND METHODS Predominantly human epidermal growth factor receptor 2 (HER2) -negative patients were randomly assigned to ge...... GD compared with docetaxel demonstrated increased TTP in metastatic breast cancer. However, RR and OS were similar. Thus, the addition of gemcitabine failed to demonstrate any clinically meaningful benefit when combined with docetaxel....

  7. Recent advances reveal IL-8 signaling as a potential key to targeting breast cancer stem cells.

    Science.gov (United States)

    Singh, Jagdeep K; Simões, Bruno M; Howell, Sacha J; Farnie, Gillian; Clarke, Robert B

    2013-01-01

    Breast cancer stem-like cells (CSCs) are an important therapeutic target as they are purported to be responsible for tumor initiation, maintenance, metastases, and disease recurrence. Interleukin-8 (IL-8) is upregulated in breast cancer compared with normal breast tissue and is associated with poor prognosis. IL-8 is reported to promote breast cancer progression by increasing cell invasion, angiogenesis, and metastases and is upregulated in HER2-positive cancers. Recently, we and others have established that IL-8 via its cognate receptors, CXCR1 and CXCR2, is also involved in regulating breast CSC activity. Our work demonstrates that in metastatic breast CSCs, CXCR1/2 signals via transactivation of HER2. Given the importance of HER2 in breast cancer and in regulating CSC activity, a pathway driving the activation of these receptors would have important biological and clinical consequences, especially in tumors that express high levels of IL-8 and other CXCR1/2-activating ligands. Here, we review the IL-8 signaling pathway and the role of HER2 in maintaining an IL-8 inflammatory loop and discuss the potential of combining CXCR1/2 inhibitors with other treatments such as HER2-targeted therapy as a novel approach to eliminate CSCs and improve patient survival.

  8. Imaging of sacral tumours

    Energy Technology Data Exchange (ETDEWEB)

    Gerber, S.; Ollivier, L.; Brisse, H.; Neuenschwander, S. [Institut Curie, Department of Radiology, Paris (France); Leclere, J. [Institut Gustave Roussy, Department of Radiology, Villejuif (France); Vanel, D. [The Rizzoli Institute, Department of Radiology, Bologna (Italy); Missenard, G. [Institut Gustave Roussy, Comite de pathologie tumorale de l' appareil locomoteur, Villejuif (France); Pinieux, G. de [CHRU de Tours, Department of Pathology, Hopital Trousseau, Tours (France)

    2008-04-15

    All components of the sacrum (bone, cartilage, bone marrow, meninges, nerves, notochord remnants, etc.) can give rise to benign or malignant tumours. Bone metastases and intraosseous sites of haematological malignancies, lymphoma and multiple myeloma are the most frequent aetiologies, while primary bone tumours and meningeal or nerve tumours are less common. Some histological types have a predilection for the sacrum, especially chordoma and giant cell tumour. Clinical signs are usually minor, and sacral tumours are often discovered in the context of nerve root or pelvic organ compression. The roles of conventional radiology, CT and MRI are described and compared with the histological features of the main tumours. The impact of imaging on treatment decisions and follow-up is also reviewed. (orig.)

  9. Economic evaluation of fulvestrant as an extra step in the treatment sequence for ER-positive advanced breast cancer.

    Science.gov (United States)

    Cameron, D A; Camidge, D R; Oyee, J; Hirsch, M

    2008-12-16

    Drug therapies for advanced breast cancer in hormone-receptor-positive disease include both hormonal and chemotherapies. Current UK practice is to minimise toxicity by using sequential hormonal agents for as long as clinically appropriate. A Markov model was developed to investigate the cost effectiveness of different sequences of therapies, particularly exploring the effects of adding an additional hormonal agent, fulvestrant, to the treatment pathway. A systematic review was undertaken and a panel of seven UK oncologists validated assumptions used for treatment efficacy, treatment pathways and resources used. Fulvestrant was found to be a cost-effective treatment option when added to the treatment sequence as a second- or third-line hormonal therapy for advanced disease. For a cohort of 1000 patients, fulvestrant as a second-line hormone therapy provided an additional 47 life years and 41 quality-adjusted life years (QALYs), at an additional cost of pound 301 359. This equated to pound 6500 per life years gained and pound 7500 per QALY. When used as a third-line option, the fulvestrant arm was dominant providing an increase in health benefit of 27 QALYs for the whole cohort, at a mean overall cost reduction of pound 430 per patient. Sensitivity analyses showed these results to be robust, demonstrating that fulvestrant is an economically viable additional endocrine option in the United Kingdom for the treatment of hormone responsive advanced breast cancer.

  10. WE-FG-207A-00: Advances in Dedicated Breast CT.

    Science.gov (United States)

    Vedantham, Srinivasan; Molloi, Sabee

    2016-06-01

    Mammography-based screening has been a valuable imaging tool for the early detection of non-palpable lesions and has contributed to significant reduction in breast cancer associated mortality. However, the breast imaging community recognizes that mammography is not ideal, and in particular is inferior for women with dense breasts. Also, the 2-D projection of a 3-D organ results in tissue superposition contributing to false-positives. The sensitivity of mammography is breast-density dependent. Its sensitivity, especially in dense breasts, is low due to overlapping tissue and the fact that normal breast tissue, benign lesions and breast cancers all have similar "densities", making lesion detection more difficult. We ideally need 3-D imaging for imaging the 3-D breast. MRI is 3-D, whole breast ultrasound is 3-D, digital breast tomosynthesis is called 3-D but is really "pseudo 3-D" due to poor resolution along the depth-direction. Also, and importantly, we need to be able to administer intravenous contrast agents for optimal imaging, similar to other organ systems in the body. Dedicated breast CT allows for 3-D imaging of the uncompressed breast. In current designs, the patient is positioned prone on the table and the breast is pendant through an aperture and the scan takes approximately 10 seconds [O'Connell et al., AJR 195: 496-509, 2010]. Almost on the heels of the invention of CT itself, work began on the development of dedicated breast CT. These early breast CT systems were used in clinical trials and the results from comparative performance evaluation of breast CT and mammography for 1625 subjects were reported in 1980 [Chang et al., Cancer 46: 939-46, 1980]. However, the technological limitations at that time stymied clinical translation for decades. Subsequent to the landmark article in 2001 [Boone et al., Radiology 221: 657-67, 2001] that demonstrated the potential feasibility in terms of radiation dose, multiple research groups are actively investigating

  11. 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.

  12. Influencia del sitio de inoculación sobre el crecimiento, morfología y metástasis espontáneas del cáncer de mama en un modelo murino (Effect of tumour host microenvironment on growth, morphology and spontaneous metastases in a breast cancer mouse model

    Directory of Open Access Journals (Sweden)

    Fuentes-Morales, Dasha

    2009-02-01

    Full Text Available ResumenEl cáncer de mama constituye la principal neoplasia que se presenta en la mujer. Para el estudio de esta enfermedad se emplean frecuentemente modelos murinos, sin embargo el microambiente tisular del sitio de inoculación del tumor juega un papel fundamental en el posterior desarrollo de la neoformación y por tanto en los resultadosexperimentales. En este trabajo nos propusimos como objetivo determinar la influencia del sitio de inoculación sobre la morfología, crecimiento y metástasis espontáneas en un modelo murino de cáncer de mama. Para desarrollar nuestra investigación se utilizaron ratones BALB/c hembras jóvenes a las cuales se les inocularon células de F3II por vía subcutánea (ectópico y directamente en la glándula mamaria (ortotópico. Transcurridos 35 días se practicó la eutanasia y se estudiaron las características morfológicas y metástasis espontáneas de los tumores inoculados en su tejido de origen respecto a los que se implantaron en elsubcutis. Los resultados obtenidos evidenciaron semejanzas en la morfohistología y metástasis espontáneas cuando las células son inoculadas en la glándula mamaria o en el tejido celular subcutáneo, sin embargo se encontró una mayor velocidad de crecimiento en las células inoculadas por vía ortotópica respecto a los tumores inoculados en el subcutis. Los hallazgos realizados sugieren que la inyección del carcinoma F3II tanto por la vía ortotópica como por la subcutánea en ratones BALB/c permite obtener un modelo útil para el estudio del cáncer de mama.SummaryBreast cancer is the most frequently diagnosed cancer in women. Mousemodels of mammary cancer permit experimental evaluation of thebehavior and biology of disease, although tumour host icroenvironmentplays an important role in tumour development and therefore inexperimental results. In this study, we aimed to examine the influence of tumour host environment on tumour development and pathophysiology in

  13. The O-linked glycosylation of secretory/shed MUC1 from an advanced breast cancer patient's serum.

    Science.gov (United States)

    Storr, Sarah J; Royle, Louise; Chapman, Caroline J; Hamid, Umi M Abd; Robertson, John F; Murray, Andrea; Dwek, Raymond A; Rudd, Pauline M

    2008-06-01

    MUC1 is a high molecular weight glycoprotein that is overexpressed in breast cancer. Aberrant O-linked glycosylation of MUC1 in cancer has been implicated in disease progression. We investigated the O-linked glycosylation of MUC1 purified from the serum of an advanced breast cancer patient. O-Glycans were released by hydrazinolysis and analyzed by liquid chromatography-electrospray ionization-mass spectrometry and by high performance liquid chromatography coupled with sequential exoglycosidase digestions. Core 1 type glycans (83%) dominated the profile which also confirmed high levels of sialylation: 80% of the glycans were mono-, di- or trisialylated. Core 2 type structures contributed approximately 17% of the assigned glycans and the oncofoetal Thomsen-Friedenreich (TF) antigen (Galbeta1-3GalNAc) accounted for 14% of the total glycans. Interestingly, two core 1 type glycans were identified that had sialic acid alpha2-8 linked to sialylated core 1 type structures (9% of the total glycan pool). This is the first O-glycan analysis of MUC1 from the serum of a breast cancer patient; the results suggest that amongst the cell lines commonly used to express recombinant MUC1 the T47D cell line processes glycans that are most similar to patient-derived material.

  14. Surgical approach for ulcerated locally advanced breast cancer. A single Center experience: a retrospective study.

    Science.gov (United States)

    Laforgia, Rita; Punzo, Clelia; Panebianco, Annunziata; Volpi, Annalisa; Minafra, Marina; Sederino, Maria Grazia

    2017-01-12

    L’obiettivo del nostro studio è la valutazione della strategia chirurgica più idonea nei casi di LABC (Locally Advanced Breast Cancer) in condizioni di ulcerazione e sanguinamento. La diagnosi clinica del LABC prevede nella maggior parte dei casi una massa mammaria estesa associata ad edema, eritema, retrazione e sanguinamento, dolore, superficie cutanea irregolare e coinvolgimento linfonodale. L’intervento chirurgico di scelta per le forme T3-T4 è la mastectomia radicale che rappresenta un trattamento adeguato per il controllo locale della patologia. In caso di forme localmente avanzate e ulcerate, pur essendo forme inoperabili, l’exeresi chirurgica si rende necessaria per una bonifica locale. La presenza di fenomeni di ulcerazione e sanguinamento non rende possibile avviare un trattamento chemioterapico neoadiuvante ed è necessario eseguire interventi chirurgici palliativi. Il trattamento chirurgico stesso richiede mutilazioni ampie ed associate procedure di chirurgia plastica. Spesso per l’estensione della malattia ed il sovvertimento del corpus mammae durante l’exeresi chirurgica della mammella, la sezione su zone esenti da neoplasia non consente la chiusura immediata dei lembi. Abbiamo considerato, su un campione di 288 pazienti affette da carcinoma mammario, 11 donne con forme avanzate fra T4a e T4c (3.8%). E’ stata posta indicazione a trattamento chirurgico perché pazienti provenienti dal Pronto Soccorso con anemizzazione per neoplasie avanzate ulcerate e sanguinanti, non candidabili in prima istanza a chemioterapia neoadiuvante citoriduttiva. Le procedure adoperate per la ricostruzione della mammella sono state in 2 pazienti la rotazione di un lembo muscolo cutaneo, in 4 casi un innesto cutaneo prelevato dalla coscia, in 4 casi è stata utilizzata una matrice dermica biologica - sostituto cutaneo (INTEGRA) che è stata poi sostituita con un successivo innesto cutaneo a distanza di circa 20-30 giorni. Sono state osservate recidive in 2 casi

  15. Considerations for payers in managing hormone receptor-positive advanced breast cancer

    Directory of Open Access Journals (Sweden)

    Chitre M

    2014-07-01

    Full Text Available Mona Chitre,1 Kristen M Reimers21Pharmacy Management, Excellus BlueCross BlueShield, Rochester, NY, USA; 2Clinical Drug Programs, Magellan Health/Icore, Orlando, FL, USAAbstract: Breast cancer (BC is the second most common cause of death in women. In 2010, the direct cost associated with BC care in the US was $16.5 billion, the highest among all cancers. By the year 2020, at the current rates of incidence and survival, the cost is projected to increase to approximately $20 billion. Although endocrine therapies to manage hormone receptor-positive (HR+ BC are highly effective, endocrine resistance results in disease progression. Increased understanding of endocrine resistance and the mechanisms of disease progression has led to development and subsequent approval of novel targeted treatments, resulting in the expansion of the therapeutic armamentarium to combat HR+ BC. Clear guidelines based on the safety and efficacy of treatment options exist; however, the optimal sequence of therapy is unknown, and providers, payers, and other key players in the health care system are tasked with identifying cost-effective and evidence-based treatment strategies that will improve patient outcomes and, in time, help curb the staggering increase in cost associated with BC care. Safety and efficacy are key considerations, but there is also a need to consider the impact of a given therapy on patient quality of life, treatment adherence, and productivity. To minimize cost associated with overall management, cost-effectiveness, and financial burden that the therapy can impose on patients, caregivers and managed care plans are also important considerations. To help evaluate and identify the optimal choice of therapy for patients with HR+ advanced BC, the available data on endocrine therapies and novel agents are discussed, specifically with respect to the safety, efficacy, financial impact on patients and the managed care plan, impact on quality of life and

  16. Biochemistry of neuroendocrine tumours.

    Science.gov (United States)

    de Herder, Wouter W

    2007-03-01

    Several circulating or urinary tumour markers can be used for the diagnosis and follow-up of functioning and clinically non-functioning neuroendocrine tumours of the pancreatic islet cells and intestinal tract. Among the specific tumour markers are serotonin and its metabolites--e.g. 5-hydroxyindoleacetic acid (5-HIAA)--in carcinoid tumours and the carcinoid syndrome, insulin and its precursors or breakdown products in insulinoma, and gastrin in gastrinoma. Plasma vasointestinal polypeptide (VIP) determinations have been used in the diagnosis of VIPoma, plasma glucagon for glucagonoma, and serum somatostatin for somatostatinoma. Among the tumour-non-specific markers are: chromogranins, neuron-specific enolase (NSE), alpha-subunits of the glycoprotein hormones, catecholamines, pancreatic polypeptide (PP), ghrelin and adrenomedullin.

  17. 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.

  18. 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.

  19. Phase III randomized study comparing docetaxel plus trastuzumab with vinorelbine plus trastuzumab as first-line therapy of metastatic or locally advanced human epidermal growth factor receptor 2-positive breast cancer: the HERNATA study

    DEFF Research Database (Denmark)

    Andersson, Michael; Lidbrink, Elisabeth; Bjerre, Karsten;

    2011-01-01

    To evaluate docetaxel or vinorelbine, both with trastuzumab, as first-line therapy of human epidermal growth factor receptor 2-positive advanced breast cancer.......To evaluate docetaxel or vinorelbine, both with trastuzumab, as first-line therapy of human epidermal growth factor receptor 2-positive advanced breast cancer....

  20. 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.

  1. 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.

  2. {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

  3. AmotL2 disrupts apical-basal cell polarity and promotes tumour invasion.

    Science.gov (United States)

    Mojallal, Mahdi; Zheng, Yujuan; Hultin, Sara; Audebert, Stéphane; van Harn, Tanja; Johnsson, Per; Lenander, Claes; Fritz, Nicolas; Mieth, Christin; Corcoran, Martin; Lembo, Frédérique; Hallström, Marja; Hartman, Johan; Mazure, Nathalie M; Weide, Thomas; Grandér, Dan; Borg, Jean-Paul; Uhlén, Per; Holmgren, Lars

    2014-08-01

    The establishment and maintenance of apical-basal cell polarity is essential for the functionality of glandular epithelia. Cell polarity is often lost in advanced tumours correlating with acquisition of invasive and malignant properties. Despite extensive knowledge regarding the formation and maintenance of polarity, the mechanisms that deregulate polarity in metastasizing cells remain to be fully characterized. Here we show that AmotL2 expression correlates with loss of tissue architecture in tumours from human breast and colon cancer patients. We further show that hypoxic stress results in activation of c-Fos-dependent expression of AmotL2 leading to loss of polarity. c-Fos/hypoxia-induced p60 AmotL2 interacts with the Crb3 and Par3 polarity complexes retaining them in large vesicles and preventing them from reaching the apical membrane. The resulting loss of polarity potentiates the response to invasive cues in vitro and in vivo in mice. These data provide a molecular mechanism how hypoxic stress deregulates cell polarity during tumour progression.

  4. Targeting CXCR1 on breast cancer stem cells: signaling pathways and clinical application modelling.

    Science.gov (United States)

    Brandolini, Laura; Cristiano, Loredana; Fidoamore, Alessia; De Pizzol, Maria; Di Giacomo, Erica; Florio, Tiziana Marilena; Confalone, Giuseppina; Galante, Angelo; Cinque, Benedetta; Benedetti, Elisabetta; Ruffini, Pier Adelchi; Cifone, Maria Grazia; Giordano, Antonio; Alecci, Marcello; Allegretti, Marcello; Cimini, Annamaria

    2015-12-22

    In breast cancer it has been proposed that the presence of cancer stem cells may drive tumor initiation, progression and recurrences. IL-8, up-regulated in breast cancer, and associated with poor prognosis, increases CSC self-renewal in cell line models. It signals via two cell surface receptors, CXCR1 and CXCR2. Recently, the IL-8/CXCR1 axis was proposed as an attractive pathway for the design of specific therapies against breast cancer stem cells. Reparixin, a powerful CXCR1 inhibitor, was effective in reducing in vivo the tumour-initiating population in several NOD/SCID mice breast cancer models, showing that the selective targeting of CXCR1 and the combination of reparixin and docetaxel resulted in a concomitant reduction of the bulk tumour mass and CSC population. The available data indicate that IL-8, expressed by tumour cells and induced by chemotherapeutic treatment, is a key regulator of the survival and self-renewal of the population of CXCR1-expressing CSC. Consequently, this investigation on the mechanism of action of the reparixin/paclitaxel combination, was based on the observation that reparixin treatment contained the formation of metastases in several experimental models. However, specific data on the formation of breast cancer brain metastases, which carry remarkable morbidity and mortality to a substantial proportion of advanced breast cancer patients, have not been generated. The obtained data indicate a beneficial use of the drug combination reparixin and paclitaxel to counteract brain tumour metastasis due to CSC, probably due to the combined effects of the two drugs, the pro-apoptotic action of paclitaxel and the cytostatic and anti-migratory effects of reparixin.

  5. 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

  6. Bmi-1 promotes invasion and metastasis, and its elevated expression is correlated with an advanced stage of breast cancer

    Directory of Open Access Journals (Sweden)

    Kung Hsiang-Fu

    2011-01-01

    Full Text Available Abstract Background B-lymphoma Moloney murine leukemia virus insertion region-1 (Bmi-1 acts as an oncogene in various tumors, and its overexpression correlates with a poor outcome in several human cancers. Ectopic expression of Bmi-1 can induce epithelial-mesenchymal transition (EMT and enhance the motility and invasiveness of human nasopharyngeal epithelial cells (NPECs, whereas silencing endogenous Bmi-1 expression can reverse EMT and reduce the metastatic potential of nasopharyngeal cancer cells (NPCs. Mouse xenograft studies indicate that coexpression of Bmi-1 and H-Ras in breast cancer cells can induce an aggressive and metastatic phenotype with an unusual occurrence of brain metastasis; although, Bmi-1 overexpression did not result in oncogenic transformation of MCF-10A cells. However, the underlying molecular mechanism of Bmi-1-mediated progression and the metastasis of breast cancer are not fully elucidated at this time. Results Bmi-1 expression is more pronouncedly increased in primary cancer tissues compared to matched adjacent non-cancerous tissues. High Bmi-1 expression is correlated with advanced clinicopathologic classifications (T, N, and M and clinical stages. Furthermore, a high level of Bmi-1 indicates an unfavorable overall survival and serves as a high risk marker for breast cancer. In addition, inverse transcriptional expression levels of Bmi-1 and E-cadherin are detected between the primary cancer tissues and the matched adjacent non-cancerous tissues. Higher Bmi-1 levels are found in the cancer tissue, whereas the paired adjacent non-cancer tissue shows higher E-cadherin levels. Overexpression of Bmi-1 increases the motility and invasive properties of immortalized human mammary epithelial cells, which is concurrent with the increased expression of mesenchymal markers, the decreased expression of epithelial markers, the stabilization of Snail and the dysregulation of the Akt/GSK3β pathway. Consistent with these

  7. 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.

  8. Current data of targeted therapies for the treatment of triple-negative advanced breast cancer: empiricism or evidence-based?

    Science.gov (United States)

    Petrelli, Fausto; Cabiddu, Mary; Ghilardi, Mara; Barni, Sandro

    2009-10-01

    Approximately 10 - 15% of breast carcinomas (BCs) are known to be 'triple-negative (TN) receptor' (i.e., not expressing ER or PR and not exhibiting overexpression and/or gene amplification of HER2-neu). Triple-negative BCs comprise approximately 85% of all basal-type tumours. Classically, basal-like BCs have been characterised by low expression of ER, PR, and HER2 neu and high expression of CK5, CK14, caveolin-1, CAIX, p63, and EGFR (HER1), which reflects the mammary gland basal/myoepithelial cell component. Although there is no standard first-line chemotherapy regimen for metastatic TN BCs, anthracycline- and taxane-containing regimens are acceptable treatments. A large number of agents, including DNA-damaging agents, EGFR inhibitors, antiangiogenic agents and novel taxane formulations are currently being tested in clinical trials for first-line and pretreated patients. Limited experiences with platinum salts, poly(ADP-ribose) polymerase (PARP) inhibitors, cetuximab, bevacizumab and ixabepilone have been published in recent years and will be reported. Novel immunohistochemistry analysis for identification of basal like/TN phenotype are awaited to correctly select this population. The clinical trials investigating new agents have to be designed for a specific (and possibly large) subset of patients with BC. In the future, a gene array platform with greater sensitivity for distinguishing the various BC subtypes, as well as having the power to predict the molecular biology of the disease, will be an indispensible tool for treatment selection. Currently, treatment of TN BC is more empirical than evidence-based. The cornerstone of treatment is chemotherapy, but in the near future, novel target agents will emerge as possible partners.

  9. Gamma-secretase/Notch Signalling Pathway Inhibitor RO4929097 in Treating Patients With Advanced, Metastatic, or Recurrent Triple Negative Invasive Breast Cancer

    Science.gov (United States)

    2017-02-28

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

  10. 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.

