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Male breast cancer in BRCA1 and BRCA2 mutation carriers: pathology data from the Consortium of Investigators of Modifiers of BRCA1/2

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Abstract
Background: BRCA1 and, more commonly, BRCA2 mutations are associated with increased risk of male breast cancer (MBC). However, only a paucity of data exists on the pathology of breast cancers (BCs) in men with BRCA1/2 mutations. Using the largest available dataset, we determined whether MBCs arising in BRCA1/2 mutation carriers display specific pathologic features and whether these features differ from those of BRCA1/2 female BCs (FBCs). Methods: We characterised the pathologic features of 419 BRCA1/2 MBCs and, using logistic regression analysis, contrasted those with data from 9675 BRCA1/2 FBCs and with population-based data from 6351 MBCs in the Surveillance, Epidemiology, and End Results (SEER) database. Results: Among BRCA2 MBCs, grade significantly decreased with increasing age at diagnosis (P = 0.005). Compared with BRCA2 FBCs, BRCA2 MBCs were of significantly higher stage (P for trend = 2 x 10(-5)) and higher grade (P for trend = 0.005) and were more likely to be oestrogen receptor-positive [odds ratio (OR) 10.59; 95 % confidence interval (CI) 5.15-21.80] and progesterone receptor-positive (OR 5.04; 95 % CI 3.17-8.04). With the exception of grade, similar patterns of associations emerged when we compared BRCA1 MBCs and FBCs. BRCA2 MBCs also presented with higher grade than MBCs from the SEER database (P for trend = 4 x 10(-12)). Conclusions: On the basis of the largest series analysed to date, our results show that BRCA1/2 MBCs display distinct pathologic characteristics compared with BRCA1/2 FBCs, and we identified a specific BRCA2-associated MBC phenotype characterised by a variable suggesting greater biological aggressiveness (i.e., high histologic grade). These findings could lead to the development of gender-specific risk prediction models and guide clinical strategies appropriate for MBC management.
Keywords
POPULATION, GRADE, RISK, BRCA1/2, Pathology, Male breast cancer, Genotype-phenotype correlations, Histologic grade, CARCINOMA, FEATURES

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MLA
Silvestri, Valentina, et al. “Male Breast Cancer in BRCA1 and BRCA2 Mutation Carriers: Pathology Data from the Consortium of Investigators of Modifiers of BRCA1/2.” BREAST CANCER RESEARCH, vol. 18, 2016, doi:10.1186/s13058-016-0671-y.
APA
Silvestri, V., Barrowdale, D., Mulligan, A. M., Neuhausen, S. L., Fox, S., Karlan, B. Y., … Ottini, L. (2016). Male breast cancer in BRCA1 and BRCA2 mutation carriers: pathology data from the Consortium of Investigators of Modifiers of BRCA1/2. BREAST CANCER RESEARCH, 18. https://doi.org/10.1186/s13058-016-0671-y
Chicago author-date
Silvestri, Valentina, Daniel Barrowdale, Anna Marie Mulligan, Susan L Neuhausen, Stephen Fox, Beth Y Karlan, Gillian Mitchell, et al. 2016. “Male Breast Cancer in BRCA1 and BRCA2 Mutation Carriers: Pathology Data from the Consortium of Investigators of Modifiers of BRCA1/2.” BREAST CANCER RESEARCH 18. https://doi.org/10.1186/s13058-016-0671-y.