  11. Common genomic signaling among initial DNA damage and radiation-induced apoptosis in peripheral blood lymphocytes from locally advanced breast cancer patients

    DEFF Research Database (Denmark)

    Henríquez-Hernández, Luis Alberto; Pinar, Beatriz; Carmona-Vigo, Ruth

    2013-01-01

    suffering from locally advanced breast cancer and treated with high-dose hyperfractionated radiotherapy were recruited. Initial DNA damage was measured by pulsed-field gel electrophoresis and radiation-induced apoptosis was measured by flow cytometry. Gene expression was assessed by DNA microarray. RESULTS...

  12. Bilateral Malignant Brenner Tumour

    Directory of Open Access Journals (Sweden)

    Nasser D Choudhary, S.Manzoor Kadri, Ruby Reshi, S. Besina, Mansoor A. Laharwal, Reyaz tasleem, Qurrat A. Chowdhary

    2002-10-01

    Full Text Available Bilateral malignant Brenner tumour ofovary is extremely rate. A case ofmalignant Brenner tumourinvolving both the ovaries with mctastasis to mesentery in a 48 year femalc is presented. Grosslyo'arian masses were firm with soft areas, encapsulated and having bosselated external surfaces.Cut sections showed yellowish white surface with peripheral cysts (in both tumours. Microscopyrevealed transitional cell carcinoma with squamoid differentiation at places. Metastatic deposits werefound in the mesentery. Endometrium showed cystic glandular hyperplasia.

  13. 三阴性乳腺癌的治疗进展%Treatment Advances of Triple Negative Breast Cancer

    Institute of Scientific and Technical Information of China (English)

    何伟(综述); 于凌飞; 段秀庆(审校)

    2015-01-01

    The estrogen receptor, progesterone receptor and human epidermal growth factor receptor of triple negative breast cancer (TNBC) are negative. Compared to other breast cancer subtypes,TNBC has strong invasiveness,high degree of malignancy and poor prognosis,with high recurrence rate after adjuvant therapy. TNBC is more sensitive to chemotherapy,and cytotoxic drugs are the main drugs. In recent years, with the increasing depth study of tumor molecular biology,molecular targeted therapy for breast cancer has become the focus,and here is to make a review of the treatment advances of TNBC.%三阴性乳腺癌( TNBC)是雌激素受体、孕激素受体以及人表皮生长因子受体均为阴性的乳腺癌。相对于其他乳腺癌亚型,其具有侵袭性强、恶性程度高、患者预后差、辅助治疗后复发转移率高等特点。 TNBC对化疗较为敏感,治疗仍以细胞毒性药物为主。近年来,随着肿瘤分子生物学研究的深入,分子靶向治疗成为近几年乳腺癌研究和关注的焦点。该文就TNBC的治疗进展作一综述。

  14. 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

  15. 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)

    A.M. Mulligan (Anna Marie); F.J. Couch (Fergus); D. Barrowdale (Daniel); S.M. Domchek (Susan); D. Eccles (Diana); H. Nevanlinna (Heli); S.J. Ramus (Susan); M. Robson (Mark); M.E. Sherman (Mark); A.B. Spurdle (Amanda); B. Wapenschmidt (Barbara); A. Lee (Andrew); L. McGuffog (Lesley); S. Healey (Sue); O. Sinilnikova (Olga); R. Janavicius (Ramunas); T.V.O. Hansen (Thomas); F.C. Nielsen (Finn); B. Ejlertsen (Bent); A. Osorio (Ana); I. Muñoz-Repeto (Iván); M. Durán (Mercedes); J. Godino (Javier); M. Pertesi (Maroulio); J. Benítez (Javier); P. Peterlongo (Paolo); S. Manoukian (Siranoush); B. Peissel (Bernard); D. Zaffaroni (D.); E. Cattaneo (Elisa); B. Bonnani (Bernardo); A. Viel (Alessandra); B. Pasini (Barbara); L. Papi (Laura); L. Ottini (Laura); A. Savarese (Antonella); L. Bernard (Loris); P. Radice (Paolo); U. Hamann (Ute); M. Verheus (Martijn); E.J. Meijers-Heijboer (Hanne); J.T. Wijnen (Juul); E.B. Gómez García (Encarna); M.R. Nelen (Marcel); C.M. Kets; C.M. Seynaeve (Caroline); M.M.A. Tilanus-Linthorst (Madeleine); R.B. van der Luijt (Rob); T.V. Os (Theo); M.A. Rookus (Matti); D. Frost (Debra); J.L. Jones (J Louise); D.G. Evans (Gareth); F. Lalloo (Fiona); R. Eeles (Rosalind); L. Izatt (Louise); J.W. Adlard (Julian); R. Davidson (Rosemarie); J. Cook (Jackie); A. Donaldson (Alan); H. Dorkins (Huw); H. Gregory (Helen); J. Eason (Jacqueline); C. Houghton (Catherine); J. Barwell (Julian); L. Side (Lucy); E. McCann (Emma); A. Murray (Alexandra); S. Peock (Susan); A.K. Godwin (Andrew); R.K. Schmutzler (Rita); K. Rhiem (Kerstin); C. Engel (Christoph); A. Meindl (Alfons); I. Ruehl (Ina); N. Arnold (Norbert); D. Niederacher (Dieter); C. Sutter (Christian); H. Deissler (Helmut); D. Gadzicki (Dorothea); K. Kast (Karin); S. Preisler-Adams (Sabine); R. Varon-Mateeva (Raymonda); I. Schoenbuchner (Ines); B. Fiebig (Britta); W. Heinritz (Wolfram); D. Schäfer; H. Gevensleben (Heidrun); V. Caux-Moncoutier (Virginie); M. Fassy-Colcombet (Marion); F. Cornelis (Franco̧is); S. Mazoyer (Sylvie); M. Léone (Mélanie); N. Boutry-Kryza (N.); A. Hardouin (Agnès); P. Berthet (Pascaline); D.W. Muller (Danièle); J.P. Fricker (Jean Pierre); I. Mortemousque (Isabelle); P. Pujol (Pascal); I. Coupier (Isabelle); M. Lebrun (Marine); C. Kientz (Caroline); M. Longy (Michel); N. Sevenet (Nicolas); D. Stoppa-Lyonnet (Dominique); C. Isaacs (Claudine); T. Caldes (Trinidad); M. de La Hoya (Miguel); T. Heikinen (Tuomas); K. Aittomäki (Kristiina); I. Blanco (Ignacio); C. Lazaro (Conxi); R.B. Barkardottir (Rosa); P. Soucy (Penny); M. Dumont (Martine); J. Simard (Jacques); M. Montagna (Marco); S. Tognazzo (Silvia); E. D'Andrea (Emma); S.B. Fox (Stephen); M. Yan (Max); R. Rebbeck (Timothy); O.I. Olopade (Olofunmilayo); J.N. Weitzel (Jeffrey); H. Lynch (Henry); P.A. Ganz (Patricia); G. Tomlinson (Gail); X. Wang (Xing); Z. Fredericksen (Zachary); V.S. Pankratz (Shane); N.M. Lindor (Noralane); C. Szabo (Csilla); K. Offit (Kenneth); R. Sakr (Rita); M.M. Gaudet (Mia); K.P. Bhatia (Kailash); N. Kauff (Noah); C.F. Singer (Christian); M.-K. Tea; D. Gschwantler-Kaulich (Daphne); A. Fink-Retter (Anneliese); P.L. Mai (Phuong); M.H. Greene (Mark); E.N. Imyanitov (Evgeny); F.P. O'Malley (Frances); H. Ozcelik (Hilmi); G. Glendon (Gord); A.E. Toland (Amanda); A-M. Gerdes (Anne-Marie); M. Thomassen (Mads); T.A. Kruse (Torben); U.B. Jensen; A.-B. Skytte (Anne-Bine); M.A. Caligo (Maria); M. Soller (Maria); K. Henriksson (Karin); A. von Wachenfeldt (Anna); B. Arver (Brita Wasteson); M. Stenmark-Askmalm (M.); P. Karlsson (Per); Y.C. Ding (Yuan); S.L. Neuhausen (Susan); M.S. Beattie (Mary); P.D.P. Pharoah (Paul); K.B. Moysich (Kirsten); K.L. Nathanson (Katherine); B. Karlan; J. Gross (Jenny); E.M. John (Esther); M.B. Daly (Mary); S.S. Buys (Saundra); M.C. Southey (Melissa); J.L. Hopper (John); M.-B. Terry (Mary-Beth); W. Chung (Wendy); A. Miron (Alexander); D. Goldgar (David); G. Chenevix-Trench (Georgia); D.F. Easton (Douglas); I.L. Andrulis (Irene); A.C. Antoniou (Antonis)

    2011-01-01

    textabstractIntroduction: 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

  16. 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

  17. Expression of Erk5 in early stage breast cancer and association with disease free survival identifies this kinase as a potential therapeutic target.

    Directory of Open Access Journals (Sweden)

    Juan Carlos Montero

    Full Text Available BACKGROUND: Breast cancer is the most common neoplasia in women. Even though advances in its treatment have improved disease outcome, some patients relapse. Therefore, attempts to better define the molecular determinants that drive breast cancer cell proliferation may help in defining potential therapeutic targets. Mitogen-activated protein kinases (MAPK play important roles in tumorigenesis. One of them, Erk5, has been linked to the proliferation of breast cancer cells in vitro. Here we have investigated the expression and prognostic value of Erk5 in human breast cancer. METHODOLOGY/PRINCIPAL FINDINGS: Animal and cellular models were used to study Erk5 expression and function in breast cancer. In 84 human breast tumours the expression of Erk5 was analyzed by immunohistochemistry. Active Erk5 (pErk5 was studied by Western blotting. Correlation of Erk5 with clinicopathological parameters and with disease-free survival in early stage breast cancer patients was analyzed. Expression of Erk5 was detected in most patients, and overexpression was found in 20%. Active Erk5 was present in a substantial number of samples, as well as in tumours from an animal breast cancer model. Overexpression of Erk5 was associated with a decrease in disease-free survival time, which was independent of other clinicopathological parameters of prognosis. Transient transfection of a short hairpin RNA (shRNA targeting Erk5, and a stable cell line expressing a dominant negative form of Erk5 (Erk5(AEF, were used to investigate the influence of Erk5 on drugs used in the clinic to treat breast tumours. We found that inhibition of Erk5 decreased cancer cell proliferation and also sensitized these cells to the action of anti-HER2 therapies. CONCLUSIONS/SIGNIFICANCE: Overexpression of Erk5 is an independent predictor of disease-free survival in breast cancer, and may represent a future therapeutic target.

  18. 乳腺疾病的MRI研究进展%Advances in breast diseases MRI

    Institute of Scientific and Technical Information of China (English)

    黄娟; 田军章; 江桂华

    2011-01-01

    MRI has excellent soft tissue resolution,and this technology is more and more widely used in breast disease diagnosis in recent years.Blood supply and perfusion through the microvascular network of tumor can be imaged noninvasively by dynamic contrast-enhanced MRI and perfusion-weighted imaging.Diffusion-weighted imaging and magnetic resonance spectroscopy can provide molecular information of breast lesions.Magnetic resonance ductography provides a new technology for detecting intraductal breast lesions.With MRI technology maturing and the rapid development of software and hardware,MRI shows its unique advantages in breast lesions characterization.%MRI具有极佳的软组织分辨率,近年来,该技术越来越广泛的应用于乳腺疾病的诊断.乳腺动态增强成像和灌注加权成像可从不同角度反映乳腺组织及病灶的血供灌注情况,弥散加权成像和磁共振波谱分析则从分子水平提供乳腺病变组织信息,磁共振乳腺导管成像为导管内病变提供了新的影像诊断方法.随着MRI技术的成熟、软硬件的迅速发展,MRI在乳腺疾病的检出和诊断方面显示出其独到的优势.

  19. Are work-related stressors associated with diagnosis of more advanced stages of incident breast cancers?

    DEFF Research Database (Denmark)

    Nielsen, Naja Rod; Stahlberg, Claudia; Strandberg-Larsen, Katrine;

    2008-01-01

    OBJECTIVE: To assess the relation between work-related stressors and breast cancer incidence and prognostic characteristics (estrogen receptor status, grade, lymph node status, size, stage) at the time of diagnosis. METHODS: The 18,932 women included in the Danish Nurse Cohort reported work......-related stressors in 1993 and again in 1999 and were followed until the end of 2003 in national registries. Prognostic characteristics were obtained from a clinical database and fewer than 0.1% were lost to follow up. RESULTS: During follow-up, 455 women were diagnosed with breast cancer. Neither women with high...... work pressure (HR = 1.17; 95% CI: 0.79, 1.73) nor women with self-reported low influence on work organization (0.98; 0.69, 1.39) or long working hours (0.93; 0.54, 1.58) were at higher risk of breast cancer than women with no such stressors. Women with high work tempo had a slightly higher risk...

  20. Energy balance in patients with advanced NSCLC, metastatic melanoma and metastatic breast cancer receiving chemotherapy--a longitudinal study.

    Science.gov (United States)

    Harvie, M N; Howell, A; Thatcher, N; Baildam, A; Campbell, I

    2005-02-28

    Chemotherapy exerts a variable effect on nutritional status. It is not known whether loss of body fat or fat-free mass (FFM) during chemotherapy relates to diminished dietary intake, failure to meet elevated energy requirements, or to the presence of an acute-phase response. We sought to determine prospective measurements of body mass and composition, resting energy expenditure, energy and protein intake, and C-reactive protein over a course of chemotherapy in 82 patients with advanced cancer. There was a large dropout from the study. Prospective measurements were obtained in 19 patients with non-small-cell lung cancer (NSCLC), 12 with metastatic melanoma and 10 with metastatic breast cancer. There were significant increases in energy intake among patients with metastatic breast cancer, 873 (266-1480) kJ (mean 95% CI; Pcancer patients gained percentage body fat over the course of treatment, 2.1 (0.8-3.5%). Gain or loss of body fat correlated to mean energy intake throughout chemotherapy in patients with NSCLC (Rs=0.751; Pcancer (Rs=0.617; Pcancer and NSCLC, but did not prevent loss of FFM in these groups.

  1. A phase I, dose-escalation study of TB-403, a monoclonal antibody directed against PlGF, in patients with advanced solid tumours

    DEFF Research Database (Denmark)

    Lassen, U; Nielsen, D L; Sørensen, M;

    2012-01-01

    BACKGROUND: TB-403 (RO 5323441), a humanised monoclonal antibody, is a novel antiangiogenesis agent directed against placental growth factor. The safety, pharmacokinetics (PK), and antitumour activity of TB-403 were assessed in a phase I, dose-escalation study in patients with advanced solid...

  2. Tamoxifen Citrate or Z-Endoxifen Hydrochloride in Treating Patients With Locally Advanced or Metastatic, Estrogen Receptor-Positive, HER2-Negative Breast Cancer

    Science.gov (United States)

    2017-01-23

    Estrogen Receptor Positive; HER2/Neu Negative; Recurrent Breast Carcinoma; Stage III Breast Cancer; Stage IIIA Breast Cancer; Stage IIIB Breast Cancer; Stage IIIC Breast Cancer; Stage IV Breast Cancer

  3. Tumour biology: Herceptin acts as an anti-angiogenic cocktail

    Science.gov (United States)

    Izumi, Yotaro; Xu, Lei; di Tomaso, Emmanuelle; Fukumura, Dai; Jain, Rakesh K.

    2002-03-01

    Malignant tumours secrete factors that enable them to commandeer their own blood supply (angiogenesis), and blocking the action of these factors can inhibit tumour growth. But because tumours may become resistant to treatments that target individual angiogenic factors by switching over to other angiogenic molecules, a cocktail of multiple anti-angiogenic agents should be more effective. Here we show that herceptin, a monoclonal antibody against the cell-surface receptor HER2 (for human epidermal growth factor receptor-2; ref. 4), induces normalization and regression of the vasculature in an experimental human breast tumour that overexpresses HER2 in mice, and that it works by modulating the effects of different pro- and anti-angiogenic factors. As a single agent that acts against multiple targets, herceptin, or drugs like it, may offer a simple alternative to combination anti-angiogenic treatments.

  4. A proof-of-principle study of epigenetic therapy added to neoadjuvant doxorubicin cyclophosphamide for locally advanced breast cancer.

    Directory of Open Access Journals (Sweden)

    Claudia Arce

    Full Text Available Aberrant DNA methylation and histone deacetylation participate in cancer development and progression; hence, their reversal by inhibitors of DNA methylation and histone deacetylases (HDACs is at present undergoing clinical testing in cancer therapy. As epigenetic alterations are common to breast cancer, in this proof-of-concept study demethylating hydralazine, plus the HDAC inhibitor magnesium valproate, were added to neoadjuvant doxorubicin and cyclophosphamide in locally advanced breast cancer to assess their safety and biological efficacy.This was a single-arm interventional trial on breast cancer patients (ClinicalTrials.gov Identifier: NCT00395655. After signing informed consent, patients were typed for acetylator phenotype and then treated with hydralazine at 182 mg for rapid-, or 83 mg for slow-acetylators, and magnesium valproate at 30 mg/kg, starting from day -7 until chemotherapy ended, the latter consisting of four cycles of doxorubicin 60 mg/m2 and cyclophosphamide 600 mg/m2 every 21 days. Core-needle biopsies were taken from primary breast tumors at diagnosis and at day 8 of treatment with hydralazine and valproate.16 patients were included and received treatment as planned. All were evaluated for clinical response and toxicity and 15 for pathological response. Treatment was well-tolerated. The most common toxicity was drowsiness grades 1-2. Five (31% patients had clinical CR and eight (50% PR for an ORR of 81%. No patient progressed. One of 15 operated patients (6.6% had pathological CR and 70% had residual disease <3 cm. There was a statistically significant decrease in global 5mC content and HDAC activity. Hydralazine and magnesium valproate up- and down-regulated at least 3-fold, 1,091 and 89 genes, respectively.Hydralazine and magnesium valproate produce DNA demethylation, HDAC inhibition, and gene reactivation in primary tumors. Doxorubicin and cyclophosphamide treatment is safe, well-tolerated, and appears to increase the

  5. HORMONE THERAPY IN ADVANCED ER+/HER2- NEGATIVE BREAST CANCER WITH PI3K INHIBITORS: A REVIEW OF THE LITERATURE

    Directory of Open Access Journals (Sweden)

    Ivan Inkov

    2016-08-01

    Full Text Available Breast cancer is a heterogenous disease, showing as several different clinical and histologic types. Most of breast cancers express hormone receptors for estrogen and progesterone, which are considered as estrogen receptor-positive and progesterone-receptor-positive, respectively. Endocrine therapy was the first class of target-directed therapy approved for treating breast cancer and is still very important for the treatment of HR+ breast cancer because of its effectiveness and good toxicity profile. It targets receptor-mediated signaling pathways implicated in cell survival and proliferation, such as those mediated by hormone receptors. Although these approaches have improved the management of advanced breast cancer, many patients either fail to respond to initial therapy (primary or de novo resistance or eventually become resistant to treatment (secondary or acquired resistance. To expand the use of existing endocrine treatments and their efficiency, new methods are needed. Such new approaches would boost the benefit of existing endocrine therapy by extending time to disease progression, avoiding or overcoming resistance to endocrine treatment, and delaying the use of chemotherapy. This article will review the central role of the PI3K inhibitors in driving ER+/HER2- breast tumors. Also, schemes to combine pathway inhibitors with endocrine therapy for better patient outcome, and approaches to identify patient populations that would benefit most from inhibition of the PI3K/AKT/mTOR pathway will be assessed.

  6. Triple-negative breast cancer: epidemiological considerations and recommendations.

    Science.gov (United States)

    Boyle, P

    2012-08-01

    Breast cancer is a major problem for global public health. Breast Cancer is the most common incident form of cancer in women around the world. The incidence is increasing while mortality is declining in many high-income countries. The last decade has seen a revolution in the understanding of breast cancer, with new classifications proposed that have significant prognostic value and provide guides to treatment options. Breast cancers that demonstrate the absence of oestrogen receptor and progesterone receptor and no overexpression of human epidermal growth factor receptor 2 (HER2) are referred to as triple-negative breast cancer (TNBC). There is now evidence emerging from epidemiological studies regarding important characteristics of this group of tumours that carry a relatively poorer prognosis than the major breast cancer sub-types. From this review of available data and information, there are some consistent findings that emerge. Women with TNBC experience the peak risk of recurrence within 3 years of diagnosis, and the mortality rates appear to be increased for 5 years after diagnosis. TNBC represents 10%-20% of invasive breast cancers and has been associated with African-American race, deprivation status, younger age at diagnosis, more advanced disease stage, higher grade, high mitotic indices, family history of breast cancer and BRCA1 mutations. TNBC is regularly reported to be three times more common in women of African descent and in pre-menopausal women, and carries a poorer prognosis than other forms of breast cancer. Although prospects for prevention of non-hormone-dependent breast cancer are currently poor, it is still important to understand the aetiology of such tumours. There remains a great deal of work to be done to arrive at a comprehensive picture of the aetiology of breast cancer. Key recommendations are that there is a clear and urgent need to have more epidemiological studies of the breast cancer sub-types to integrate aetiological and

  7. Current advances in biomarkers for targeted therapy in triple-negative breast cancer

    Directory of Open Access Journals (Sweden)

    Fleisher B

    2016-10-01

    Full Text Available Brett Fleisher,1 Charlotte Clarke,2 Sihem Ait-Oudhia1 1Department of Pharmaceutics, Center for Pharmacometrics and Systems Pharmacology, College of Pharmacy, University of Florida, Orlando, FL, 2Department of Translational Research, UT MD Anderson Cancer Center, Houston, TX, USA Abstract: Triple-negative breast cancer (TNBC is a complex heterogeneous disease characterized by the absence of three hallmark receptors: human epidermal growth factor receptor 2, estrogen receptor, and progesterone receptor. Compared to other breast cancer subtypes, TNBC is more aggressive, has a higher prevalence in African-Americans, and more frequently affects younger patients. Currently, TNBC lacks clinically accepted targets for tailored therapy, warranting the need for candidate biomarkers. BiomarkerBase, an online platform used to find biomarkers reported in clinical trials, was utilized to screen all potential biomarkers for TNBC and select only the ones registered in completed TNBC trials through clinicaltrials.gov. The selected candidate biomarkers were classified as surrogate, prognostic, predictive, or pharmacodynamic (PD and organized by location in the blood, on the cell surface, in the cytoplasm, or in the nucleus. Blood biomarkers include vascular endothelial growth factor/vascular endothelial growth factor receptor and interleukin-8 (IL-­8; cell surface biomarkers include EGFR, insulin-like growth factor binding protein, c-Kit, c-Met, and PD-L1; cytoplasm biomarkers include PIK3CA, pAKT/S6/p4E-BP1, PTEN, ALDH1, and the PIK3CA/AKT/mTOR-related metabolites; and nucleus biomarkers include BRCA1, the glucocorticoid receptor, TP53, and Ki67. Candidate biomarkers were further organized into a “cellular protein network” that demonstrates potential connectivity. This review provides an inventory and reference point for promising biomarkers for breakthrough targeted therapies in TNBC. Keywords: anti-cancer directed pharmacotherapy, difficult

  8. Glycogen-rich clear cell carcinoma of the breast

    DEFF Research Database (Denmark)

    Sørensen, Flemming Brandt; Paulsen, S M

    1987-01-01

    The light microscopic, immunohistochemical and ultrastructural features of a clear cell carcinoma of the breast have been studied. Both intraductal and invasive components were found. Histochemistry showed large amounts of intracytoplasmic glycogen and sparse neutral mucin in the tumour. The tumour...... was classified as a mucin-containing variant of glycogen-rich, clear cell carcinoma of the breast....

  9. 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.

  10. 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

  11. Breast Cancer 2012 - New Aspects.

    Science.gov (United States)

    Kolberg, H-C; Lüftner, D; Lux, M P; Maass, N; Schütz, F; Fasching, P A; Fehm, T; Janni, W; Kümmel, S

    2012-07-01

    Treatment options as well as the characteristics for therapeutic decisions in patients with primary and advanced breast cancer are increasing in number and variety. New targeted therapies in combination with established chemotherapy schemes are broadening the spectrum, however potentially promising combinations do not always achieve a better result. New data from the field of pharmacogenomics point to prognostic and predictive factors that take not only the properties of the tumour but also inherited genetic properties of the patient into consideration. Current therapeutic decision-making is thus based on a combination of classical clinical and modern molecular biomarkers. Also health-economic aspects are more frequently being taken into consideration so that health-economic considerations may also play a part. This review is based on information from the recent annual congresses. The latest of these are the 34th San Antonio Breast Cancer Symposium 2011 and the ASCO Annual Meeting 2012. Among their highlights are the clinically significant results from the CLEOPATRA, BOLERO-2, EMILIA and SWOG S0226 trials on the therapy for metastatic breast cancer as well as further state-of-the-art data on the adjuvant use of bisphosphonates within the framework of the ABCSG-12, ZO-FAST, NSABP-B34 and GAIN trials.

  12. Orbital tumours and tumour-like lesions: exploring the armamentarium of multiparametric imaging.

    Science.gov (United States)

    Purohit, Bela S; Vargas, Maria Isabel; Ailianou, Angeliki; Merlini, Laura; Poletti, Pierre-Alexandre; Platon, Alexandra; Delattre, Bénédicte M; Rager, Olivier; Burkhardt, Karim; Becker, Minerva

    2016-02-01

    Although the orbit is a small anatomical space, the wide range of structures present within it are often the site of origin of various tumours and tumour-like conditions, both in adults and children. Cross-sectional imaging is mandatory for the detection, characterization, and mapping of these lesions. This review focuses on multiparametric imaging of orbital tumours. Each tumour is reviewed in relation to its clinical presentation, compartmental location, imaging characteristics, and its histological features. We herein describe orbital tumours as lesions of the globe (retinoblastoma, uveal melanoma), optic nerve sheath complex (meningioma, optic nerve glioma), conal-intraconal compartment (hemangioma), extraconal compartment (dermoid/epidermoid, lacrimal gland tumours, lymphoma, rhabdomysarcoma), and bone and sinus compartment (fibrous dysplasia). Lesions without any typical compartmental localization and those with multi-compartment involvement (veno-lymphatic malformation, plexiform neurofibroma, idiopathic orbital pseudotumour, IgG4 related disease, metastases) are also reviewed. We discuss the role of advanced imaging techniques, such as MR diffusion-weighted imaging (DWI), diffusion tensor imaging, fluoro-2-deoxy-D-glucose positron emission tomography CT (FDG-PET CT), and positron emission tomography MRI (MRI PET) as problem-solving tools in the evaluation of those orbital masses that present with non-specific morphologic imaging findings. Main messages/Teaching points • A compartment-based approach is essential for the diagnosis of orbital tumours. • CT and MRI play a key role in the work-up of orbital tumours. • DWI, PET CT, and MRI PET are complementary tools to solve diagnostic dilemmas. • Awareness of salient imaging pearls and diagnostic pitfalls avoids interpretation errors.

  13. Aberrant expression of Arpin in human breast cancer and its clinical significance.

    Science.gov (United States)

    Liu, Xiangping; Zhao, Bin; Wang, Haibo; Wang, Yu; Niu, Mengdi; Sun, Ming; Zhao, Yang; Yao, Ruyong; Qu, Zhiqiang

    2016-03-01

    Arpin (Arp2/3 complex inhibitor), a novel protein found in 2013, plays a pivotal role in cell motility and migration. However, the precise role of Arpin in cancer is unclear. This study investigated the expression of Arpin in breast cancer and evaluated its correlation with the characteristics of clinical pathology and prognosis of breast cancer patients. Immunohistochemistry (IHC) for Arpin protein was performed on formalin-fixed, paraffin-embedded 176 breast cancer tissues and 43 normal breast tissues while qRT-PCR for Arpin mRNA with 104 paired tumour and paratumoural tissues from breast cancer patients respectively. The association of Arpin expression with clinical pathological features and survival was assessed in a retrospective cohort analysis of patients. The results showed that the expression of Arpin protein in cancer tissues was lower compared to that in normal breast and the expression of Arpin mRNA was also lower in cancer tissues than that in the matched paratumoural tissues. Among the 176 breast cancer patients, the lower expression of Arpin was significantly associated with advanced tumour, nodes and metastasis system stage, and the reduced Arpin expression was strongly associated with axillary lymph node metastasis using univariate and multivariate logistic regression analysis [odds ratio: 3.242; 95% confidence interval (CI): 1.526, 6.888; P breast cancer tissues with qRT-PCR and IHC, our results suggest that Arpin downregulation may contribute to the initiation and development of breast cancer metastasis. Therefore, as a potential predictive marker, Arpin deserves future studies.

  14. 乳腺癌基因治疗的研究进展%Advances in Gene Therapy of Breast Cancer

    Institute of Scientific and Technical Information of China (English)

    杜力成; 王栋

    2012-01-01

    我国乳腺癌发病率呈逐年上升趋势,已居女性恶性肿瘤的首位.尽管以手术治疗为主,多种治疗为辅的临床综合治疗模式明显提高了乳腺癌患者的生存率,但晚期和复发性乳腺癌的治疗仍是困扰临床医师的难题.随着乳腺癌相关基因研究的进展及靶向药物的临床应用,乳腺癌的基因治疗显示出了良好的应用前景,基因靶向治疗有望成为治疗晚期及复发性乳腺癌的有效手段.%Breast cancer incidence is increasing year by year in China, which has become the leading cause of death among female malignant tumors. The survival rate has improved with the progress of comprehensive clinical treatments of operation therapy supplemented by a variety of other treatments. However, the advanced-stage and recurrence are still hard problems for clinicians. With the rapid progress of research in cancer related genes and the application of targeted medicine, gene therapy shows promise, especially in advanced and recurrent cases.

  15. 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

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

    Directory of Open Access Journals (Sweden)

    Cardoso Sérgio V

    2007-11-01

    Full Text Available Abstract Background 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. Methods 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. Results 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. Conclusion 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.

  17. Parallel evolution of tumour subclones mimics diversity between tumours.

    Science.gov (United States)

    Martinez, Pierre; Birkbak, Nicolai Juul; Gerlinger, Marco; McGranahan, Nicholas; Burrell, Rebecca A; Rowan, Andrew J; Joshi, Tejal; Fisher, Rosalie; Larkin, James; Szallasi, Zoltan; Swanton, Charles

    2013-08-01

    Intratumour heterogeneity (ITH) may foster tumour adaptation and compromise the efficacy of personalized medicine approaches. The scale of heterogeneity within a tumour (intratumour heterogeneity) relative to genetic differences between tumours (intertumour heterogeneity) is unknown. To address this, we obtained 48 biopsies from eight stage III and IV clear cell renal cell carcinomas (ccRCCs) and used DNA copy-number analyses to compare biopsies from the same tumour with 440 single tumour biopsies from the Cancer Genome Atlas (TCGA). Unsupervised hierarchical clustering of TCGA and multi-region ccRCC samples revealed segregation of samples from the same tumour into unrelated clusters; 25% of multi-region samples appeared more similar to unrelated samples than to any other sample originating from the same tumour. We found that the majority of recurrent DNA copy number driver aberrations in single biopsies were not present ubiquitously in late-stage ccRCCs and were likely to represent subclonal events acquired during tumour progression. Such heterogeneous subclonal genetic alterations within individual tumours may impair the identification of robust ccRCC molecular subtypes classified by distinct copy number alterations and clinical outcomes. The co-existence of distinct subclonal copy number events in different regions of individual tumours reflects the diversification of individual ccRCCs through multiple evolutionary routes and may contribute to tumour sampling bias and impact upon tumour progression and clinical outcome.

  18. High-dose ifosfamide and mesna in advanced breast cancer. A phase II study.

    Science.gov (United States)

    Sanchiz, F; Milla, A

    1990-01-01

    Thirty-two patients with metastatic breast cancer had previously been treated with chemotherapy (including anthracyclines). They were included in a trial to receive 6 g/m3 ifosfamide, mixed with 6 g/m2 mesna in 1000 ml saline infusion, infused over 4 h. Therapy was repeated every 21 days; the dose was reduced by 50%. Twenty-eight patients could be evaluated. An average of 4.2 cycles (range 2-8) was applied. One patient (4%) showed complete remission. Ten patients (36%) had a partial response. Ten patients (36%) experienced SD and the remaining patients (25%) PD. We conclude that high-dose ifosfamide shows activity in this group of pretreated patients and merits further investigation.

  19. Radiation binary targeted therapy for HER-2 positive breast cancers: assumptions, theoretical assessment and future directions

    Energy Technology Data Exchange (ETDEWEB)

    Mundy, Daniel W [School of Nuclear Engineering, Purdue University, 400 Central Drive, West Lafayette, IN 47909 (United States); Harb, Wael [Horizon Oncology, The Care Group, Unity Medical Center, Lafayette, IN 47901 (United States); Jevremovic, Tatjana [School of Nuclear Engineering, Purdue University, 400 Central Drive, West Lafayette, IN 47909 (United States)

    2006-03-21

    A novel radiation targeted therapy is investigated for HER-2 positive breast cancers. The proposed concept combines two known approaches, but never used together for the treatment of advanced, relapsed or metastasized HER-2 positive breast cancers. The proposed radiation binary targeted concept is based on the anti HER-2 monoclonal antibodies (MABs) that would be used as vehicles to transport the nontoxic agent to cancer cells. The anti HER-2 MABs have been successful in targeting HER-2 positive breast cancers with high affinity. The proposed concept would utilize a neutral nontoxic boron-10 predicting that anti HER-2 MABs would assure its selective delivery to cancer cells. MABs against HER-2 have been a widely researched strategy in the clinical setting. The most promising antibody is Trastuzumab (Herceptin (registered) ). Targeting HER-2 with the MAB Trastuzumab has been proven to be a successful strategy in inducing tumour regression and improving patient survival. Unfortunately, these tumours become resistant and afflicted women succumb to breast cancer. In the proposed concept, when the tumour region is loaded with boron-10 it is irradiated with neutrons (treatment used for head and neck cancers, melanoma and glioblastoma for over 40 years in Japan and Europe). The irradiation process takes less than an hour producing minimal side effects. This paper summarizes our recent theoretical assessments of radiation binary targeted therapy for HER-2 positive breast cancers on: the effective drug delivery mechanism, the numerical model to evaluate the targeted radiation delivery and the survey study to find the neutron facility in the world that might be capable of producing the radiation effect as needed. A novel method of drug delivery utilizing Trastuzumab is described, followed by the description of a computational Monte Carlo based breast model used to determine radiation dose distributions. The total flux and neutron energy spectra of five currently available

  20. Detection of breast cancer using advanced techniques of data mining with neural networks; Deteccion de cancer de mama usando tecnicas avanzadas de mineria de datos con redes neuronales

    Energy Technology Data Exchange (ETDEWEB)

    Ortiz M, J. A.; Celaya P, J. M.; Martinez B, M. R.; Solis S, L. O.; Castaneda M, R.; Garza V, I.; Martinez F, M.; Lopez H, Y.; Ortiz R, J. M. [Universidad Autonoma de Zacatecas, Av. Ramon Lopez Velarde 801, Col. Centro, 98000 Zacatecas, Zac. (Mexico)

    2016-10-15

    The breast cancer is one of the biggest health problems worldwide, is the most diagnosed cancer in women and prevention seems impossible since its cause is unknown, due to this; the early detection has a key role in the patient prognosis. In developing countries such as Mexico, where access to specialized health services is minimal, the regular clinical review is infrequent and there are not enough radiologists; the most common form of detection of breast cancer is through self-exploration, but this is only detected in later stages, when is already palpable. For these reasons, the objective of the present work is the creation of a system of computer assisted diagnosis (CAD x) using information analysis techniques such as data mining and advanced techniques of artificial intelligence, seeking to offer a previous medical diagnosis or a second opinion, as if it was a second radiologist in order to reduce the rate of mortality from breast cancer. In this paper, advances in the design of computational algorithms using computer vision techniques for the extraction of features derived from mammograms are presented. Using data mining techniques of data mining is possible to identify patients with a high risk of breast cancer. With the information obtained from the mammography analysis, the objective in the next stage will be to establish a methodology for the generation of imaging bio-markers to establish a breast cancer risk index for Mexican patients. In this first stage we present results of the classification of patients with high and low risk of suffering from breast cancer using neural networks. (Author)

  1. 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.

  2. Bacterial targeted tumour therapy-dawn of a new era.

    Science.gov (United States)

    Wei, Ming Q; Mengesha, Asferd; Good, David; Anné, Jozef

    2008-01-18

    Original observation of patients' spontaneous recovery from advanced tumours after an infection or a "fever" inspired extensive research. As a result, Coley's toxin for the therapy of sarcomas and live Bacillus Calmette-Guerin (BCG) for bladder cancer were born. In addition, three genera of anaerobic bacteria have been shown to specifically and preferentially target solid tumours and cause significant tumour lyses. Initial research had focused on determining the best tumour colonizing bacteria, and assessing the therapeutic efficacy of different strategies either as a single or combination treatment modalities. However, although clinical trials were carried out as early as the 1960s, lack of complete tumour lyses with injection of Clostridial spores had limited their further use. Recent progress in the field has highlighted the rapid development of new tools for genetic manipulation of Clostridia which have otherwise been a hurdle for a long time, such as plasmid transformation using electroporation that bore the problems of inefficiency, instability and plasmid loss. A new Clostridium strain, C. novyi-NT made apathogenic by genetic modification, is under clinical trials. New genetic engineering tools, such as the group II intron has shown promise for genetic manipulation of bacteria and forecast the dawn of a new era for a tumour-targeted bacterial vector system for gene therapy of solid tumours. In this review we will discuss the potential of genetically manipulated bacteria that will usher in the new era of bacterial therapy for solid tumours, and highlight strategies and tools used to improve the bacterial oncolytic capability.

  3. TFF3 is a normal breast epithelial protein and is associated with differentiated phenotype in early breast cancer but predisposes to invasion and metastasis in advanced disease.

    Science.gov (United States)

    Ahmed, Ahmed R H; Griffiths, Andrew B; Tilby, Michael T; Westley, Bruce R; May, Felicity E B

    2012-03-01

    The trefoil protein TFF3 stimulates invasion and angiogenesis in vitro. To determine whether it has a role in breast tumor metastasis and angiogenesis, its levels were measured by immunohistochemistry in breast tissue with a specific monoclonal antibody raised against human TFF3. TFF3 is expressed in normal breast lobules and ducts, at higher levels in areas of fibrocystic change and papillomas, in all benign breast disease lesions, and in 89% of in situ and in 83% of invasive carcinomas. In well-differentiated tumor cells, TFF3 is concentrated at the luminal edge, whereas in poorly differentiated cells polarity is inverted and expression is directed toward the stroma. Expression was high in well-differentiated tumors and was associated significantly with low histological grade and with estrogen and progesterone receptor expression, accordant with induction of TFF3 mRNA by estrogen in breast cancer cells. Paradoxically, TFF3 expression was associated with muscle, neural, and lymphovascular invasion and the presence and number of involved lymph nodes, and it was an independent predictive marker of lymphovascular invasion and lymph node involvement. Consistent with an angiogenic function, TFF3 expression correlated strongly with microvessel density evaluated with CD31 and CD34. In conclusion, TFF3 is expressed in both the normal and diseased breast. Although associated with features of good prognosis, its profile of expression in invasive cancer is consistent with a role in breast tumor progression and tumor cell dissemination.

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

    LENUS (Irish Health Repository)

    Wu, Q D

    2012-02-03

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

  5. 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.

  6. Treatment challenges for community oncologists treating postmenopausal women with endocrine-resistant, hormone receptor-positive, human epidermal growth factor receptor 2-negative advanced breast cancer

    Directory of Open Access Journals (Sweden)

    Gradishar WJ

    2016-07-01

    Full Text Available William J Gradishar Division of Hematology/Oncology, Department of Medicine, Northwestern University Feinberg School of Medicine, Chicago, IL, USA Abstract: Community-based oncologists are faced with challenges and opportunities when delivering quality patient care, including high patient volumes and diminished resources; however, there may be the potential to deliver increased patient education and subsequently improve outcomes. This review discusses the treatment of postmenopausal women with endocrine-resistant, hormone receptor-positive, human epidermal growth factor receptor 2-negative advanced breast cancer in order to illustrate considerations in the provision of pertinent quality education in the treatment of these patients and the management of therapy-related adverse events. An overview of endocrine-resistant breast cancer and subsequent treatment challenges is also provided. Approved treatment options for endocrine-resistant breast cancer include hormonal therapies and mammalian target of rapamycin inhibitors. Compounds under clinical investigation are also discussed. Keywords: community oncologists, hormone receptor-positive advanced breast cancer, endocrine resistance

  7. Current role of bone scan with phosphonates in the follow-up of breast cancer

    Energy Technology Data Exchange (ETDEWEB)

    Maffioli, Lorenzo; Florimonte, Luigia; Pagani, Luca; Butti, Ivana [Division of Nuclear Medicine, Ospedale ' ' A. Manzoni' ' , Via dell' Eremo 9/11, 23900, Lecco (Italy); Roca, Isabel [Division of Nuclear Medicine, Hospital Universitari Vall Hebron, 08035, Barcelona (Spain)

    2004-06-01

    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.)

  8. Trastuzumab use during pregnancy: long-term survival after locally advanced breast cancer and long-term infant follow-up.

    Science.gov (United States)

    Andrade, Jurandyr M de; Brito, Luiz G O; Moises, Elaine C D; Amorim, Andréa C; Rapatoni, Liane; Carrara, Hélio H A; Tiezzi, Daniel G

    2016-04-01

    Here, we describe the case of a patient diagnosed with locally advanced breast cancer 8 years ago. Her treatment course was neoadjuvant chemotherapy, followed by mastectomy and then adjuvant radiotherapy and trastuzumab (TTZ). During the use of adjuvant targeted therapy, an incidental pregnancy was diagnosed. Four years later, she developed bone and cerebral metastases, and since then, she has received courses of TTZ, capecitabine, lapatinib, and radiotherapy with intermittent control of the disease. Her 7-year-old son presents a normal physical and long-term neurological developmental curve according to specialized evaluation. This case is unique for several reasons: the patient received the highest dose of TTZ yet described during pregnancy (4400 mg); there has been a long period of disease-free survival after treatment for locally advanced breast cancer and long overall survival despite successive disease progressions during the metastatic phase of the disease (97 months), and there was a monitored pediatric follow-up period (7 years).

  9. Gene aberrations of RRM1 and RRM2B and outcome of advanced breast cancer after treatment with docetaxel with or without gemcitabine

    DEFF Research Database (Denmark)

    Jørgensen, Charlotte Lt; Ejlertsen, Bent; Bjerre, Karsten D

    2013-01-01

    of the hypothesis that aberrations of RRM1 or RRM2B, neither individually nor in combination, are associated with an altered clinical outcome following chemotherapy with gemcitabine in combination with docetaxel compared to docetaxel alone in advanced breast cancer patients....... agent docetaxel in advanced breast cancer patients. Methods Primary tumor samples from patients randomly assigned to gemcitabine plus docetaxel or docetaxel alone were analyzed for RRM1 and RRM2B copy number changes using Fluorescence In Situ Hybridization (FISH) technology with probes covering...... endpoint. Overall survival (OS) and response rate (RR) were secondary endpoints. Associations between RRM1/CEN-11 and/or RRM2B/CEN-8 ratios and time-to-event endpoints were analyzed by unadjusted and adjusted Cox proportional hazards regression models. Heterogeneity of treatment effects on TTP and OS...

  10. The Long-HER Study: Clinical and Molecular Analysis of Patients with HER2+ Advanced Breast Cancer Who Become Long-Term Survivors with Trastuzumab-Based Therapy

    Science.gov (United States)

    Gámez-Pozo, Angelo; Pérez Carrión, Ramón M.; Manso, Luis; Crespo, Carmen; Mendiola, Cesar; López-Vacas, Rocío; Berges-Soria, Julia; López, Isabel Álvarez; Margeli, Mireia; Calero, Juan L. Bayo; Farre, Xavier González; Santaballa, Ana; Ciruelos, Eva M.; Afonso, Ruth; Lao, Juan; Catalán, Gustavo; Gallego, José V. Álvarez; López, José Miramón; Bofill, Francisco J. Salvador; Borrego, Manuel Ruiz; Espinosa, Enrique; Vara, Juan A. Fresno; Zamora, Pilar

    2014-01-01

    Background Trastuzumab improves survival outcomes in patients with HER2+ metastatic breast cancer. The Long-Her study was designed to identify clinical and molecular markers that could differentiate long-term survivors from patients having early progression after trastuzumab treatment. Methods Data were collected from women with HER2-positive metastatic breast cancer treated with trastuzumab that experienced a response or stable disease during at least 3 years. Patients having a progression in the first year of therapy with trastuzumab were used as a control. Genes related with trastuzumab resistance were identified and investigated for network and gene functional interrelation. Models predicting poor response to trastuzumab were constructed and evaluated. Finally, a mutational status analysis of selected genes was performed in HER2 positive breast cancer samples. Results 103 patients were registered in the Long-HER study, of whom 71 had obtained a durable complete response. Median age was 58 years. Metastatic disease was diagnosed after a median of 24.7 months since primary diagnosis. Metastases were present in the liver (25%), lungs (25%), bones (23%) and soft tissues (23%), with 20% of patients having multiple locations of metastases. Median duration of response was 55 months. The molecular analysis included 35 patients from the group with complete response and 18 patients in a control poor-response group. Absence of trastuzumab as part of adjuvant therapy was the only clinical factor associated with long-term survival. Gene ontology analysis demonstrated that PI3K pathway was associated with poor response to trastuzumab-based therapy: tumours in the control group usually had four or five alterations in this pathway, whereas tumours in the Long-HER group had two alterations at most. Conclusions Trastuzumab may provide a substantial long-term survival benefit in a selected group of patients. Whole genome expression analysis comparing long-term survivors vs. a

  11. The Long-HER study: clinical and molecular analysis of patients with HER2+ advanced breast cancer who become long-term survivors with trastuzumab-based therapy.

    Directory of Open Access Journals (Sweden)

    Angelo Gámez-Pozo

    Full Text Available BACKGROUND: Trastuzumab improves survival outcomes in patients with HER2+ metastatic breast cancer. The Long-Her study was designed to identify clinical and molecular markers that could differentiate long-term survivors from patients having early progression after trastuzumab treatment. METHODS: Data were collected from women with HER2-positive metastatic breast cancer treated with trastuzumab that experienced a response or stable disease during at least 3 years. Patients having a progression in the first year of therapy with trastuzumab were used as a control. Genes related with trastuzumab resistance were identified and investigated for network and gene functional interrelation. Models predicting poor response to trastuzumab were constructed and evaluated. Finally, a mutational status analysis of selected genes was performed in HER2 positive breast cancer samples. RESULTS: 103 patients were registered in the Long-HER study, of whom 71 had obtained a durable complete response. Median age was 58 years. Metastatic disease was diagnosed after a median of 24.7 months since primary diagnosis. Metastases were present in the liver (25%, lungs (25%, bones (23% and soft tissues (23%, with 20% of patients having multiple locations of metastases. Median duration of response was 55 months. The molecular analysis included 35 patients from the group with complete response and 18 patients in a control poor-response group. Absence of trastuzumab as part of adjuvant therapy was the only clinical factor associated with long-term survival. Gene ontology analysis demonstrated that PI3K pathway was associated with poor response to trastuzumab-based therapy: tumours in the control group usually had four or five alterations in this pathway, whereas tumours in the Long-HER group had two alterations at most. CONCLUSIONS: Trastuzumab may provide a substantial long-term survival benefit in a selected group of patients. Whole genome expression analysis comparing long

  12. Aluminium in human breast tissue.

    Science.gov (United States)

    Exley, Christopher; Charles, Lisa M; Barr, Lester; Martin, Claire; Polwart, Anthony; Darbre, Philippa D

    2007-09-01

    Aluminium is omnipresent in everyday life and increased exposure is resulting in a burgeoning body burden of this non-essential metal. Personal care products are potential contributors to the body burden of aluminium and recent evidence has linked breast cancer with aluminium-based antiperspirants. We have used graphite furnace atomic absorption spectrometry (GFAAS) to measure the aluminium content in breast biopsies obtained following mastectomies. The aluminium content of breast tissue and breast tissue fat were in the range 4-437 nmol/g dry wt. and 3-192 nmol/g oil, respectively. The aluminium content of breast tissue in the outer regions (axilla and lateral) was significantly higher (P=0.033) than the inner regions (middle and medial) of the breast. Whether differences in the regional distribution of aluminium in the breast are related to the known higher incidence of tumours in the outer upper quadrant of the breast remains to be ascertained.

  13. 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...

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

    Science.gov (United States)

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

    2016-03-01

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

  15. 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.

  16. Evaluation of the prognosis as well as tumor marker levels and immune function of Fuzheng Xiaoliu decoction combined with paclitaxel treatment of advanced breast cancer

    Institute of Scientific and Technical Information of China (English)

    Hai-Ping Huang; Jin-Ru Zhang; Xiao-Fang Li; Jian-Guo Wang

    2016-01-01

    Objective:To analyze the effect of Fuzheng Xiaoliu decoction combined with paclitaxel treatment of advanced breast cancer on the prognosis as well as tumor marker levels, immune function and so on.Methods:A total of 40 patients with advanced breast cancer were randomly divided into observation group and control group (n=20), control group received conventional chemotherapy + paclitaxel treatment and observation group received conventional chemotherapy + paclitaxel + Fuzheng Xiaoliu decoction treatment. The survival of two groups of patients was followed up, and serum levels of tumor markers and sex hormones as well as immune function indexes were determined.Results:Progression-free survival and overall survival of observation group were longer than those of control group; after one course of treatment, serum VEGF-A, TK1, IGF-1, CerbB-2, CEA, CA15-3, CA125, E1 and E2 levels of observation group were significantly lower than those of control group while LH and FSH levels were significantly higher than those of control group; CD3+CD4+, CD8+CD28+, CD19+ and CD16+CD56+ expression levels in peripheral blood of observation group were significantly higher than those of control group while CD4+CD25+ and CD8+CD28- expression levels were significantly lower than those of control group.Conclusion:Fuzheng Xiaoliu decoction combined paclitaxel treatment of advanced breast cancer can reduce tumor malignancy and improve the body's immune function, and is of positive significance in optimizing treatment prognosis.

  17. Association of Type 2 Diabetes Susceptibility Variants With Advanced Prostate Cancer Risk in the Breast and Prostate Cancer Cohort Consortium

    Science.gov (United States)

    Machiela, Mitchell J.; Lindström, Sara; Allen, Naomi E.; Haiman, Christopher A.; Albanes, Demetrius; Barricarte, Aurelio; Berndt, Sonja I.; Bueno-de-Mesquita, H. Bas; Chanock, Stephen; Gaziano, J. Michael; Gapstur, Susan M.; Giovannucci, Edward; Henderson, Brian E.; Jacobs, Eric J.; Kolonel, Laurence N.; Krogh, Vittorio; Ma, Jing; Stampfer, Meir J.; Stevens, Victoria L.; Stram, Daniel O.; Tjønneland, Anne; Travis, Ruth; Willett, Walter C.; Hunter, David J.; Le Marchand, Loic; Kraft, Peter

    2012-01-01

    Observational studies have found an inverse association between type 2 diabetes (T2D) and prostate cancer (PCa), and genome-wide association studies have found common variants near 3 loci associated with both diseases. The authors examined whether a genetic background that favors T2D is associated with risk of advanced PCa. Data from the National Cancer Institute's Breast and Prostate Cancer Cohort Consortium, a genome-wide association study of 2,782 advanced PCa cases and 4,458 controls, were used to evaluate whether individual single nucleotide polymorphisms or aggregations of these 36 T2D susceptibility loci are associated with PCa. Ten T2D markers near 9 loci (NOTCH2, ADCY5, JAZF1, CDKN2A/B, TCF7L2, KCNQ1, MTNR1B, FTO, and HNF1B) were nominally associated with PCa (P < 0.05); the association for single nucleotide polymorphism rs757210 at the HNF1B locus was significant when multiple comparisons were accounted for (adjusted P = 0.001). Genetic risk scores weighted by the T2D log odds ratio and multilocus kernel tests also indicated a significant relation between T2D variants and PCa risk. A mediation analysis of 9,065 PCa cases and 9,526 controls failed to produce evidence that diabetes mediates the association of the HNF1B locus with PCa risk. These data suggest a shared genetic component between T2D and PCa and add to the evidence for an interrelation between these diseases. PMID:23193118

  18. Parametric optimization for tumour identification: bioheat equation using ANOVA and the Taguchi method.

    Science.gov (United States)

    Sudharsan, N M; Ng, E Y

    2000-01-01

    Breast cancer is the number one killer disease among women. It is known that early detection of a tumour ensures better prognosis and higher survival rate. In this paper an intelligent, inexpensive and non-invasive diagnostic tool is developed for aiding breast cancer detection objectively. This tool is based on thermographic scanning of the breast surface in conjunction with numerical simulation of the breast using the bioheat equation. The medical applications of thermographic scanning make use of the skin temperature as an indication of an underlying pathological process. The thermal pattern over a breast tumour reflects the vascular reaction to the abnormality. Hence an abnormal temperature pattern may be an indicator of an underlying tumour. Seven important parameters are identified and analysis of variance (ANOVA) is performed using a 2n design (n = number of parameters, 7). The effect and importance of the various parameters are analysed. Based on the above 2(7) design, the Taguchi method is used to optimize the parameters in order to ensure the signal from the tumour maximized compared with the noise from the other factors. The model predicts that the ideal setting for capturing the signal from the tumour is when the patient is at basal metabolic activity with a correspondingly lower subcutaneous perfusion in a low temperature environment.

  19. Malignant salivary gland tumours

    Energy Technology Data Exchange (ETDEWEB)

    Thompson, S.H. (University of the Witwatersrand, Johannesburg (South Africa). Dept. of Oral Pathology)

    1982-08-01

    The most frequent malignant salivary gland tumours are the mucoepidermoid tumour, adenoid cystic carcinoma and adenocarcinoma. The major salivary glands and the minor glands of the mouth and upper respiratory tract may potentially develop any of these malignant lesions. Malignant lesions most frequently present as a palpable mass and tend to enlarge more rapidly than benign neoplasms. Pain, paresthesia, muscle paralysis and fixation to surrounding tissue are all ominous signs and symptoms. The only reliable means of differential diagnosis of these lesions is biopsy and histologic analysis. Therapy involves surgery or a combination of surgery and radiation therapy. The ultimate prognosis is governed by the intrinsic biologic behaviour of the neoplasms, the extent of disease and adequate clinical therapy.

  20. Dynamic Contrast-Enhanced MR Imaging in a Phase Ⅱ Study on Neoadjuvant Chemotherapy Combining Rh-Endostatin with Docetaxel and Epirubicin for Locally Advanced Breast Cancer

    Directory of Open Access Journals (Sweden)

    Qianxin Jia, Junqing Xu, Weifeng Jiang, Minwen Zheng, Mengqi Wei, Jianghao Chen, Ling Wang, Yi Huan

    2013-01-01

    Full Text Available Background: Anti-angiogenesis is a promising therapeutic strategy for locally advanced breast cancer. We performed this phase II trial to evaluate the anti-angiogenesis and anti-tumor effect of rh-endostatin combined with docetaxel and epirubicin in patients with locally advanced breast cancer by dynamic contrast-enhanced magnetic resonance imaging in 70 previously untreated locally advanced breast cancer patients.Methods: The study population was randomly assigned to neoadjuvant chemotherapy with docetaxel and epirubicin (neoadjuvant chemotherapy group or neoadjuvant chemotherapy combining rh-endostatin with docetaxel and epirubicin (neoadjuvant chemotherapy+rh-endostatin group. The anti-angiogenic and anti-tumor effects of both regimens were evaluated by serial dynamic contrast-enhanced magnetic resonance imaging and microvessel density measurements after final surgery.Results: The results suggested a higher clinical objective response (90.9% vs. 67.7%, P = 0.021 and greater reductions in tumor size (67.2% vs. 55.9%, P = 0.000, Ki-67 proliferation index (32.79% vs. 12.47%, P = 0.000, tumor signal enhanced ratio (64% vs. 48%, P = 0.018, and Ktrans (67% vs. 39%, P = 0.026 in neoadjuvant chemotherapy+rh-endostatin group than those in neoadjuvant chemotherapy group. In addition, the microvessel density value in the neoadjuvant chemotherapy+rh-endostatin group was significantly lower than in the neoadjuvant chemotherapy group (18.67 ± 6.53 vs. 36.05 ± 9.64, P = 0.000. Moreover, the microvessel density value was significantly correlated with Ktrans after neoadjuvant chemotherapy+rh-endostatin treatment (r=0.88, P = 0.00.Conclusions: The neoadjuvant chemotherapy+rh-endostatin treatment significantly repressed angiogenesis in locally advanced breast cancer and synergistically enhanced the anti-tumor effect of neoadjuvant chemotherapy. Serial dynamic contrast-enhanced magnetic resonance imaging data including reductions in tumor size and Ktrans

  1. Breast Conservation Surgery: State of the Art

    Directory of Open Access Journals (Sweden)

    Jonathan White

    2011-01-01

    Full Text Available 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 multicentric breast cancer. The role of novel techniques, such as endoscopic breast surgery and radiofrequency ablation, is yet to be precisely defined.

  2. Zinc isotopic compositions of breast cancer tissue.

    Science.gov (United States)

    Larner, Fiona; Woodley, Laura N; Shousha, Sami; Moyes, Ashley; Humphreys-Williams, Emma; Strekopytov, Stanislav; Halliday, Alex N; Rehkämper, Mark; Coombes, R Charles

    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 isotopic lightness in tumours suggests that sulphur rich metallothionein dominates the isotopic selectivity of a breast tissue cell, rather than Zn-specific proteins. This reveals a possible mechanism of Zn delivery to Zn-sequestering vesicles by metallothionein, and is supported by a similar signature observed in the copper isotopic compositions of one breast cancer patient. This change in intrinsic isotopic compositions due to cancer has the potential to provide a novel early biomarker for breast cancer.

  3. Design and characterization of HER-2-targeted gold nanoparticles for enhanced X-radiation treatment of locally advanced breast cancer.

    Science.gov (United States)

    Chattopadhyay, Niladri; Cai, Zhongli; Pignol, Jean-Philippe; Keller, Brian; Lechtman, Eli; Bendayan, Reina; Reilly, Raymond M

    2010-12-06

    Our purpose was to develop a human epidermal growth factor receptor-2 (HER-2) targeted nanotechnology-based radiosensitizer. HER-2 is overexpressed in 20-30% of all breast cancers and up to 2-fold higher in locally advanced disease (LABC). Trastuzumab was derivatized with a polyethylene glycol (OPSS-PEG-SVA) cross-linker to produce trastuzumab-PEG-OPSS. These immunoconjugates were analyzed by SDS-PAGE, and their immunoreactivity was assessed by flow cytometry using HER-2 overexpressing SK-BR-3 breast cancer cells. Reacting trastuzumab with increasing ratios of PEG resulted in an increase in molecular weight from approximately 148 kDa to 243 kDa, associated with increasing PEG substitution (0.6 to 18.9 PEG chains per trastuzumab). Attachment of approximately 7 PEG chains per trastuzumab resulted in 56% retention in immunoreactivity assessed by flow cytometry. The conjugates were then linked to 30 nm AuNPs. Using a novel (123)iodine-radiotracer based assay that overcomes the current limitations of spectrophotometric quantification of biological molecules on AuNPs we estimate 14.3 ± 2.7 antibodies were attached to each AuNP when 2 × 10(11) AuNPs were reacted with 20 μg of trastuzumab-PEG-OPSS. Specificity of trastuzumab-PEG-AuNPs for HER-2 and internalization in SK-BR-3 cells was demonstrated by comparing the uptake of trastuzumab-PEG-AuNPs or PEG-AuNPs by darkfield microscopy. The ability of trastuzumab-PEG-AuNPs in combination with 300 kVp X-rays to enhance DNA double strand breaks (DSBs) in SK-BR-3 cells was assessed by immunofluorescence using the γ-H2AX assay. γ-H2AX assay results revealed 5.1-fold higher DNA-DSBs with trastuzumab-PEG-AuNPs and X-radiation as compared to treatment with X-radiation alone. The trastuzumab-PEG-AuNPs are a promising targeted nanotechnology-based radiosensitizer for improving LABC therapy. The design and systematic approaches taken to surface modify and characterize trastuzumab-PEG-AuNPs described in this study would have

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

    Directory of Open Access Journals (Sweden)

    Bangaly Traoré

    2015-01-01

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

  5. [Breast self-examination as main technique for breast cancer prevention].

    Science.gov (United States)

    Guerrero Mercedes, Rocío; Llamas Muñoz, M Carmen

    2013-04-01

    Breast cancer is the most common malignancy in women. Breast self-examination stands out as the main preventive measure, since almost 95% of breast tumours are detected by the woman herself through this technique. Nursing is the group most closely related to health education appropriate guidelines to perform the technique correctly: monthly technical realization, recognition of abnormalities in the breast, go to the doctor for possible doubt about changes in them, etc.

  6. Clinical impact of IMPORT HIGH trial (CRUK/06/003) on breast radiotherapy practices in the United Kingdom

    Science.gov (United States)

    Ciurlionis, Laura; Kirby, Anna M; Locke, Imogen; Venables, Karen; Yarnold, John R; Titley, Jenny; Bliss, Judith; Coles, Charlotte E

    2015-01-01

    Objective: IMPORT HIGH is a multicentre randomized UK trial testing dose-escalated intensity-modulated radiotherapy (IMRT) after tumour excision in females with early breast cancer and higher than average local recurrence risk. A survey was carried out to investigate the impact of this trial on the adoption of advanced breast radiotherapy (RT) techniques in the UK. Methods: A questionnaire was sent to all 26 IMPORT HIGH recruiting RT centres to determine whether the trial has influenced non-trial breast RT techniques in terms of volume delineation, dosimetry, treatment delivery and verification. In order to compare the clinical practice of breast RT between IMPORT HIGH and non–IMPORT HIGH centres, parts of the Royal College of Radiologists (RCR) breast RT audit result were used in this study. Results: 26/26 participating centres completed the questionnaire. After joining the trial, the number of centres routinely using tumour bed clips to guide whole-breast RT rose from 5 (19%) to 21 (81%). 20/26 (77%) centres now contour target volumes and organs at risk (OARs) in some or all patients compared with 14 (54%) before the trial. 14/26 (54%) centres offer inverse-planned IMRT for selected non-trial patients with breast cancer, and 10/14 (71%) have adopted the IMPORT HIGH trial protocol for target volume and OARs dose constraints. Only 2/26 (8%) centres used clip information routinely for breast treatment verification prior to IMPORT HIGH, a minority that has since risen to 7/26 (27%). Data on 1386 patients was included from the RCR audit. This suggested that more cases from IMPORT HIGH centres had surgical clips implanted (83 vs 67%), were treated using CT guided planning with full three-dimensional dose compensation (100 vs 75%), and were treated with photon boost RT (30 vs 8%). Conclusion: The study suggests that participation in the IMPORT HIGH trial has played an important part in providing the guidance and support networks needed for the safe integration of

  7. Breast Cancer and Infertility

    OpenAIRE

    2015-01-01

    Breast cancer is the most common malignancy among women and may accompany infertility. The relationship between infertility treatment and breast cancer has not yet been proven. However, estrogen exposure is well known to cause breast cancer. Recent advances in treatment options have provided young patients with breast cancer a chance of being mother [Archives Medical Review Journal 2015; 24(3.000): 317-323

  8. ANALYSIS OF TUMOUR LENGTH AND CLINICOPATHOLOGICAL FEATURES IN CARCINOMA OESOPHAGUS

    Directory of Open Access Journals (Sweden)

    Pampanagouda

    2016-06-01

    Full Text Available Even with multidisciplinary team approach, the prognosis of Oesophageal Cancer (EC has not significantly changed. Studies are required to explore the other prognostic factors, which might alter the outcome. Our study aims at correlating the oesophageal tumour length with stage of the disease and analyse the clinicopathological features. METHODS 150 patients with oesophageal carcinoma (ca who underwent curative surgery without neoadjuvant chemotherapy and/or radiotherapy are included in the study. Formalin fixed oesophageal tumour length was measured. Tumour length was analysed with respect to overall stage, T stage and N stage of the disease. Clinicopathological characteristics were studied. RESULTS From our study correlating tumour length with stage and lymph node involvement, it is observed that there is no linear association with stage of the disease. Squamous cell carcinoma is the predominant histology and lower third was the site most affected. Even though most of the patients still present at an advanced stage, patients with adenocarcinoma presented earlier than squamous cell carcinoma patients. CONCLUSION As there is no proportionate increase in stage of disease with increase in length of tumour, oesophageal tumour length may not be an appropriate prognostic factor. Further well planned studies might bring more evidence on this aspect with respect to impact of tumour length on survival.

  9. PTEN/PIK3CA genes are frequently mutated in spontaneous and medroxyprogesterone acetate-accelerated 7,12-dimethylbenz(a)anthracene-induced mammary tumours of tree shrews.

    Science.gov (United States)

    Xia, Hou-Jun; He, Bao-Li; Wang, Chun-Yan; Zhang, Hai-Lin; Ge, Guang-Zhe; Zhang, Yuan-Xu; Lv, Long-Bao; Jiao, Jian-Lin; Chen, Ceshi

    2014-12-01

    Tree shrew has increasingly become an attractive experimental animal model for human diseases, particularly for breast cancer due to spontaneous breast tumours and their close relationship to primates and by extension to humans. However, neither normal mammary glands nor breast tumours have been well characterised in the Chinese tree shrew (Tupaia belangeri chinensis). In this study, normal mammary glands from four different developmental stages and 18 spontaneous breast tumours were analysed. Haematoxylin and eosin (H&E) staining and immunohistochemistry (IHC) showed that normal mammary gland morphology and structures of tree shrews were quite similar to those found in humans. Spontaneous breast tumours of tree shrews were identified as being intraductal papilloma, papillary carcinoma, and invasive ductal carcinoma with or without lung metastasis. To further analyse breast cancer tumours among tree shrews, 40 3-4 month-old female tree shrews were orally administrated 20 mg 7,12-dimethylbenz(a)anthracene (DMBA) or peanut oil thrice, and then, 15 of these DMBA administrated tree shrews were implanted with medroxyprogesterone acetate (MPA) pellets. DMBA was shown to induce breast tumours (12%) while the addition of MPA increased the tumour incidence (50%). Of these, three induced breast tumours were intraductal papillary carcinomas and one was invasive ductal carcinoma (IDC). The PTEN/PIK3CA (phosphatase and tensin homologue/phosphatidylinositol-4,5-bisphosphate 3-kinase catalytic subunit alpha), but not TP53 and GATA3, genes are frequently mutated in breast tumours, and the PTEN/PIK3CA gene mutation status correlated with the expression of pAKT in tree shrew breast tumours. These results suggest that tree shrews may be a promising animal model for a subset of human breast cancers with PTEN/PIK3CA gene mutations.

  10. A dynamic model for tumour growth and metastasis formation.

    Science.gov (United States)

    Haustein, Volker; Schumacher, Udo

    2012-07-05

    A simple and fast computational model to describe the dynamics of tumour growth and metastasis formation is presented. The model is based on the calculation of successive generations of tumour cells and enables one to describe biologically important entities like tumour volume, time point of 1st metastatic growth or number of metastatic colonies at a given time. The model entirely relies on the chronology of these successive events of the metastatic cascade. The simulation calculations were performed for two embedded growth models to describe the Gompertzian like growth behaviour of tumours. The initial training of the models was carried out using an analytical solution for the size distribution of metastases of a hepatocellular carcinoma. We then show the applicability of our models to clinical data from the Munich Cancer Registry. Growth and dissemination characteristics of metastatic cells originating from cells in the primary breast cancer can be modelled thus showing its ability to perform systematic analyses relevant for clinical breast cancer research and treatment. In particular, our calculations show that generally metastases formation has already been initiated before the primary can be detected clinically.

  11. The hypoxic tumour microenvironment and metastatic progression.

    Science.gov (United States)

    Subarsky, Patrick; Hill, Richard P

    2003-01-01

    The microenvironment of solid tumours contains regions of poor oxygenation and high acidity. Growing evidence from clinical and experimental studies points to a fundamental role for hypoxia in metastatic progression. Prolonged hypoxia increases genomic instability, genomic heterogeneity, and may act as a selective pressure for tumour cell variants. Hypoxia can also act in an epigenetic fashion, altering the expression of genes. Hypoxia-induced changes in gene expression alter non-specific stress responses, anaerobic metabolism, angiogenesis, tissue remodeling, and cell-cell contacts. Experimental studies have demonstrated that inhibition of proteins involved in these processes can modify metastasis formation, suggesting a causal role in metastatic progression. Recent advances in high-throughput screening techniques have allowed identification of many hypoxia-induced genes that are involved in the processes associated with metastasis. Here we review the epigenetic control of gene expression by the hypoxic microenvironment and its potential contribution to metastatic progression.

  12. Vaginal haemangioendothelioma: an unusual tumour.

    LENUS (Irish Health Repository)

    Mohan, H

    2012-02-01

    Vaginal tumours are uncommon and this is a particularly rare case of a vaginal haemangioendothelioma in a 38-year-old woman. Initial presentation consisted of symptoms similar to uterovaginal prolapse with "something coming down". Examination under anaesthesia demonstrated a necrotic anterior vaginal wall tumour. Histology of the lesion revealed a haemangioendothelioma which had some features of haemangiopericytoma. While the natural history of vaginal haemangioendothelioma is uncertain, as a group, they have a propensity for local recurrence. To our knowledge this is the third reported case of a vaginal haemangioendothelioma. Management of this tumour is challenging given the paucity of literature on this tumour. There is a need to add rare tumours to our "knowledge bank" to guide management of these unusual tumours.

  13. Messenger RNA (mRNA) nanoparticle tumour vaccination

    Science.gov (United States)

    Phua, Kyle K. L.; Nair, Smita K.; Leong, Kam W.

    2014-06-01

    Use of mRNA-based vaccines for tumour immunotherapy has gained increasing attention in recent years. A growing number of studies applying nanomedicine concepts to mRNA tumour vaccination show that the mRNA delivered in nanoparticle format can generate a more robust immune response. Advances in the past decade have deepened our understanding of gene delivery barriers, mRNA's biological stability and immunological properties, and support the notion for engineering innovations tailored towards a more efficient mRNA nanoparticle vaccine delivery system. In this review we will first examine the suitability of mRNA for engineering manipulations, followed by discussion of a model framework that highlights the barriers to a robust anti-tumour immunity mediated by mRNA encapsulated in nanoparticles. Finally, by consolidating existing literature on mRNA nanoparticle tumour vaccination within the context of this framework, we aim to identify bottlenecks that can be addressed by future nanoengineering research.

  14. 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.

  15. Primary bone tumours in infants

    Energy Technology Data Exchange (ETDEWEB)

    Kozlowski, K.; Beluffi, G.; Cohen, D.H.; Padovani, J.; Tamaela, L.; Azouz, M.; Bale, P.; Martin, H.C.; Nayanar, V.V.; Arico, M.

    1985-09-01

    Ten cases of primary bone tumours in infants (1 osteosarcoma, 3 Ewing's sarcoma, 1 chondroblastoma and 5 angiomastosis) are reported. All cases of angiomatosis showed characteristic radiographic findings. In all the other tumours the X-ray appearances were different from those usually seen in older children and adolescents. In the auhtors' opinion the precise diagnosis of malignant bone tumours in infancy is very difficult as no characteristic X-ray features are present in this age period.

  16. De novo sequencing of circulating miRNAs identifies novel markers predicting clinical outcome of locally advanced breast cancer

    Directory of Open Access Journals (Sweden)

    Wu Xiwei

    2012-03-01

    Full Text Available Abstract Background MicroRNAs (miRNAs have been recently detected in the circulation of cancer patients, where they are associated with clinical parameters. Discovery profiling of circulating small RNAs has not been reported in breast cancer (BC, and was carried out in this study to identify blood-based small RNA markers of BC clinical outcome. Methods The pre-treatment sera of 42 stage II-III locally advanced and inflammatory BC patients who received neoadjuvant chemotherapy (NCT followed by surgical tumor resection were analyzed for marker identification by deep sequencing all circulating small RNAs. An independent validation cohort of 26 stage II-III BC patients was used to assess the power of identified miRNA markers. Results More than 800 miRNA species were detected in the circulation, and observed patterns showed association with histopathological profiles of BC. Groups of circulating miRNAs differentially associated with ER/PR/HER2 status and inflammatory BC were identified. The relative levels of selected miRNAs measured by PCR showed consistency with their abundance determined by deep sequencing. Two circulating miRNAs, miR-375 and miR-122, exhibited strong correlations with clinical outcomes, including NCT response and relapse with metastatic disease. In the validation cohort, higher levels of circulating miR-122 specifically predicted metastatic recurrence in stage II-III BC patients. Conclusions Our study indicates that certain miRNAs can serve as potential blood-based biomarkers for NCT response, and that miR-122 prevalence in the circulation predicts BC metastasis in early-stage patients. These results may allow optimized chemotherapy treatments and preventive anti-metastasis interventions in future clinical applications.

  17. A combination of paclitaxel and gemcitabine in an intensive dose-dense neoadjuvant chemotherapy schedule for locally advanced breast cancer

    Directory of Open Access Journals (Sweden)

    I. V. Frai

    2011-01-01

    Full Text Available Objective: to improve the results of neoadjuvant chemotherapy (CT in patients with locally advanced (L A inoperable breast cancer (BC at baseline, by using the intensified combination CT at the interval being reduced between the administration of cytostatic dru gs to 2 weeks to give a chance to the patients to be surgically treated.Subjects and methods. The study enrolled 26 patients aged 33 to 75 years with L A BC. Paclitaxel was administered intravenously (IV over 3 hours at a dose of 175 mg/m2 on day 1, followed by gemcitabine, 2000 mg/m2, given by 30-minute IV infusion on day 1 every 2 w eeks. If the cytostatics were well tolerated and their effect increased, the treatment was continued up to 6 courses.Results. Eighteen (69.2% out of the 26 patients achieved the objective effect of treatment; of them 17 (65.4% had a partial remission and 1 (3.8 had a complete remission.The therapeutic pathomorphism of a tumor w as rated in 22 patients; fourth-degree tumor pathomorphism w as found in 2 (9% patien ts. The follow-up of patients w as 11 to 28 months (median, 20 months. The median time to progression w as not reached in the entire group of patients.Conclusion. A combination of paclitaxel and gemcitabine in intensive dose-dense scheduling has a marked antitumor activity in BC andis characterized by its good tolerability without a pronounced myelosuppressive effect. This therapy regimen may be used as neoadjuvant CT.

  18. LET-painting increases tumour control probability in hypoxic tumours.

    Science.gov (United States)

    Bassler, Niels; Toftegaard, Jakob; Lühr, Armin; Sørensen, Brita Singers; Scifoni, Emanuele; Krämer, Michael; Jäkel, Oliver; Mortensen, Lise Saksø; Overgaard, Jens; Petersen, Jørgen B

    2014-01-01

    LET-painting was suggested as a method to overcome tumour hypoxia. In vitro experiments have demonstrated a well-established relationship between the oxygen enhancement ratio (OER) and linear energy transfer (LET), where OER approaches unity for high-LET values. However, high-LET radiation also increases the risk for side effects in normal tissue. LET-painting attempts to restrict high-LET radiation to compartments that are found to be hypoxic, while applying lower LET radiation to normoxic tissues. Methods. Carbon-12 and oxygen-16 ion treatment plans with four fields and with homogeneous dose in the target volume, are applied on an oropharyngeal cancer case with an identified hypoxic entity within the tumour. The target dose is optimised to achieve a tumour control probability (TCP) of 95% when assuming a fully normoxic tissue. Using the same primary particle energy fluence needed for this plan, TCP is recalculated for three cases assuming hypoxia: first, redistributing LET to match the hypoxic structure (LET-painting). Second, plans are recalculated for varying hypoxic tumour volume in order to investigate the threshold volume where TCP can be established. Finally, a slight dose boost (5-20%) is additionally allowed in the hypoxic subvolume to assess its impact on TCP. Results. LET-painting with carbon-12 ions can only achieve tumour control for hypoxic subvolumes smaller than 0.5 cm(3). Using oxygen-16 ions, tumour control can be achieved for tumours with hypoxic subvolumes of up to 1 or 2 cm(3). Tumour control can be achieved for tumours with even larger hypoxic subvolumes, if a slight dose boost is allowed in combination with LET-painting. Conclusion. Our findings clearly indicate that a substantial increase in tumour control can be achieved when applying the LET-painting concept using oxygen-16 ions on hypoxic tumours, ideally with a slight dose boost.

  19. Evaluation of pathomorphological changes and survival after selective intraarterial polychemotherapy of locally advanced breast cancer

    Directory of Open Access Journals (Sweden)

    Bondar G.V.

    2011-01-01

    Full Text Available The pathomorphological changes (pathologic response and survival of patients with locally advanced breastcancer (BC were analyzed for the 89 patients treated with selective intraarterial polychemotherapy (PCT in neoadjuvantmode and 46 treated with intravenous PCT in the same mode (control. More significant pathomorphological response afterthe treatment of BC in the neoadjuvant mode was achieved after selective intra-arterial PCT (p<0,01. In the intraarterial PCTgroup pathomorphosis grade 4 was observed in 16.9% (control – 8.70%, grade 3 – 37,0% (control – 28.3%, grade 2 –46,1% (control – 26,1%. In the control group 1 degree pathomorphosis was in 26.1% of patients, no pathologic response – in10,9%. In patients with pathomorphosis of 2-4 degrees in intraarterial PCT group 5-year survival increases by 0,90-5,60%compared with the control, 10-year-old survival – by 5,60-11,6%. Survival tended to increase with the degree of pathomorphosiswithout statistical differences in groups of intraarterial and intravenous PCT for each year of observation. The averagelife expectancy for the intraarterial PCT group was 4,61±0,02 years, for the control group – 4,19±0,05 (p<0,001. For 1-7years difference in survival was within 5,8-9,5%. The best results are observed after seventh year: 7-10-year survival inintraarterial PCT group was 38.2%, in the control group – 23,9%.

  20. Retrospective study of neoadjuvant versus adjuvant radiochemotherapy in locally advanced noninflammatory breast cancer. Survival advantage in cT2 category by neoadjuvant radiochemotherapy

    Energy Technology Data Exchange (ETDEWEB)

    Roth, Stephan Ludwig; Lang, Innokentij; Budach, Wilfried [Dept. of Radiotherapy, Univ. of Duesseldorf (Germany); Audretsch, Werner [Breast Center, Marien-Hospital, Duesseldorf (Germany); Bojar, Hans [Inst. for Oncologic Chemistry, Univ. of Duesseldorf (Germany); Willers, Reinhart [Computer Center, Univ. of Duesseldorf (Germany)

    2010-06-15

    Purpose: this retrospective study compares patients treated between 1991 and 1998 with neoadjuvant radiotherapy {+-} chemotherapy (RCT) or adjuvant RCT for locally advanced noninflammatory breast cancers (LABC) in terms of pathologic complete response (pCR), 10-year relapse-free (RFS), and overall survival (OS). Patients and methods: preoperative RCT in 315 and adjuvant RCT in 329 cases consisted in 50 Gy (5 x 2 Gy/week) to the breast and the supra-/infraclavicular lymph nodes. 101 neoadjuvant patients received - in case of breast conservation - a 10-Gy interstitial boost with {sup 192}Ir afterloading before and 214 neoadjuvant patients a preoperative electron boost after external-beam radiotherapy. In the neoadjuvant RCT group, chemotherapy was applied prior to radiotherapy in 192 patients, and simultaneously in 113; ten had no chemotherapy. In the adjuvant RCT group, chemotherapy was applied to 44 patients before surgery and to 166 after surgery; 119 had no chemotherapy. Results: breast conservation became possible in 50.8% after neoadjuvant RCT for LABC with a pCR rate at surgery of 29.2%. A complete nodal remission (pNO) after RCT was observed in 56% (89/159) of the cN+ (clinically node-positive) neoadjuvant patients. There were trends in favor of preoperative RCT for RFS and OS (hazard ratio [HR] = 0.85; p = 0.09 for RFS; HR = 0.8130; p = 0.1037 for OS). For patients with cT2 tumors the RFS and OS were statistically significantly better (HR = 0.5090; p = 0.0130 for RFS; HR = 0.4390; p = 0.0026 for OS) after neoadjuvant compared to adjuvant RCT. Conclusion: neoadjuvant RCT achieved a pCR rate of 29.2% and a statistically significantly better RFS and OS in patients with cT2-category breast cancer. (orig.)

  1. Proteomic maps of breast cancer subtypes

    DEFF Research Database (Denmark)

    Tyanova, Stefka; Albrechtsen, Reidar; Kronqvist, Pauliina

    2016-01-01

    oestrogen receptor positive (luminal), Her2 positive and triple negative breast tumours and reached a quantitative depth of >10,000 proteins. These proteomic profiles identified functional differences between breast cancer subtypes, related to energy metabolism, cell growth, mRNA translation and cell...

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

    Science.gov (United States)

    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 were used to develop a discrete choice experiment questionnaire. Each questionnaire was composed of seven choice sets and each choice set contained those four attributes with different levels. Breast cancer patients were asked to choose one treatment alternative in each choice set. Multinomial logit model was used to determine relative preferences of each attribute and the WTP for all attributes and treatments were calculated. A total of 146 patients were included in study analyses. Results showed that the patients preferred treatments with higher PFS and lower side effects. The patients were willing to pay US$151.6, US$69.8, and US$278.3 per month in exchange for every 1 month increase in PFS and every 1 % decreased risk of anemia and pneumonitis, respectively. The patients were willing to pay for exemestane and exemestane plus everolimus US$551.8 and US$414.2 per month, respectively. In conclusion, patients weighted importance on PFS, anemia, and pneumonitis, when they needed to choose an aromatase inhibitor plus mammalian target of rapamycin (mTOR) inhibitor for advanced breast cancer treatments after failure of standard treatments. They valued exemestane alone more than exemestane plus everolimus.

  3. Prognostic studies of canine and feline mammary tumours: the need for standardized procedures.

    Science.gov (United States)

    Matos, A J F; Baptista, C S; Gärtner, M F; Rutteman, G R

    2012-07-01

    For several years, veterinary oncologists have been struggling with the prognosis of mammary tumours in dogs and cats. Translation of tumour characteristics into prognostic information is an invaluable tool for the use of the most appropriate therapies, as well as for planning innovative therapeutic trials. Moreover, canine and feline spontaneous mammary gland tumours are good models for the study of human breast cancer. Collecting and interpreting information regarding the prognosis of canine and feline mammary tumours is difficult due to the fact that different methods have been applied to study various components and characteristics. This review identifies some of the challenges of prognostic studies of spontaneous canine and feline mammary tumours and suggests standardized procedures to overcome these challenges and facilitate reproducibility and assessment of results.

  4. Recent advances in molecular pathology of phyllodes tumor of breast%乳腺叶状肿瘤分子遗传学与分子病理学研究进展

    Institute of Scientific and Technical Information of China (English)

    牛昀

    2011-01-01

    @@ 乳腺叶状肿瘤(Breast phyllodes tumours,BPT)[1-2]是一种病理形态和临床表现颇具特征的纤维上皮混合性肿瘤.有些研究者力求从组织学和细胞学特征方面来预测手术后局部复发的可能,但这些形态学标准往往受主观因素影响较多.

  5. ΔNp63 promotes stem cell activity in mammary gland development and basal-like breast cancer by enhancing Fzd7 expression and Wnt signalling.

    Science.gov (United States)

    Chakrabarti, Rumela; Wei, Yong; Hwang, Julie; Hang, Xiang; Andres Blanco, Mario; Choudhury, Abrar; Tiede, Benjamin; Romano, Rose-Anne; DeCoste, Christina; Mercatali, Laura; Ibrahim, Toni; Amadori, Dino; Kannan, Nagarajan; Eaves, Connie J; Sinha, Satrajit; Kang, Yibin

    2014-10-01

    Emerging evidence suggests that cancer is populated and maintained by tumour-initiating cells (TICs) with stem-like properties similar to those of adult tissue stem cells. Despite recent advances, the molecular regulatory mechanisms that may be shared between normal and malignant stem cells remain poorly understood. Here we show that the ΔNp63 isoform of the Trp63 transcription factor promotes normal mammary stem cell (MaSC) activity by increasing the expression of the Wnt receptor Fzd7, thereby enhancing Wnt signalling. Importantly, Fzd7-dependent enhancement of Wnt signalling by ΔNp63 also governs tumour-initiating activity of the basal subtype of breast cancer. These findings establish ΔNp63 as a key regulator of stem cells in both normal and malignant mammary tissues and provide direct evidence that breast cancer TICs and normal MaSCs share common regulatory mechanisms.

  6. HER2 Amplification Has no Prognostic Value in Sporadic and Hereditary Ovarian Tumours

    Directory of Open Access Journals (Sweden)

    Brożek Izabela

    2006-11-01

    Full Text Available Abstract Whereas HER2 amplification is a well-known phenomenon in breast tumours, its frequency and clinical importance in ovarian cancer have not been established. The aim of the study was to compare the frequency of HER2 amplification in hereditary (BRCA-positive and sporadic (BRCA-negative ovarian tumours and to estimate the association of this gene alteration on clinical outcome in ovarian cancer patients. We analysed HER2 amplification in 53 ovarian tumours: 20 from mutation carriers (18 in BRCA1 and 2 in BRCA2 gene and 33 from non-carriers. Fluorescence in situ hybridization for HER2 was performed on 'touch' slides from frozen tumour samples or formalin-fixed, paraffin-embedded tissue. Our results indicate that high amplification (HER2: centromere ratio>5 is an infrequent phenomenon in ovarian tumours (6/53 cases. It occurs in both hereditary (4/20 and sporadic (2/33 tumours and no difference in the frequency of HER2 amplification exists between these groups. There is no significant difference in the clinical outcome of patients with HER2 amplified and non-amplified tumours (p = 0.3. Our results suggest a different biological role of HER2 amplification in ovarian and breast cancer.

  7. Clinical overview of metronomic chemotherapy in breast cancer.

    Science.gov (United States)

    Munzone, Elisabetta; Colleoni, Marco

    2015-11-01

    Over 15 years ago, low-dose metronomic chemotherapy was shown to induce disease control in patients with advanced-stage breast cancer with a lower incidence of adverse events compared with conventional maximum tolerated dose chemotherapy. Good response rates have been seen in heavily pre-treated patients for whom limited treatment options are available. Most patients prefer oral therapy and metronomic chemotherapy is a convenient alternative in patients with advanced-stage disease in which minimal toxicity and good tumour control are the overall aims of treatment. The addition of metronomic protocols to standard neoadjuvant chemotherapy regimens has produced promising pathological complete response rates. Ongoing trials including the SYSUCC-001 trial in patients with triple-negative breast cancer and the IBCSG 22-00 trial that is assessing a cyclophosphamide-methotrexate maintenance regimen after standard adjuvant therapy in hormone receptor-negative disease, will clarify the value of adding this approach to conventional therapies. The low cost associated with metronomic chemotherapy represents an opportunity for the utilization of this treatment option, especially in developing countries, and poses a challenge for the launch of large trials sponsored by industry. Using breast cancer as the principal example, we discuss the key clinical advances in this area, including new trial design, appropriate patient and end point selection, as well as the evolving rationale for metronomic chemotherapy combinations.

  8. A software tool based on the Surface Evolver for precise location of tumours as a preoperative procedure to partial mastectomy

    Science.gov (United States)

    Elias Fabris, Antonio; Zanchetta do Nascimento, Marcelo; Ramos Batista, Valério

    2015-09-01

    We present a fast and reliable program that gives precise location of breast tumours for a partial mastectomy. Our program is fully implemented in the Surface Evolver, which is a general-purpose simulator of physical experiments. By starting from the mammograms that show a tumour one takes its 2D coordinates in each view (CC and MLO). These coordinates, together with some measurements of the patient's breast, are given as input to our simulator. From this point on the simulator reproduces all main steps of taking mammography with a virtual transparent breast that matches the patient's. The virtual mammography procedure is graphically displayed on the computer screen, so that users can track the virtual tumour inside the breast. As output we have the coordinates of the tumour position when the woman lies on the operating table for the surgery. With these coordinates the surgeon can make a small incision into the breast and reach the tumour for its removal. The whole structure of the breast is preserved after a simple plastic correction.

  9. Advancing Our Understanding of the Etiologies and Mutational Landscapes of Basal-Like, Luminal A, and Luminal B Breast Cancers

    Science.gov (United States)

    2014-10-01

    University of Michigan Michigan Center for Translational Pathology 5309 CCC 1400 E. Medical Center Drive Ann Arbor, MI 48109-5940 9...detailed telephone interview, collection of breast tissue and oral samples and medical record abstraction. Breast tissue samples will be reviewed and...tested at Fred Hutchinson Research Center and special tissue analyses will also be performed at the Michigan Center for Translational Pathology . This

  10. Tumours in the Small Bowel

    Directory of Open Access Journals (Sweden)

    N. Kurniawan

    2014-01-01

    Full Text Available Small bowel tumours are rare and originate from a wide variety of benign and malignant entities. Adenocarcinomas are the most frequent primary malignant small bowel tumours. Submucosal tumours like gastrointestinal stromal tumours (GIST or neuroendocrine tumours (NET may show a central umbilication, pathologic vessels, bridging folds or an ulceration of the overlying mucosa. These signs help to differentiate them from harmless bulges caused by impression from outside, e.g. from other intestinal loops. Sarcomas of the small bowel are rare neoplasias with mesenchymal origin, sometimes presenting as protruding masses. Benign tumours like lipoma, fibrolipoma, fibroma, myoma, and heterotopias typically present as submucosal masses. They cannot be differentiated endoscopically from those with malignant potential as GIST or NET. Neuroendocrine carcinomas may present with diffuse infiltration, which may resemble other malignant tumours. The endoscopic appearance of small bowel lymphomas has a great variation from mass lesions to diffuse infiltrative changes. Melanoma metastases are the most frequent metastases to the small bowel. They may be hard to distinguish from other tumours when originating from an amelanotic melanoma.

  11. Stage at diagnosis, clinicopathological and treatment patterns of breast cancer at Bugando Medical Centre in north-western Tanzania.

    Science.gov (United States)

    Mabula, Joseph B; Mchembe, Mabula D; Chalya, Phillipo L; Giiti, Geofrey; Chandika, Alphonce B; Rambau, Peter; Masalu, Nestory; Gilyomai, Japhet M

    2012-10-01

    Breast cancer, although reported to be the commonest female malignancy worldwide has not been extensively studied in north-western Tanzania. The aim of this retrospective review was to describe in our setting, the stage at diagnosis, clinicopathological and treatment patterns among patients with breast cancer. Data were analyzed using SPSS software system. A total of 384 patients were studied. The median age was 45 years (range 21 to 78 years). The male to female ratio was 1: 46.8. Most of the patients were premenopausal (63.8%) and presented late with advanced breast cancer disease. Majority of patients (63.0%) presented with stage III disease. Lymph node and distant metastasis at the time of diagnosis was reported in 70.8% and 21.4% of patients, respectively. Invasive ductal carcinoma (91.7%) was the most frequent histopathological type and most patients (63.8%) had poorly differentiated tumour. Patients with tumour size greater than 6cm had significantly high rate of lymph node metastasis (P=0.001) and presence of necrosis within the tumour (P=0.012) compared to patients with tumour size less than 6cm in diameter. Patients younger than 45 years had significantly high rate of lymph node metastasis compared to the patients above this age (P=0.0 11). Mastectomy was the main modality of treatment that was used in 99.5% of the patients. Adjuvant chemotherapy and radiotherapy was reported in 44.8% and 11.7% of patients, respectively. Hormonal therapy (tamoxifen) was given postoperatively to all patients. The overall five-year survival rate was 21.8%. The age of patient at diagnosis, stage of disease, extent of lymph node involvement and histological grade were found to be independent predictors of overall survival rate (Penlightenment of breast cancer and set up screening centres to encourage early presentations.

  12. Results of a conservative treatment combining induction (neoadjuvant) and consolidation chemotherapy, hormonotherapy, and external and interstitial irradiation in 98 patients with locally advanced breast cancer (IIIA-IIIB)

    Energy Technology Data Exchange (ETDEWEB)

    Jacquillat, C.; Baillet, F.; Weil, M.; Auclerc, G.; Housset, M.; Auclerc, M.; Sellami, M.; Jindani, A.; Thill, L.; Soubrane, C.

    1988-05-15

    Ninety-eight patients with locally advanced breast cancer (Stage IIIA-IIIB) were entered into a pilot study combining intensive induction (neoadjuvant) chemotherapy (VTMFAP) with or without hormonochemotherapy, external and interstitial radiotherapy, and consolidation chemotherapy with or without hormonochemotherapy. Tumor regression over 50% was observed in 91% patients after chemotherapy, and complete clinical remission occurred in 100% patients after irradiation. The rate of local relapse is 13%. The 3-year disease-free survival is 62% and 3-year global survival is 77%. Initial chemotherapeutic tumor regression greater than 75% is the main predictive factor for disease-free survival.

  13. Intraspinal tumours in the Kenya African.

    Science.gov (United States)

    Ruberti, R F; Carmagnani, A L

    1976-06-01

    Thirty-one cases of intraspinal tumours in the African have been described, with age, sex incidence, frequency, site and histopathology shown. Intraspinal tumours in this series are compared with the larger series. Extradural and intramedullary tumours together with cervical spine tumours appear to be more frequent in this series. There is a high incidence of dumbell tumours in the neurinomas. Sarcomas are the most common type of tumours and mainly affect the thoracic spine.

  14. Imatinib treatment for gastrointestinal stromal tumour (GIST).

    Science.gov (United States)

    Lopes, Lisandro F; Bacchi, Carlos E

    2010-01-01

    Gastrointestinal stromal tumour (GIST) is the most common mesenchymal neoplasm of the gastrointestinal tract. GISTs are believed to originate from intersticial cells of Cajal (the pacemaker cells of the gastrointestinal tract) or related stem cells, and are characterized by KIT or platelet-derived growth factor receptor alpha (PDGFRA) activating mutations. The use of imatinib has revolutionized the management of GIST and altered its natural history, substantially improving survival time and delaying disease progression in many patients. The success of imatinib in controlling advanced GIST led to interest in the neoadjuvant and adjuvant use of the drug. The neoadjuvant (preoperative) use of imatinib is recommended to facilitate resection and avoid mutilating surgery by decreasing tumour size, and adjuvant therapy is indicated for patients at high risk of recurrence. The molecular characterization (genotyping) of GISTs has become an essential part of the routine management of the disease as KIT and PDGFRA mutation status predicts the likelihood of achieving response to imatinib. However, the vast majority of patients who initially responded to imatinib will develop tumour progression (secondary resistance). Secondary resistance is often related to secondary KIT or PDGFRA mutations that interfere with drug binding. Multiple novel tyrosine kinase inhibitors may be potentially useful for the treatment of imatinib-resistant GISTs as they interfere with KIT and PDGFRA receptors or with the downstream-signalling proteins.

  15. Unusual tumours of the lung.

    Science.gov (United States)

    Wright, E S; Pike, E; Couves, C M

    1983-09-01

    Unusual lung tumors are not simply pathological curiosities. They demonstrate features of major significance in diagnosis, treatment, and prognosis. Six of these tumours are discussed: (1) Carcinosarcoma is rarely found in the lung. The histogenis of the lesion is unclear and the prognosis is poor. (2) Only three cases of pleomorphic adenoma have previously been described. Differentiation from other "mixed tumours" of the lung is essential. (3) A rare case of bronchial adenoma producing ectopic ACTH is described. Early recognition of these polypeptide hormone-secreting tumours is stressed. (4) Oat cell carcinoma with the myasthenic (Eaton-Lambert) syndrome shows the clinical features which should permit early tumour diagnosis. The hazards of muscle relaxants must be recognized. (5) Prostatic carcinoma with endobronchial metastases is is discussed. The importance of localization of the primary tumour is emphasized. (6) An example of double primary carcinoma is presented. The rarity of this finding may be related to the poor prognosis of patients with bronchogenesis carcinoma.

  16. The p53 pathway in breast cancer

    OpenAIRE

    Gasco, Milena; Shami, Shukri; Crook, Tim

    2002-01-01

    p53 mutation remains the most common genetic change identified in human neoplasia. In breast cancer, p53 mutation is associated with more aggressive disease and worse overall survival. The frequency of mutation in p53 is, however, lower in breast cancer than in other solid tumours. Changes, both genetic and epigenetic, have been identified in regulators of p53 activity and in some downstream transcriptional targets of p53 in breast cancers that express wild-type p53. Molecular pathological an...

  17. Primary osteosarcoma of the breast: case report

    OpenAIRE

    Saber, Boutayeb; Nawal, Ahbeddou; Mohamed, Fetohi; Hassan, Errihani

    2008-01-01

    Mammary sarcomas are very uncommon and make up less than 1% of all primary breast malignancies. Primary osteosarcoma of the breast is extremely rare and represents 12.5% of mammary sarcomas. A secondary lesion from a primary osteosarcoma of the bone should be considered in the differential diagnosis. In addition, the absence of a direct connection between the tumour and the underlying skeleton is mandatory for the diagnosis. We report a case of primary osteosarcoma of the breast occurring in ...

  18. Benign breast diseases. Radiology, pathology, risk assessment. 2. ed.

    Energy Technology Data Exchange (ETDEWEB)

    Chinyama, Catherine N. [Princess Elizabeth Hospital, Le Vauquiedor, St. Martin' s Guernsey, Channel Islands (United Kingdom); Brighton and Sussex Medical School, Brighton (United Kingdom)

    2014-04-01

    Radiological and pathological correlation of the full range of benign breast lesions, with emphasis on screen-detected lesions. Detailed discussion of risk assessment. Revised and updated edition, with a new chapter on gynaecomastia. Ideal aid to the management of patients with benign or indeterminate breast lesions in a multidisciplinary setting. The second edition of this book has been extensively revised and updated. There have been numerous scientific advances in the radiology, pathology and risk assessment of benign breast lesions since the publication of the first edition. The first edition concentrated on screen-detected lesions, which has since been rectified; new symptomatic and screen-detected lesions are discussed in the second edition and include: mastitis and breast abscesses, idiopathic granulomatous mastitis, diabetic mastopathy, phyllodes tumours, gynaecomastia and pseudoangiomatous stromal hyperplasia. The chapters on columnar cell lesions and mucocele-like lesions have been extensively updated. Where applicable, genetic analysis of the benign lesions, which is becoming part of personalised medicine in the field of breast cancer, has been included. The book also presents detailed analyses of the main models, such as the Gail Model, used to assess the subsequent risk of breast cancer in individuals. The current trend in the management of all cancers is preventative. Screening mammography detects early curable cancers as well as indeterminate lesions, the latter of which are invariably pathologically benign. The author has collated important benign lesions and, based on peer-reviewed publications, has documented the relative risk of subsequent cancer to allow the patient and the clinician to implement preventative measures where possible. This book will therefore serve as an essential component of multidisciplinary management of patients with symptomatic and screen-detected benign breast lesions.

  19. TOX3 mutations in breast cancer.

    Directory of Open Access Journals (Sweden)

    James Owain Jones

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

  20. Mystery of bilateral breast masses

    Directory of Open Access Journals (Sweden)

    Nausheen Khan

    2011-12-01

    Full Text Available Leiomyosarcoma (LMS is an uncommon malignant tumour of smooth muscle origin. It arises in the gastro intestinal tract, retroperitoneum, urinary bladder, uterus and soft tissue. Peritoneal leiomyosarcomatosis (PL is defined as a peritoneal dissemination of a primary sarcoma. We present a case of leiomyosarcomatosis with wide spread dissemination including involvement of both breasts.

  1. Combination goserelin and tamoxifen therapy in premenopausal advanced breast cancer: a multicentre study by the ITMO group. Italian Trials in Medical Oncology.

    Science.gov (United States)

    Buzzoni, R.; Biganzoli, L.; Bajetta, E.; Celio, L.; Fornasiero, A.; Mariani, L.; Zilembo, N.; Di Bartolomeo, M.; Di Leo, A.; Arcangeli, G.

    1995-01-01

    It has been suggested that tamoxifen may improve the efficacy of medical castration with luteinising hormone-releasing hormone analogues, but very few data have so far been published concerning the clinical and endocrinological activity of this therapeutic modality. In this phase II multicentre trial conducted by the Italian Trials in Medical Oncology group (ITMO), 64 premenopausal patients with hormone receptor-positive or unknown breast cancer were treated with monthly s.c. injections of goserelin 3.6 mg, in association with a tamoxifen daily dose of 20 mg, as first-line therapy for their advanced disease. All of the patients were evaluable for efficacy and there was an overall response rate of 41% (95% confidence interval 28-52%), with 7 of the 26 responders achieving complete remission. The median time to response was 4 months (range 2-17), and the median response duration was 13 months (range 6-37 +). Better responses were observed in soft tissues (51%); the response in visceral and bone metastases was respectively 19% and 37%. Serum concentrations of gonadotrophins and oestradiol were significantly decreased by the treatment, oestrogen levels being constantly suppressed to within the range observed in post-menopausal women. No significant change was detected in serum testosterone levels. In our experience, although it was not associated with any increased clinical efficacy, the concurrent use of goserelin and tamoxifen proved to be a feasible approach in the management of premenopausal advanced breast cancer. PMID:7734310

  2. Randomized controlled trial in advance stage breast cancer patients for the effectiveness on stress marker and pain through Sudarshan Kriya and Pranayam

    Directory of Open Access Journals (Sweden)

    Neeta Kumar

    2013-01-01

    Full Text Available Objective: The objective of this study is to examine the effect of a cognitive, behavioral stress management module of Sudarshan Kriya (SK and P on levels of serum cortisol and pain among the women suffering from advanced stage breast cancer. Materials and Methods: Participants (n = 147 were screened and randomized to receive standard care (n = 69 versus standard along with SK and Pranayam (P intervention (n = 78 imparted in one 18 hrs workshop spread during 3 days. Participants were expected to practice it at home 20 min daily as adjuvant to standard pharmacological treatment for pain. Results: There was a significant difference in blood cortisol levels after 3 months of practice of SK and P. Mean blood levels in the intervention arm were 341.2 ng/ml against 549.2 ng/ml in the control arm (P ≤ 0.002. Pain perception in comparison to control arm reduced by 3 points in SK and P arm on 0-10 verbal scale of pain. Conclusion: SK and P is an effective intervention in reducing stress and pain among advance stage patients of breast cancer.

  3. Malignant eccrine breast spiradenoma. A case report and literature review

    Directory of Open Access Journals (Sweden)

    Alejandra de Andrés Gómez

    2015-01-01

    Conclusion: Eccrine spiradenomas are rare adnexal tumours of the skin. Intraparenquimatous breast location is especially infrequent. Diagnosis is based on histopathological examination. MES metastasizes (40%, so a close follow up is recommended.

  4. Advances in Variations of Estrogen Receptor, Progesterone Receptor and Human Epidermal Growth Factor Receptor-2 Status in Metastatic Breast Cancer

    Institute of Scientific and Technical Information of China (English)

    Yuan Yuan; Zhang Lili

    2013-01-01

    Chemotherapy, endocrine therapy and molecular targeted therapy are vital means in the treatment of metastatic breast cancer (MBC), whose reasonable and standard applications are of great importance to prolong patients’ survival and improve the quality of life. The expressions of estrogen receptor (ER), progesterone receptor (PR) and human epidermal growth factor receptor-2 (HER-2) present signiifcant differences between primary and metastatic breast cancer. However, these differences may affect the selection of MBC patients for therapeutic strategies and judgment on the prognosis. Hence, the relevant researches on variations of hormone receptors and HER-2 in primary and metastatic breast cancer, discordant causes of ER, PR and HER-2 expression in primary and metastatic lesions and clinical value of biopsy to the metastases are reviewed in the study.

  5. Primary vertebral tumours in children

    Energy Technology Data Exchange (ETDEWEB)

    Kozlowski, K.; Beluffi, G.; Masel, J.; Diard, F.; Ferrari-Ciboldi, F.; Le Dosseur, P.; Labatut, J.

    1984-03-01

    20 cases of primary benign and malignant bone tumours in children were reported. The most common tumours were Ewing's sarcoma, aneurismal bone cyst, benign osteoblastoma and osteoid osteoma. Some rare primary bone tumours in children (osteochondroma, chondroblastoma 6F, primary lymphoma of bone and neurofibromatosis with unusual cervical spinal changes) were also reported. The authors believe that radiographic findings together with clinical history and clinical examination may yield a high percentage of accurate diagnoses. Although microscopy is essential in the final diagnosis, the microscopic report should be also accepted with caution.

  6. Gastric obstruction secondary to metastatic breast cancer: a case report and literature review

    Directory of Open Access Journals (Sweden)

    Hussain Tasadooq

    2012-08-01

    Full Text Available Abstract Introduction Gastrointestinal tract soft tissues metastasis is a well-known occurrence with invasive lobular breast cancer subtypes. Gastric involvement is more common, with reports of both diffuse and localized involvements. Usually, a gastric localized involvement presents as wall thickening with an appearance similar to that of a gastrointestinal stromal tumour; rarely does a localized metastatic deposit grow aggressively to present as a large tumour causing obstructive symptoms. Our case highlights one such unusual presentation in a patient presenting with non-specific gastrointestinal symptoms. To the best of our knowledge, there have been no previous reports on a similar presentation occurring from a localized metastasis. Case presentation A 65-year-old Caucasian woman awaiting an outpatient oral gastroduodenoscopy for symptoms of intermittent vomiting, epigastric pains and weight loss of six weeks’ duration presented acutely with symptoms of haematemesis and abdominal distension. An initial contrast-enhanced computed tomography scan showed a grossly dilated stomach with a locally advanced stenosing tumour mass at the pylorus. Our patient had a history of left mastectomy and axillary clearance followed by adjuvant endocrine therapy for an oestrogen receptor- and progesterone receptor-positive, grade 2, invasive lobular breast cancer. The oral gastroduodenoscopy confirmed the computed tomography findings; biopsies of the pyloric mass on immunohistochemistry stains were strongly positive for pancytokeratin and gross cystic disease fluid proteins, consistent with an invasive lobular breast cancer metastasis. She received a palliative gastrojejunal bypass and her adjuvant endocrine treatment was switched over to exemestane. Conclusion Our case highlights the aggressive behaviour of a localized gastric metastasis that is unusual and unexpected. Gastrointestinal symptomatology can be non-specific and, at times, non-diagnostic on

  7. Breast MRI in clinically and mammographically occult breast cancer presenting with an axillary metastasis: a systematic review

    OpenAIRE

    Bresser, J; De Vos, B.; van der Ent, F.; Hulsewé, K.

    2010-01-01

    Abstract Background Axillary metastatic lymphadenopathy with no primary tumour identified in the breast on physical examination, mammography or ultrasound is referred to as occult breast cancer. The goal of this systematic review is to give an overview of the value and additional considerations of using breast MRI in occult breast cancer. Methods The databases of Pubmed, Embase, CINAHL and the Cochrane library were searched for studies addressing th...

  8. Health care costs and utilization of a large insured female population with advanced or metastatic breast cancer by receipt of HER2-targeted agents

    Directory of Open Access Journals (Sweden)

    Meyer N

    2015-04-01

    Full Text Available Nicole Meyer,1 Yanni Hao,2 Pamela Landsman-Blumberg,1 William Johnson,1 Paul Juneau,3 Jaqueline Willemann Rogerio2 1Truven Health Analytics, Cambridge, MA, USA; 2Novartis Pharmaceuticals, East Hanover, NJ, USA; 3Truven Health Analytics, Washington, DC, USA Background: This retrospective administrative claims study of women diagnosed with advanced or metastatic breast cancer compared health care costs by receipt of HER2-targeted agents and by disease stage and age group among patients using HER2-targeted agents. Methods: Women aged ≥18 years and diagnosed with stage III or IV breast cancer were selected from the 2008–2012 Truven Health MarketScan® databases (Truven Health Analytics Inc., Cambridge, MA, USA databases using ICD-9-CM (International Classification of Diseases, 9th Revision, Clinical Modification codes for nondiagnostic medical claims corresponding to breast cancer and local or distant metastases (earliest diagnosis of stage III or stage IV metastasis was designated as the index date. The 12 months prior to the index date were defined as the pre-index period. The post-index period was variable in length, beginning on the index date and continuing through the end of enrolment, inpatient death, or December 31, 2012, whichever occurred first. Receipt of HER2-targeted agents was defined as at least one claim for trastuzumab or lapatinib in the pre-index or post-index period. The study cohorts were women using or not using HER2-targeted agents, women with stage III or IV breast cancer using HER2-targeted agents, and women using HER2-targeted agents and aged 18–44 years, 45–64 years, or 65+ years at index. Health care costs and utilization were calculated on a per patient per month basis for all-cause and breast cancer-related services by place of service. Generalized linear models were used to estimate total all-cause and breast cancer-related costs. Results: A total of 30,660 eligible women met the study selection criteria, 14

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

    Energy Technology Data Exchange (ETDEWEB)

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

    2009-07-01

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

  10. The Heidelberg classification of renal cell tumours

    NARCIS (Netherlands)

    Kovacs, G; Akhtar, M; Beckwith, BJ; Bugert, P; Cooper, CS; Delahunt, B; Eble, JN; Fleming, S; Ljungberg, B; Medeiros, LJ; Moch, H; Reuter, VE; Ritz, E; Roos, G; Schmidt, D; Srigley, [No Value; Storkel, S; VandenBerg, E; Zbar, B

    1997-01-01

    This paper presents the conclusions of a workshop entitled 'Impact of Molecular Genetics on the Classification of Renal Cell Tumours', which was held in Heidelberg in October 1996, The focus on 'renal cell tumours' excludes any discussion of Wilms' tumour and its variants, or of tumours metastatic t

  11. Soft tissue tumours: imaging strategy

    Energy Technology Data Exchange (ETDEWEB)

    Brisse, Herve J. [Institute Curie, Department of Radiology, Paris (France); Orbach, Daniel [Institute Curie, Department of Paediatric Oncology, Paris (France); Klijanienko, Jerzy [Institute Curie, Department of Pathology, Paris (France)

    2010-06-15

    Vascular tumours and malformations, fibrous and fibrohistiocytic tumours and pseudotumours are the most common benign soft-tissue masses observed in children, and can be treated conservatively. Rhabdomyosarcomas are the most frequent malignant tumours, accounting for about half of soft tissue sarcomas. A child referred for a soft-tissue mass should ideally be managed by a multidisciplinary team and primary excision should be proscribed until a definite diagnosis has been established. Clinical examination, conventional radiography and US with Doppler represent the first-line examinations and are sometimes sufficient to make a diagnosis. In all other situations, MRI is mandatory to establish the aggressiveness and extension of the tumour. This technique provides the relevant data to guide the decision regarding tissue sampling. (orig.)

  12. Advances in breast cancer molecular genetics%乳腺癌分子遗传学研究进展

    Institute of Scientific and Technical Information of China (English)

    孟旭莉

    2010-01-01

    乳腺癌易感基因的研究对有乳腺癌家族史的个体进行早诊和预防、阐明散发性乳腺癌发病机制、早诊、判断药物敏感性和预后、鉴别诊断良恶性疾病等均有重要意义.BRCA1和BRCA2是乳腺癌主要易感基因.其他易感基因诸如TP53能增加BRCA1、BRCA2的乳腺癌患病风险.%The study on susceptibility genes play an important role in early diagnosis and prevention for the individuals with family history of breast carcinoma,elucidation of pathologic mechanism of sporadic breast carcinoma,early diagnosis and adjudging prognosis,research on drug sensitivity,differential diagnosis of benign and malignant disease,etc.Two major susceptibility genes for breast cancer,BRCA1 and BRCA2,are identified,respectively.Other tumor susceptibility genes such as TP53 are known to increase breast cancer risk of BRCA1 and BRCA2.

  13. CEF is superior to CMF for tumours with TOP2A aberrations

    DEFF Research Database (Denmark)

    Gunnarsdóttir, Katrín A; Jensen, Maj-Britt; Zahrieh, David;

    2010-01-01

    The aim of this study was to examine TOP2A gene copy number changes as a means to identify groups of breast cancer patients with superior benefit from treatment with anthracyclines. Tumour tissue was retrospectively collected and successfully analysed for TOP2A in 773 of 980 Danish patients...

  14. Molecular subtypes of breast cancer and amplification of topoisomerase II alpha : predictive role in dose intensive adjuvant chemotherapy

    NARCIS (Netherlands)

    Hannemann, J.; Kristel, P.; van Tinteren, H.; Bontenbal, M.; van Hoesel, Q. G. C. M.; Smit, W. M.; Nooij, M. A.; Voest, E. E.; van der Wall, E.; Hupperets, P.; de Vries, E. G. E.; Rodenhuis, S.; van de Vijver, M. J.

    2006-01-01

    Benefit from chemotherapy treatment in breast cancer patients is determined by the molecular make-up of the tumour. In a retrospective analysis, we determined the molecular subtypes of breast cancer originally defined by expression microarrays by immunohistochemistry in tumours of patients who took

  15. MRI characteristics of midbrain tumours

    Energy Technology Data Exchange (ETDEWEB)

    Sun, B. [Chinese Academy of Medical Science, Beijing (China). Neurosurgical Inst.]|[Department of Neuroradiology, Beijing Tiantan Hospital (China); Wang, C.C.; Wang, J. [Chinese Academy of Medical Science, Beijing (China). Neurosurgical Inst.

    1999-03-01

    We diagnosed 60 cases of midbrain tumours by MRI between 1993 to 1997. There were 39 males and 21 females, aged 2-64 years, mean 25.6 years. We found 38 patients with true intramedullary midbrain tumours, 11 predominantly in the tectum, 20 in the tegmentum and 7 with a downward extension to the pons; there were 7 within the cerebral aqueduct. There were 22 patients with infiltrating midbrain tumours extending from adjacent structures, 11 cases each from the thalamus and pineal region. All patients received surgical treatment. Gross total resection was achieved in 42 cases, subtotal (> 75 %) resection in 18. Pathological diagnoses included 16 low-grade and 15 high-grade astrocytomas; 5 oligodendroastrocytomas; 2 ependymomas; 11 glioblastomas; and 11 pineal parenchymal or germ-cell tumours. Midbrain tumours are a heterogeneous group of neoplasms, with wide variation in clinical and MRI features, related to the site and type of tumour. MRI not only allows precise analysis of their growth pattern, but also can lead to a correct preoperative diagnosis in the majority of cases. (orig.) (orig.) With 3 figs., 3 tabs., 19 refs.

  16. Tumour markers in gastrointestinal cancer

    Energy Technology Data Exchange (ETDEWEB)

    Lamerz, R.

    1988-02-01

    For non-endocrine gastrointestinal tumours the following tumour markers are of clinical interest: For esophageal cancer CEA (sensitivity, s: 40-60%) and SCC (squamous cell carcinoma antigen, x: 20-50%); for gastric cancer CEA (s: 30-40%) as well as CA 19-9 (s: 30-40%) because of complementary results (additive s: 50-60); for hepatocellular cancer AFP (first choice, s: 70-90%; second choice CA 19-9, s: 50-70%); for cholangiocellular cancer CA 19-9 (s: 40-70%); for secondary liver cancer in general CEA; for biliary tract cancer CA 19-9 (s: 40-70%) as well as for excretory pancreatic cancer (s: 70-90%); for colorectal cancer CEA (s: 40-70%) as a first choice marker, and CA 19-9 (s: 20-60%) as a second choice marker, and for anal cancer SCC. The frequency of tumour marker determinations depends on follow-up care recommendations for different tumour diseases (e.g. 1-3 monthly during the 1st and 2nd postoperative year, following chemotherapy courses, on change of therapy, on restaging and at unclear alteration of the clinical state). Tumour markers are only valuable adjuncts to the medical care of tumour patients and therefore useless as solitary findings or on missing therapeutic consequence.

  17. Genome remodelling in a basal-like breast cancer metastasis and xenograft.

    Science.gov (United States)

    Ding, Li; Ellis, Matthew J; Li, Shunqiang; Larson, David E; Chen, Ken; Wallis, John W; Harris, Christopher C; McLellan, Michael D; Fulton, Robert S; Fulton, Lucinda L; Abbott, Rachel M; Hoog, Jeremy; Dooling, David J; Koboldt, Daniel C; Schmidt, Heather; Kalicki, Joelle; Zhang, Qunyuan; Chen, Lei; Lin, Ling; Wendl, Michael C; McMichael, Joshua F; Magrini, Vincent J; Cook, Lisa; McGrath, Sean D; Vickery, Tammi L; Appelbaum, Elizabeth; Deschryver, Katherine; Davies, Sherri; Guintoli, Therese; Lin, Li; Crowder, Robert; Tao, Yu; Snider, Jacqueline E; Smith, Scott M; Dukes, Adam F; Sanderson, Gabriel E; Pohl, Craig S; Delehaunty, Kim D; Fronick, Catrina C; Pape, Kimberley A; Reed, Jerry S; Robinson, Jody S; Hodges, Jennifer S; Schierding, William; Dees, Nathan D; Shen, Dong; Locke, Devin P; Wiechert, Madeline E; Eldred, James M; Peck, Josh B; Oberkfell, Benjamin J; Lolofie, Justin T; Du, Feiyu; Hawkins, Amy E; O'Laughlin, Michelle D; Bernard, Kelly E; Cunningham, Mark; Elliott, Glendoria; Mason, Mark D; Thompson, Dominic M; Ivanovich, Jennifer L; Goodfellow, Paul J; Perou, Charles M; Weinstock, George M; Aft, Rebecca; Watson, Mark; Ley, Timothy J; Wilson, Richard K; Mardis, Elaine R

    2010-04-15

    Massively parallel DNA sequencing technologies provide an unprecedented ability to screen entire genomes for genetic changes associated with tumour progression. Here we describe the genomic analyses of four DNA samples from an African-American patient with basal-like breast cancer: peripheral blood, the primary tumour, a brain metastasis and a xenograft derived from the primary tumour. The metastasis contained two de novo mutations and a large deletion not present in the primary tumour, and was significantly enriched for 20 shared mutations. The xenograft retained all primary tumour mutations and displayed a mutation enrichment pattern that resembled the metastasis. Two overlapping large deletions, encompassing CTNNA1, were present in all three tumour samples. The differential mutation frequencies and structural variation patterns in metastasis and xenograft compared with the primary tumour indicate that secondary tumours may arise from a minority of cells within the primary tumour.

  18. Extrarenal rhabdoid tumours outside the central nervous system in infancy

    Energy Technology Data Exchange (ETDEWEB)

    Garces-Inigo, Enrique F. [Great Ormond Street Hospital for Children, Department of Radiology, London (United Kingdom); Complejo Hospitalario Universitario de Albacete, Radiology Department, Hermanos Falco, Albacete (Spain); Leung, Rebecca; McHugh, Kieran [Great Ormond Street Hospital for Children, Department of Radiology, London (United Kingdom); Sebire, Neil J. [Great Ormond Street Hospital for Children, Department of Histopathology, London (United Kingdom)

    2009-08-15

    Malignant rhabdoid tumours (RT) are increasingly recognized in young children, probably as a consequence of advances in accurate histological diagnosis rather than a true increase in frequency. Although typically presenting as renal tumours in infancy, extrarenal tumours outside the central nervous system (CNS) in children less than 12 months of age are now well recognized, but previous literature on their imaging features is very limited. To demonstrate the imaging features of extrarenal RTs outside the CNS. A retrospective database review was made from 1989 to 2007 of patients diagnosed with extrarenal RT in infancy, i.e. below 12 months of age. There were nine patients (six boys and three girls). The age at presentation varied from 1 to 11 months (average 6 months). Tumours were located in the thorax/mediastinum (n=3), liver (n=3), neck (n=1), shoulder (n=1) and axilla (n=1). The imaging modalities used included US (n=8), CT (n=7) and MRI (n=6). Bone scan was positive in one patient, while metastases at the time of diagnosis occurred in four patients. On MRI the tumours tended to show nonspecific hypointensity on T1-W images and heterogeneous hyperintensity on T2-W images, with heterogeneous enhancement. This is the largest radiological series of extrarenal RTs outside the CNS in infancy. In our series no imaging features were found specific to the diagnosis. A tendency towards large size and mediastinal/paravertebral location were noted. A hypodense solid component on CT and a heterogeneous hyperintensity on T2-W MR images suggest that this tumour should be considered in the routine differential diagnosis of soft-tissue tumours in infancy, in addition to rhabdomyosarcoma. (orig.)

  19. Socioeconomic disparity in survival after breast cancer in ireland: observational study.

    Directory of Open Access Journals (Sweden)

    Paul M Walsh

    Full Text Available We evaluated the relationship between breast cancer survival and deprivation using data from the Irish National Cancer Registry. Cause-specific survival was compared between five area-based socioeconomic deprivation strata using Cox regression. Patient and tumour characteristics and treatment were compared using modified Poisson regression with robust variance estimation. Based on 21356 patients diagnosed 1999-2008, age-standardized five-year survival averaged 80% in the least deprived and 75% in the most deprived stratum. Age-adjusted mortality risk was 33% higher in the most deprived group (hazard ratio 1.33, 95% CI 1.21-1.45, P<0.001. The most deprived groups were more likely to present with advanced stage, high grade or hormone receptor-negative cancer, symptomatically, or with significant comorbidity, and to be smokers or unmarried, and less likely to have breast-conserving surgery. Cox modelling suggested that the available data on patient, tumour and treatment factors could account for only about half of the survival disparity (adjusted hazard ratio 1.18, 95% CI 0.97-1.43, P = 0.093. Survival disparity did not diminish over time, compared with the period 1994-1998. Persistent survival disparities among Irish breast cancer patients suggest unequal use of or access to services and highlight the need for further research to understand and remove the behavioural or other barriers involved.

  20. Sialyl-Tn vaccine induces antibody-mediated tumour protection in a relevant murine model

    DEFF Research Database (Denmark)

    Julien, S; Picco, G; Sewell, R;

    2009-01-01

    be carried on various glycoproteins. One such glycoprotein MUC1 is expressed by the vast majority of breast carcinomas. Both STn and MUC1 have been considered as targets for immunotherapy of breast cancer patients. Here we used different immunogens to target STn in an MUC1 transgenic mouse model of tumour......Changes in the composition of glycans added to glycoproteins and glycolipids are characteristic of the change to malignancy. Sialyl-Tn (STn) is expressed by 25-30% of breast carcinomas but its expression on normal tissue is highly restricted. Sialyl-Tn is an O-linked disaccharide that can...

  1. La quimioterapia neoadyuvante en el tratamiento del cáncer de mama localmente avanzado Neoadyuvant chemotherapy in the treatment of locally advanced breast cancer

    Directory of Open Access Journals (Sweden)

    Mayer Zaharia

    2013-03-01

    Full Text Available Al inicio del tratamiento del cáncer, se pensaba que este se diseminaba por continuidad, lo cual originó que las primeras estrategias para el manejo de cáncer de mama localmente avanzado fueran altamente agresivas, además de mutilantes. Con los avances en el conocimiento de la biología de la enfermedad, se generaron importantes cambios en el manejo de esta neoplasia. Surgió entonces como alternativa terapéutica la quimioterapia neoadyuvante, que es aquella que se administra previamente al tratamiento quirúrgico. Descrita inicialmente por la escuela de Milán, ha probado ser una mejor alternativa que el tratamiento quirúrgico solo, que la quimioterapia adyuvante (o postquirúrgica y que la radioterapia sola o en combinación con las técnicas señaladas previamente. Dentro de las ventajas de la quimioterapia neoadyuvante se encuentran el incremento de la tasa de las cirugías conservadoras de mama y la disminución de la tasa de recaída ipsilateral. Facilita además el control y seguimiento de la enfermedad. Sin embargo, la principal desventaja es que no puede modificar algunos factores pronósticos de la enfermedad como la relación tumor mama, enfermedad multicéntrica, las microcalcificaciones dispersas y la coexistencia de procesos médicos que contraindiquen la radioterapia. Actualmente, la quimioterapia neoadyuvante es la base del manejo del cáncer de mama localmente avanzado y está recomendada para garantizar una evolución más conservadora en el manejo de esta enfermedadIn the first stages of cancer treatment, it was believed that it spreaded by continuity, so the first strategies to treat locally advanced breast cancer were highly aggressive, as well as mutilating. A deeper knowledge of the biology of cancer later resulted in important changes in its treatment, such as the use of neoadyuvant chemotherapy, administered prior to surgical treatment, as an alternative therapy. Initially described by the University of Milan

  2. Tumour length is an independent prognostic factor of esophageal squamous cell carcinomas

    Institute of Scientific and Technical Information of China (English)

    WU Ning; PANG Lie-wen; CHEN Zhi-ming; MA Qin-yun; CHEN Gang

    2012-01-01

    Background The latest version of the American Joint Committee on Cancer (AJCC) TNM staging system has not comprehensively evaluated the impact of tumour length on survival in patients with esophageal squamous cell carcinoma.Our study explored the relationship between tumour length and clinicopathological characteristics as well as long-term survival.Methods All 202 cases of esophageal resections done from January 1,2004 to December 31,2008 in Huashan Hospital,Fudan University were reviewed and followed up.Results Patients with tumour length >3 cm were related to more advanced tumour stage (X2=55.9,P <0.001),more metastatic lymph nodes (X2=14.6,P <0.001),increased metastatic lymph node ratio (x2=16.1,P <0.001) and worse overall TNM stage (X2=48.1,P <0.001).Univariate and multivariate analyses indicated that tumour length was a significant prognostic risk factor (95% CI 0.235-0.947,P=0.035).Subgroup analyses disclosed that tumour length was a valuable prognostic predictor in patients with lower T stage,absence of metastatic lymph nodes and lower TNM stage.Conclusions Esophageal tumour length is a predictive factor for long-term survival especially for lower tumour stage,absence of metastatic lymph nodes and lower TNM stage patients.Tumour length should be incorporated in the staging system as an important grouping factor for better prognostic evaluation.

  3. Combined liver transplantation plus imatinib for unresectable metastases of gastrointestinal stromal tumours.

    Science.gov (United States)

    Serralta, Alfonso S; Sanjuan, Fernando R; Moya, Angel H; Orbis, Francisco C; López-Andújar, Rafael; Pareja, Eugenia I; Vila, Juan C; Rayón, Miguel; Juan, Manuel B; Mir, José P

    2004-11-01

    Therapeutic options for treating unresectable hepatic metastases of leiomyosarcomas were scarce until a few years ago. Recent advances in the study of the biology of intestinal tumours have radically changed our knowledge of their pathogenesis. Many of the tumours previously considered as leiomyosarcomas are now identified as gastrointestinal stromal tumours (GISTs). The introduction of imatinib (an antineoplasic drug that specifically acts on the pathogenesis of these tumours) has shown promising results in patients with advanced GISTs. We present three patients with the initial diagnosis of unresectable hepatic metastases of leiomyosarcomas. They received liver transplants. All three had tumour recurrences after transplantation. Histological re-evaluation identified a stromal origin of the tumours, and the patients were treated with imatinib therapy (400 mg/day). Recurrence occurred in all patients after a mean of 38.3 months, but imatinib treatment achieved control of the tumours. The current survival times with the combination of transplantation and imatinib are 92, 48 and 46 months for the three patients. This series is small and inconclusive, but imatinib treatment showed promising results. The treatment options for patients with unresectable metastases of GISTs must be defined, as in these three patients liver transplantation achieved a disease-free status but all had tumour recurrences before starting the imatinib treatment.

  4. [Skin-sparing mastectomy: an alternative to conventional mastectomy in breast cancer].

    Science.gov (United States)

    Ramos Boyero, Manuel

    2008-10-01

    Women who require or desire mastectomy for breast cancer one option should be immediate breast reconstruction. Skin-sparing mastectomy (SSM) describes the surgery that maximises breast skin and infra- mammary fold preservation, significantly improves the symmetry and natural appearance and a more satisfied patient. In multiple studies, SSM seems to be oncologically safe in patients undergoing mastectomy for invasive T1-T2 tumours, multicentric tumours, ductal carcinoma in situ or risk-reduction. However, the technique should be avoided in patients with inflammatory breast cancer or in those with extensive tumour involvement of the skin. SSM with nipple areola complex preservation appears to be oncologically safe, providing that the tumour is not close to the nipple and the retro-areolar tissue is free of tumour. Though adjuvant radiotherapy is not an absolute contraindication to SSM, it should be used with caution since it decreases the final cosmetic result.

  5. An ER activity profile including ER, PR, Bcl-2 and IGF-IR may have potential as selection criterion for letrozole or tamoxifen treatment of patients with advanced breast cancer

    DEFF Research Database (Denmark)

    Henriksen, Katrine L; Rasmussen, Birgitte B; Lykkesfeldt, Anne E

    2009-01-01

    microarrays from formalin fixed paraffin embedded primary tumor material from a subgroup of patients (9.4%), who have participated in the international, randomized, phase III clinical trial PO25 comparing letrozole with tamoxifen in 907 patients with advanced breast cancer. The expression levels of ER...

  6. 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

    Directory of Open Access Journals (Sweden)

    V Raina

    2011-01-01

    Full Text Available 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 1995 to December 2004. We analyzed the response to NACT, disease-free survival (DFS, and overall survival (OS. Results: Patients with stages IIIA, IIIB, and IIIC were included. LABC comprised of 26.24% (609 patients of new patients. One hundred and twenty-eight (31.1% patients received NACT. Median age was 48 years and estrogen receptor was positive in 64%. Chemotherapy protocol was an FEC (5-Fluorouracil, Epirubicin, Cyclophosphamide regimen in the following doses: Cyclophosphamide 600 mg/m2, 5-FU 600 mg/m2, and Epirubicin 75 mg/m2 given every three weeks, six doses, followed by modified radical mastectomy (MRM and locoregional radiotherapy. The overall response rate (complete response (CR + partial response (PR was 84.4%, clinical CR (cCR was 13.3% and pathological CR (pCR was 7.8%. Median DFS and OS were 33 and 101 months, respectively. The disease-free survival (DFS and overall survival (OS at five years were 41 and 58%, respectively. Conclusions: This study analyzes the outcome in patients who received NACT, in the largest number of LABC patients from a single center in India, and our results are comparable to the results reported from other centers.

  7. Matrix stiffness drives Epithelial-Mesenchymal Transition and tumour metastasis through a TWIST1-G3BP2 mechanotransduction pathway

    OpenAIRE

    Wei, SC; Fattet, L; Tsai, JH; Guo, Y.; Pai, VH; Majeski, HE; Chen, AC; Sah, RL; Taylor, SS; ENGLER, AJ; Yang, J.

    2015-01-01

    © 2015 Macmillan Publishers Limited. Matrix stiffness potently regulates cellular behaviour in various biological contexts. In breast tumours, the presence of dense clusters of collagen fibrils indicates increased matrix stiffness and correlates with poor survival. It is unclear how mechanical inputs are transduced into transcriptional outputs to drive tumour progression. Here we report that TWIST1 is an essential mechanomediator that promotes epithelial-mesenchymal transition (EMT) in respon...

  8. WILMS’ TUMOUR IN YOUNG ADULT

    Directory of Open Access Journals (Sweden)

    Senthilvel Arumugam

    2016-08-01

    Full Text Available Wilms’ tumour also called as nephroblastoma is a malignant renal neoplasm of childhood that arises from remnant of immature kidney. About 80% of Wilms’ tumour cases occur before age 5 with a median age of 3.5 years. But adult Wilms’ tumour can occur at any age from 16 to 70 years, the median age in young adult is around 24. CASE REPORT A 16-year-old girl came with history of mass right abdomen, which she noticed for 1 week duration; no urinary symptoms. Her recent blood pressure was 140/90 mmHg. Per abdomen a 10 x 9 cm mass palpable in the right lumbar region, surface smooth, firmto-hard in consistency, non-tender, well defined, no bruit. Urine routine examination was normal; urine culture was sterile; renal and liver function tests were within normal limits; Sr. calcium 9.5 mg/dL. CT abdomen plain and contrast showed a 10 x 9 cm heterodense lesion equivocal with renal cell carcinoma and angiomyolipoma. MR angiogram was done. It showed well-defined encapsulated heterointense mass of size 12 x 8 x 7cm, IVC and bilateral renal vein normal. Since findings were inconclusive, we did a CT-guided biopsy and report came as feature positive for small round cell tumour. Hence, proceeded with right radical nephrectomy. The final histopathology report came as Wilms’ tumour spindle cell variant. Margins clear and ureter not involved. She was then started on adjuvant chemotherapy Inj. Vincristine 2 mg weekly for 27 weeks. She is on regular followup now. CONCLUSION Wilms’ tumour should be considered in a patient who presents with a renal mass with or without loin pain, haematuria especially in young adults. Every attempt should be made to differentiate it from renal cell carcinoma. The outcome for adult Wilms’ tumour is steadily improving with current multimodality treatment approach.

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

    Energy Technology Data Exchange (ETDEWEB)

    Svanberg, K.; Wang, I. [Lund Univ. Hospital (Sweden). Lund Medical Laser Centre]|[Lund Univ. Hospital (Sweden). Dept. of Oncology; Colleen, S. [Lund Univ. Hospital (Sweden). Lund Medical Laser Centre]|[Lund Univ. Hospital (Sweden). Dept. of Urology; Idvall, I. [Lund Univ. Hospital (Sweden). Lund Medical Laser Centre]|[Lund Univ. Hospital (Sweden). Dept. of Pathology; Ingvar, C. [Lund Univ. Hospital (Sweden). Lund Medical Laser Centre]|[Lund Univ. Hospital (Sweden). Dept. of Surgery; Rydell, R. [Lund Univ. Hospital (Sweden). Lund Medical Laser Centre]|[Lund Univ. Hospital (Sweden). Dept. of Oto-Rhino-Laryngology; Jocham, D. [Luebeck Univ. (Germany). Abt. fuer Urologie; Diddens, H. [Luebeck Univ. (Germany). Medizinisches Laser Zentrum; Bown, S.; Gregory, G. [National Medical Laser Centre, Dept. of Surgery, Rayne Inst., London (United Kingdom); Montan, S. [Spectraphos AB, Ideon, Lund (Sweden); Andersson-Engels, S.; Svanberg, S. [Lund Univ. Hospital (Sweden). Lund Medical Laser Centre]|[Lund Inst. of Technology (Sweden). Dept. of Physics

    1998-01-01

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

  10. Research advance in microRNAs and breast cancer.%MicroRNA与乳腺癌研究进展

    Institute of Scientific and Technical Information of China (English)

    卞国奉; 陈爱军

    2012-01-01

    MicroRNAs (miRNAs) are a major class of small endogenous RNA molecules that post-transcription-ally regulate gene expression. Several miRNAs have been proved to be related to human cancers, including breast cancer. The loss of several tumor suppressor miRNAs and the overexpression of certain oncogenic miRNAs have been observed in breast cancers. Here we describe the relationship of miRNA with the tumorigenesis and metastasis of breast cancer.%MicroRNAs (miRNAs)是一种内源性的小RNA分子,在基因的转录后能调节其表达.许多MicroRNAs被证实与各种肿瘤相关,包括乳腺癌.某些抑癌性MicroRNAs的缺失和致癌性MicroRNAs的过表达已经在许多乳腺癌中被发现.本文就MicroRNAs与乳腺癌发生发展之间的联系以及与一些乳腺癌相关的MicroRNA及其作用作一综述.

  11. Vincristine, doxorubicin and mitomycin (VAM) in patients with advanced breast cancer previously treated with cyclophosphamide, methotrexate and fluorouracil (CMF). A clinical trial of the Piedmont Oncology Association (POA).

    Science.gov (United States)

    Shipp, S K; Muss, H B; Westrick, M A; Cooper, M R; Jackson, D V; Richards, F C; White, D R; Stuart, J J; Christian, R M; Ramseur, W

    1983-01-01

    Thirty-six evaluable patients with advanced breast cancer who had failed prior CMF therapy [15 (42%) as adjuvant treatment and 21 (58%) for advanced disease] were treated with a combination of vincristine, doxorubicin, and mitomycin (VAM). There was one CR and 10 PR, giving a response rate of 31% (P, 95% confidence interval, 15%-47%). Response was not significantly related to age, performance status, disease-free interval, dominant site of disease, number of sites of disease, or estrogen receptor status. The median duration of response was 5 months for patients attaining CR or PR and 4.6 months for patients with stable disease. The median survival for patients with CR or PR of 7.9 months was not better than for those with stable disease (8.0 months), but both groups had significantly longer survival than those with initial progression. Patients who received VAM after failing adjuvant CMF had a 53% response rate (8 of 15), as against a 14% response rate (3 of 21) in those failing CMF for advanced disease (P less than 0.05). In spite of this difference, the survival distributions for these two groups were not significantly different. Myelosuppression was moderate and no cardiac toxicity was seen. The addition of mitomycin to vincristine and doxorubicin in previously treated patients does not appear to improve the results obtained with vincristine and doxorubicin alone.

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

    Science.gov (United States)

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

    2012-04-01

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

  13. Surface impedance based microwave imaging method for breast cancer screening: contrast-enhanced scenario.

    Science.gov (United States)

    Güren, Onan; Çayören, Mehmet; Ergene, Lale Tükenmez; Akduman, Ibrahim

    2014-10-01

    A new microwave imaging method that uses microwave contrast agents is presented for the detection and localization of breast tumours. The method is based on the reconstruction of breast surface impedance through a measured scattered field. The surface impedance modelling allows for representing the electrical properties of the breasts in terms of impedance boundary conditions, which enable us to map the inner structure of the breasts into surface impedance functions. Later a simple quantitative method is proposed to screen breasts against malignant tumours where the detection procedure is based on weighted cross correlations among impedance functions. Numerical results demonstrate that the method is capable of detecting small malignancies and provides reasonable localization.

  14. Education and training for advanced practice: Principles of course design and assessment applied to a 'stereotactic needle core biopsy of the breast' module

    Energy Technology Data Exchange (ETDEWEB)

    Dixon, Anne-Marie [Division of Radiography, University of Bradford, Bradford BD5 0BB (United Kingdom)]. E-mail: a.m.dixon@bradford.ac.uk

    2006-05-15

    In order to realise the promise of the NHS Plan, radiographers are extending their practice to encompass tasks previously undertaken by radiologists and advancing their practice by taking responsibility for clinical decision-making and autonomous membership of multidisciplinary healthcare teams. In partnership with clinical service providers Higher Education Institutes are devising programmes of study to support such professional development. This article reviews the design of a 20 credit post-graduate (M level) module in stereotactic needle core biopsy of the breast. Particular consideration is given to underpinning educational principles of course design and assessment and how these are applied in order that teaching, learning and assessment have academic rigour and clinical competence of successful students is assured.

  15. In situ aromatase expression in primary tumor is associated with estrogen receptor expression but is not predictive of response to endocrine therapy in advanced breast cancer

    DEFF Research Database (Denmark)

    Lykkesfeldt, Anne E; Henriksen, Katrine L; Rasmussen, Birgitte B;

    2009-01-01

    whether in situ carcinoma cell aromatization is the primary source of estrogen production for tumor growth and whether the aromatase expression is predictive of response to endocrine therapy. Due to methodological difficulties in the determination of the aromatase protein, COX-2, an enzyme involved...... of advanced breast cancer. Semi-quantitative immunohistochemical (IHC) analysis was performed for ER, PR, COX-2 and aromatase using Tissue Microarrays (TMAs). Aromatase was also analyzed using whole sections (WS). Kappa analysis was applied to compare association of protein expression levels. Univariate...... TMAs. Expression of COX-2 and aromatase did not predict response to endocrine therapy. Aromatase in combination with high PR expression may select letrozole treated patients with a longer TTP. CONCLUSION: TMAs are not suitable for IHC analysis of in situ aromatase expression and we did not find COX-2...

  16. FDG PET and other imaging modalities in the primary diagnosis of suspicious breast lesions

    Energy Technology Data Exchange (ETDEWEB)

    Scheidhauer, K.; Seemann, M.D. [Department of Nuclear Medicine, Klinikum rechts der Isar der Technischen Universitaet Muenchen, Ismaninger Strasse 22, 81675, Munich (Germany); Walter, C. [Department of Diagnostic Radiology, Krankenhaus der Barmherzigen Brueder, Trier (Germany)

    2004-06-01

    Mammography is the primary imaging modality for screening of breast cancer and evaluation of breast lesions (T staging). Ultrasonography is an adjunctive tool for mammographically suspicious lesions, in patients with mastopathy and as guidance for reliable histological diagnosis with percutaneous biopsy. Dynamic enhanced magnetic resonance mammography (MRM) has a high sensitivity for the detection of breast cancer, but also a high false positive diagnosis rate. In the literature, MRM is reported to have a sensitivity of 86-96%, a specificity of 64-91%, an accuracy of 79-93%, a positive predictive value (PPV) of 77-92% and a negative predictive value (NPV) of 75-94%. In unclarified cases, metabolic imaging using fluorine-18 fluorodeoxyglucose positron emission tomography (FDG PET) can be performed. In the literature, FDG PET is reported to have a sensitivity of 64-96%, a specificity of 73-100%, an accuracy of 70-97%, a PPV of 81-100% and an NPV of 52-89%. Furthermore, PET or PET/CT using FDG has an important role in the assessment of N and M staging of breast cancer, the prediction of tumour response in patients with locally advanced breast cancer receiving neoadjuvant chemotherapy, and the differentiation of scar and cancer recurrence. Other functional radionuclide-based diagnostic tools, such as scintimammography with sestamibi, peptide scintigraphy or immunoscintigraphy, have a lower accuracy than FDG PET and, therefore, are appropriate only for exceptional indications. (orig.)

  17. Proteomic classification of breast cancer.

    LENUS (Irish Health Repository)

    Kamel, Dalia

    2012-11-01

    Being a significant health problem that affects patients in various age groups, breast cancer has been extensively studied to date. Recently, molecular breast cancer classification has advanced significantly with the availability of genomic profiling technologies. Proteomic technologies have also advanced from traditional protein assays including enzyme-linked immunosorbent assay, immunoblotting and immunohistochemistry to more comprehensive approaches including mass spectrometry and reverse phase protein lysate arrays (RPPA). The purpose of this manuscript is to review the current protein markers that influence breast cancer prediction and prognosis and to focus on novel advances in proteomic classification of breast cancer.

  18. Long-term outcome after neoadjuvant radiochemotherapy in locally advanced noninflammatory breast cancer and predictive factors for a pathologic complete remission. Results of a multivariate analysis

    Energy Technology Data Exchange (ETDEWEB)

    Matuschek, C.; Boelke, E.; Roth, S.L. [Duesseldorf Univ. (Germany). Dept. of Radiation Oncology] [and others

    2012-09-15

    An earlier published series of neoadjuvant radiochemotherapy (NRT-CHX) in locally advanced noninflammatory breast cancer (LABC) has now been updated with a follow-up of more than 15 years. Long-term outcome data and predictive factors for pathologic complete response (pCR) were analyzed. Patients and methods: During 1991-1998, 315 LABC patients (cT1-cT4/cN0-N1) were treated with NRT-CHX. Preoperative radiotherapy (RT) consisted of external beam radiation therapy (EBRT) of 50 Gy (5 x 2 Gy/week) to the breast and the supra-/infraclavicular lymph nodes combined with an electron boost in 214 cases afterwards or - in case of breast conservation - a 10-Gy interstitial boost with {sup 192}Ir afterloading before EBRT. Chemotherapy was administered prior to RT in 192 patients, and concomitantly in 113; 10 patients received no chemotherapy. The update of all follow-up ended in November 2011. Age, tumor grade, nodal status, hormone receptor status, simultaneous vs. sequential CHX, and the time interval between end of RT and surgery were examined in multivariate terms with pCR and overall survival as end point. Results: The total pCR rate after neoadjuvant RT-CHX reached 29.2%, with LABC breast conservation becoming possible in 50.8% of cases. In initially node-positive cases (cN+), a complete nodal response (pN0) after NRT-CHX was observed in 56% (89/159). The multivariate analysis revealed that a longer time interval to surgery increased the probability for a pCR (HR 1.17 [95% CI 1.05-1.31], p < 0.01). However, in large tumors (T3-T4) a significantly reduced pCR rate (HR 0.89 [95% CI 0.80-0.99], p = 0.03) was obtained. Importantly, pCR was the strongest prognostic factor for long-term survival (HR 0.28 [95% CI 0.19-0.56], p < 0.001). Conclusion: pCR identifies patients with a significantly better prognosis for long-term survival. However, a long time interval to surgery (> 2 months) increases the probability of pCR after NRT-CHX. (orig.)

  19. Current problems in the first-line treatment of metastatic breast cancer: focus on the role of docetaxel

    Directory of Open Access Journals (Sweden)

    Filippo Montemurro

    2010-09-01

    Full Text Available Metastatic breast cancer is a very heterogeneous disease, both from a clinical and a biological point of view. Despite being still incurable, the expanding therapeutic repertoire has determined a progressive increase in median survival. We describe the clinical course of a 67-year-old woman with a locally advanced, hormone-receptor positive breast cancer with synchronous liver metastases. Single-agent docetaxel at the dose of 100 mg/m2 for 8 cycles determined a pathological complete remission in the breast and a near complete remission of liver metastases. After more than 4 years from diagnosis, the patient is alive and without signs of tumour progression. Based on this clinical case, we discuss management issues like the choice of the initial treatment, the use of monochemotherapy vs polychemotherapy, the worth of surgery of the primary tumour in patients with stage IV disease, and the issue of maintenance endocrine therapy. Furthermore, we reviewed the pivotal role of docetaxel in the management of advanced breast cancer. Whether monochemotherapy or polychemotherapy is felt to be an adequate choice in the clinical practice, docetaxel qualifies as one of the most active and manageable agents. Single agent activity ranging from 20-48% in terms of response rate has been reported in several clinical trials in patients treated in various clinical settings. Docetaxel-based combinations with other cytotoxic agents have become established in the first line treatment both in patients with anthracycline-resistant and anthracycline-sensitive metastatic breast cancer. Finally, docetaxel has been shown to be an optimal companion drug for biologically targeted agents like trastuzumab or bevacizumab, resulting in further treatment options.

  20. Analysis of BRCA1 involvement in breast cancer in Indian women

    Indian Academy of Sciences (India)

    P H Pestonjamasp; I Mittra

    2000-03-01

    The involvement of the familial breast-ovarian cancer gene (BRCA1) in the molecular pathogenesis of breast cancer among Indian women is unknown. We have used a set of microsatellite polymorphisms to examine the frequency of allele loss at the BRCA1 region on chromosome 17q21, in a panel of 80 human breast tumours. Tumour and blood leukocyte/normal tissue DNA from a series of 80 patients with primary breast cancer was screened by PCR-amplified microsatellite length polymorphisms to detect deletions at three polymorphic BRCA1 loci. PCR-allelotype was valuable in examining allele losses from archival and small tumour samples. Loss of alleles at BRCA1 in the patient set, confirmed a noteworthy role of this gene in the molecular pathogenesis of breast cancer and was in accordance with its well-documented tumour suppressive function.

  1. The value of diagnosis method for breast small tumour tissue quantitative analysis of acoustic palpation%声触诊组织定量分析法对乳腺小肿块诊断价值

    Institute of Scientific and Technical Information of China (English)

    刘琳; 吴蓉; 吴晶心; 姚明华

    2014-01-01

    目的:探讨声触诊组织定量分析技术(V T Q)在女性乳腺小肿块(≤10m m)良恶性鉴别诊断中的应用价值。方法:回顾性分析于2012年6月至2013年12月间收集的128例女性乳腺小肿块超声检测结果,与病理结果进行对比分析,所有患者均行常规超声及超声弹性成像检查,分别测量肿块的剪切波(SWV)值。以术后病理结果为诊断标准,做出受试曲线(ROC)并计算曲线下面积(AUC)。结果:良性肿块的剪切波平均值为(2.18±0.72)m/s,恶性肿块的剪切波平均值为(3.96±0.86)m/s,两者比较有显著统计学差异。根据良恶性肿块的剪切波平均值,以敏感性为纵坐标,(1-特异性)为横坐标,制作受试曲线(R O C)并计算曲线下面积(A U C)为0.836,当截断值为3.09m/s时,诊断恶性病变的敏感性为87.9%,特异性为89.9%,准确率为91.5%。结论:声触诊组织定量分析技术(VTQ)能够定量评价肿块的硬度,为乳腺小肿块的良恶性鉴别诊断提供重要价值。%Objective:Analysis on the technology of virtual touch tissue quantitative (VTQ) in breast lumps (≤10mm) application value in differential diagnosis of benign and malignant. Methods:A retrospective analysis of 128 cases of breast lumps from 2012 June to 2013 December were collected,and the results were compared with the pathological results,all patients underwent conventional ultrasound and ultrasound elasticity imaging,shear wave mass were measured (SWV) value. The postoperative pathological results as diagnostic criteria,make the curve (ROC) and the calculation of the area under the curve (AUC). Results:Shear wave benign mass averaged (2.18±0.72) m/s,the average value of shear wave and malignant tumors (3.96±0.86) m/s,there is signiifcant difference. According to the average value of shear wave in benign and malignant tumors,the sensitivity for the vertical axis,(1-specific) as

  2. Immediate Breast Reconstruction with a Subpectorally Placed Silicone Prosthesis: Rheumatological, psychological and clinical aspects

    NARCIS (Netherlands)

    C.M.E. Contant

    2003-01-01

    markdownabstract__Abstract__ Breast cancer is the most frequently diagnosed solid tumour in women in the western world. In the Netherlands, breast cancer affects about 1.2 per 1000 women a year. At present about 10% of all Dutch women develop breast cancer in the course of their life, of whom appro

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

    DEFF Research Database (Denmark)

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

    2008-01-01

    The Danish Breast Cancer Cooperative Group's register containing data from about 75 000 patients undergoing surgery for primary invasive breast cancer from 1978-2006 has been examined for classical pathological variables. During that period the diagnostic approach of malignant breast tumours...

  4. IRAK1 is a therapeutic target that drives breast cancer metastasis and resistance to paclitaxel

    DEFF Research Database (Denmark)

    Wee, Zhen Ning; Yatim, Siti Maryam J M; Kohlbauer, Vera K

    2015-01-01

    Metastatic tumour recurrence due to failed treatments remains a major challenge of breast cancer clinical management. Here we report that interleukin-1 receptor-associated kinase 1 (IRAK1) is overexpressed in a subset of breast cancers, in particular triple-negative breast cancer (TNBC), where...

  5. Preoperative shunts in thalamic tumours.

    Directory of Open Access Journals (Sweden)

    Goel A

    2000-10-01

    Full Text Available Thirty one patients with thalamic glioma underwent a pre-tumour resection shunt surgery. The procedure was uneventful in 23 patients with relief from symptoms of increased intracranial pressure. Eight patients worsened after the procedure. The level of sensorium worsened from excessively drowsy state to unconsciousness in seven patients. Three patients developed hemiparesis, 4 developed paresis of extra-ocular muscles and altered pupillary reflexes, and 1 developed incontinence of urine and persistent vomiting. Alteration in the delicately balanced intracranial pressure and movements in the tumour and vital adjacent brain areas could be the probable cause of the worsening in the neurological state in these 8 patients. On the basis of these observations and on review of literature, it is postulated that the ventricular dilatation following an obstruction in the path of the cerebrospinal fluid flow by a tumour could be a natural defense phenomenon of the brain.

  6. 低分子肝素联合化疗治疗晚期乳腺癌%Low molecular heparin combined chemotherapy in advanced breast cancer

    Institute of Scientific and Technical Information of China (English)

    赵丽丽; 刘力新; 张秀娟

    2011-01-01

    Objective: To observe the effect of low molecular heparin in combined with chemotherapy on blood clots markers D dimmers and fibrinogen in advanced breast cancer. Methods: Total of 42 patients with metastatic breast cancer were randomly divided into two groups, patients in group A received pachtaxel plus cisplatin; patients in group B received regimen TP combined with low molecular heparin 5000U subcutaneously injected ql2 hours per day, for 5 days. Group B: low molecular heparin and TP scheme chemotherapy group, on the base of drug in group A combined with low molecular heparin 5000U subcutaneous injection 12 hours 1 times, for five days. Results: There was no significant difference in low molecular heparin group D-dimers before and after chemotherapy. Level of fibrinogen after chemotherapy was significantly lower than the level before chemotherapy( P 0. 05 ). There was on significant differences in adverse reactions between 2 groups. Conclusion: The application of low molecular heparin combined chemotherapy can improve high pour - point state in advanced breast cancer without obvious adverse reactions.%目的:观察低分子肝素联合化疗对晚期乳腺癌的疗效及对血栓标志物(D二聚体、纤维蛋白原)的影响.方法:42例晚期乳腺癌患者随机分成两组.A组:TP化疗组,应用紫杉醇135mg/m2第1天静脉滴注,顺铂70 mg/m2第2天静脉滴注.B组:低分子肝素联合TP方案化疗组,在A组用药的基础上加用低分子肝素5000U 皮下注射 12小时1次,共用5天.结果:低分子肝素组D二聚体化疗前后无明显变化(P>0.05),纤维蛋白原化疗后明显低于化疗前水平(P0.05).低分子肝素组治疗的不良反应较单纯化疗组统计学差异无显著性(P>0.05).结论:应用低分子肝素联合化疗能改善晚期乳腺癌高凝状态,无明显不良反应.

  7. Awareness of breast cancer risk factors and practice of breast self examination among high school students in Turkey

    OpenAIRE

    Çetinkaya Aynur; Özmen Dilek; Karayurt Özgül

    2008-01-01

    Abstract Background Young breast cancer patients have a lower rate of survival than old breast cancer patients due to being diagnosed at advanced stages. Breast self-examination makes women more "breast aware", which in turn may lead to an earlier diagnosis of breast cancer. The purpose of this study was to investigate knowledge and practice of breast self-examination and to determine knowledge of risk factors for breast cancer among high school students. Methods This is a descriptive and cro...

  8. Germ cell tumours of the ovary. A clinical study of 15 cases.

    Science.gov (United States)

    Friedman, M; Browde, S; Nissenbaum, M M

    1984-04-14

    Our experience with germ cell tumours of the ovary is reviewed. Over the last 10 years, 15 cases, representing 6,4% of all our referred patients with malignant ovarian tumours, have been analysed. The type of tumour, histological appearances, stage, treatment and results of treatment are presented. The tumour most commonly seen was the dysgerminoma, comprising 60% of all cases (9 patients). Multimodal treatment generally consisted of surgery and radiotherapy for dysgerminoma with the addition of chemotherapy for the non-dysgerminomas. Survival depends on the stage and histological appearances of the tumour. Patients in whom the disease is at advanced stages have a poor prognosis, irrespective of histological features. A general review of this subject is also given.

  9. Tumour endothelial cells in high metastatic tumours promote metastasis via epigenetic dysregulation of biglycan

    Science.gov (United States)

    Maishi, Nako; Ohba, Yusuke; Akiyama, Kosuke; Ohga, Noritaka; Hamada, Jun-ichi; Nagao-Kitamoto, Hiroko; Alam, Mohammad Towfik; Yamamoto, Kazuyuki; Kawamoto, Taisuke; Inoue, Nobuo; Taketomi, Akinobu; Shindoh, Masanobu; Hida, Yasuhiro; Hida, Kyoko

    2016-01-01

    Tumour blood vessels are gateways for distant metastasis. Recent studies have revealed that tumour endothelial cells (TECs) demonstrate distinct phenotypes from their normal counterparts. We have demonstrated that features of TECs are different depending on tumour malignancy, suggesting that TECs communicate with surrounding tumour cells. However, the contribution of TECs to metastasis has not been elucidated. Here, we show that TECs actively promote tumour metastasis through a bidirectional interaction between tumour cells and TECs. Co-implantation of TECs isolated from highly metastatic tumours accelerated lung metastases of low metastatic tumours. Biglycan, a small leucine-rich repeat proteoglycan secreted from TECs, activated tumour cell migration via nuclear factor-κB and extracellular signal–regulated kinase 1/2. Biglycan expression was upregulated by DNA demethylation in TECs. Collectively, our results demonstrate that TECs are altered in their microenvironment and, in turn, instigate tumour cells to metastasize, which is a novel mechanism for tumour metastasis. PMID:27295191

  10. Wilms tumour: prognostic factors, staging, therapy and late effects

    Energy Technology Data Exchange (ETDEWEB)

    Kaste, Sue C. [St. Jude Children' s Research Hospital, Department of Radiological Sciences, Memphis, TN (United States); Dome, Jeffrey S. [St. Jude Children' s Research Hospital, Department of Oncology, Memphis, TN (United States); Babyn, Paul S. [Hospital for Sick Children, Department of Radiology, Toronto (Canada); Graf, Norbert M. [University Hospital of the Saarland, Clinic for Pediatric Oncology and Hematology, Homburg (Germany); Grundy, Paul [University of Alberta, Division of Pediatric Hematology, Oncology and Palliative Care, and Northern Alberta Children' s Cancer Program, Edmonton (Canada); Godzinski, Jan [Mother and Child Institute, Department of Oncological Surgery for Children and Adolescents, Warsaw (Poland); Levitt, Gill A. [Great Ormond Street Hospital for Sick Children NHS Trust, Paediatric Oncology, London (United Kingdom); Jenkinson, Helen [Birmingham Children' s Hospital NHS Trust, Oncology Department, Birmingham (United Kingdom)

    2008-01-15

    Wilms tumour is the most common malignant renal tumour in children. Dramatic improvements in survival have occurred as the result of advances in anaesthetic and surgical management, irradiation and chemotherapy. Current therapies are based on trials and studies primarily conducted by large multi-institutional cooperatives including the Societe Internationale d'Oncologie Pediatrique (SIOP) and the Children's Oncology Group (COG). The primary goals are to treat patients according to well-defined risk groups in order to achieve the highest cure rates, to decrease the frequency and intensity of acute and late toxicity and to minimize the cost of therapy. The SIOP trials and studies largely focus on the issue of preoperative therapy, whereas the COG trials and studies start with primary surgery. This paper reviews prognostic factors and staging systems for Wilms tumour and its current treatment with surgery and chemotherapy. Surgery remains a crucial part of treatment for nephroblastoma, providing local primary tumour control and adequate staging and possibly controlling the metastatic spread and central vascular extension of the disease. Partial nephrectomy, when technically feasible, seems reasonable not only in those with bilateral disease but also in those with unilateral disease where the patient has urological disorders or syndromes predisposing to malignancy. Partial nephrectomy, however, is frequently not sufficient for an anaplastic variant of tumour. The late effects for Wilms tumour and its treatment are also reviewed. The treatment of Wilms tumour has been a success story, and currently in excess of 80% of children diagnosed with Wilms tumour can look forward to long-term survival, with less than 20% experiencing serious morbidity at 20 years from diagnosis. The late complications are a consequence of the type and intensity of treatment required, which in turn reflects the nature and extent of the original tumour. Continual international trial

  11. Loco-regional control after neo-adjuvant chemotherapy and conservative treatment for locally advanced breast cancer patients.

    Science.gov (United States)

    Levy, Antonin; Borget, Isabelle; Bahri, Manel; Arnedos, Monica; Rivin, Eleonor; Vielh, Philippe; Balleyguier, Corinne; Rimareix, Françoise; Bourgier, Céline

    2014-01-01

    Breast-conserving treatment (BCT) has been validated for breast cancer patients receiving adjuvant chemotherapy. Our objective was to evaluate the difference in loco-regional recurrence (LRR) rates between BCT and mastectomy in patients receiving radiation therapy after neo-adjuvant chemotherapy (NCT). A retrospective data base was used to identify all patients with breast cancer undergoing NCT from 2002 to 2007. Patients with initial metastatic disease were excluded from this analysis. LRR was compared between those undergoing BCT and mastectomy. Individual variables associated with LRR were evaluated. Two hundred eighty-four patients were included, 111 (39%) underwent BCT and 173 (61%) mastectomy. Almost all patients (99%) in both groups received postoperative radiation. Pathologic complete response was seen in 37 patients, of which 28 underwent BCT (p loco-regional control rate was 91% (95% CI: 86-94%). The 10-year LRR rate was similar in the BCT group (9.2% [95% CI: 4.9-16.7%]) and in the mastectomy group (10.7% [95% CI: 5.9-15.2%]; p = 0.8). Ten-year overall survival (OS) rates (63% [95% CI: 46-79%] in the BCT group; 60% [95% CI: 47-73%] in the mastectomy group, p = 0.8) were not statistically different between the two patient populations. Multivariate analysis showed that AJCC stage ≥ III (HR: 2.6; 95% CI: 1.2-5.8; p = 0.02), negative PR (HR: 6; 95% CI: 1.2-30.6, p = 0.03), and number of positive lymph nodes ≥3 (HR: 2.5; 95% CI: 1.1-5.9; p = 0.03) were independent predictors of LRR. Ten-year OS was similar in the BCT and in the mastectomy group (p = 0.1). The rate of LRR was low and did not significantly differ between the BCT and the mastectomy group after NCT. Randomized trials assessing whether mastectomy can be safely omitted in selected breast cancer patients (nonstage III tumors or those which do not require adjuvant hormone suppression) which respond to NCT are required.

  12. 卵巢切除联合依西美坦治疗绝经前激素受体阳性晚期难治性乳腺癌%Bilateral oophorectomy combined with exemestane treating advanced refractory breast cancer

    Institute of Scientific and Technical Information of China (English)

    Xinhong Wu; Yaojun Feng; Juan Xu; Yiping Gong; Biao Ma

    2011-01-01

    Objective: Taking tamoxifen orally is the main endocrine therapy