Chicago author-date (all authors)
Silvestri, Valentina, Daniel Barrowdale, Anna Marie Mulligan, Susan L Neuhausen, Stephen Fox, Beth Y Karlan, Gillian Mitchell, Paul James, Darcy L Thull, Kristin K Zorn, Natalie J Carter, Katherine L Nathanson, Susan M Dornchek, Timothy R Rebbeck, Susan J Ramus, Robert L Nussbaum, Olufunrnilayo I Olopade, Johanna Rantala, Sook-Yee Yoon, Maria A Caligo, Laura Spugnesi, Anders Bojesen, Inge Sokilde Pedersen, Muds Thomassen, Uffe Birk Jensen, Amanda Ewart Toland, Leigha Senter, Irene L Andrulis, Gord Glendon, Peter J Hulick, Evgeny N Irnyanitov, Mark H Greene, Phuong L Mai, Christian F Singer, Christine Rappaport-Fuerhauser, Gero Kramer, Joseph Vijai, Kenneth Offit, Mark Robson, Anne Lincoln, Lauren Jacobs, Eva Machackova, Lenka Foretova, Marie Navratilova, Petra Vasickova, Fergus J Couch, Emily Hallberg, Kathryn J Ruddy, Priyanka Sharma, Sung-Won Kim, Manuel R Teixeira, Pedro Pinte, Marco Montagna, Laura Matricardi, Adalgeir Arason, Oskar Th Johannsson, Rosa B Barkardottir, Anna Jakubowska, Jan Lubinski, Angel Izquierdo, Miguel Angel Pujana, Judith Balmana, Orland Diez, Gabriella Ivady, Janos Papp, Edith Olah, Ava Kwong, Heli Nevanlinna, Kristiina Aittomaki, Pedro Perez Segura, Trinidad Caldes, Tom Van Maerken, Bruce Poppe, Kathleen Claes, Claudine Isaacs, Camille Elan, Christine Lasset, Dominique Stoppa-Lyonnet, Laure Barjhoux, Muriel Belotti, Alfons Meindl, Andrea Gehrig, Christian Sutter, Christoph Enger, Dieter Niederacher, Doris Steinemann, Eric Hahnen, Karin Kast, Norbert Arnold, Raymonda Varon-Mateeva, Dorothea Wand, Andrew K Godwin, D Gareth Evans, Debra Frost, Jo Perkins, Julian Adlard, Louise Izatt, Radka Platte, Ros Eeles, Steve Ellis, Ute Hamann, Judy Garber, Florentia Fostira, George Fountzilas, Barbara Pasini, Giuseppe Giannini, Piera Rizzolo, Antonio Russo, Laura Cortesi, Laura Papi, Liliana Varesco, Domenico Palli, Ines Zanna, Antonella Savarese, Paolo Radice, Siranoush Manoukian, Bernard Peissel, Monica Barile, Bernardo Bonanni, Alessandra Viel, Valeria Pensotti, Stefania Tommasi, Paolo Peterlongo, Jeffrey N Weitzel, Ana Osorio, Javier Benitez, Lesley McGuffog, Sue Healey, Anne-Marie Gerdes, Bent Ejlertsen, Thomas VO Hansen, Linda Steele, Yuan Chun Ding, Nadine Tung, Ramunas Janavicius, David E Goldgar, Saundra S Buys, Mary B Daly, Anita Bane, Mary Beth Terry, Esther M John, Melissa Southey, Douglas F Easton, Georgia Chenevix-Trench, Antonis C Antoniou, and Laura Ottini. 2016. “Male Breast Cancer in BRCA1 and BRCA2 Mutation Carriers: Pathology Data from the Consortium of Investigators of Modifiers of BRCA1/2.” BREAST CANCER RESEARCH 18. doi:10.1186/s13058-016-0671-y.
Vancouver
1.
Silvestri V, Barrowdale D, Mulligan AM, Neuhausen SL, Fox S, Karlan BY, et al. Male breast cancer in BRCA1 and BRCA2 mutation carriers: pathology data from the Consortium of Investigators of Modifiers of BRCA1/2. BREAST CANCER RESEARCH. 2016;18.
IEEE
[1]
V. Silvestri et al., “Male breast cancer in BRCA1 and BRCA2 mutation carriers: pathology data from the Consortium of Investigators of Modifiers of BRCA1/2,” BREAST CANCER RESEARCH, vol. 18, 2016.
@article{7157963,
  abstract     = {{Background: BRCA1 and, more commonly, BRCA2 mutations are associated with increased risk of male breast cancer (MBC). However, only a paucity of data exists on the pathology of breast cancers (BCs) in men with BRCA1/2 mutations. Using the largest available dataset, we determined whether MBCs arising in BRCA1/2 mutation carriers display specific pathologic features and whether these features differ from those of BRCA1/2 female BCs (FBCs). 
Methods: We characterised the pathologic features of 419 BRCA1/2 MBCs and, using logistic regression analysis, contrasted those with data from 9675 BRCA1/2 FBCs and with population-based data from 6351 MBCs in the Surveillance, Epidemiology, and End Results (SEER) database. 
Results: Among BRCA2 MBCs, grade significantly decreased with increasing age at diagnosis (P = 0.005). Compared with BRCA2 FBCs, BRCA2 MBCs were of significantly higher stage (P for trend = 2 x 10(-5)) and higher grade (P for trend = 0.005) and were more likely to be oestrogen receptor-positive [odds ratio (OR) 10.59; 95 % confidence interval (CI) 5.15-21.80] and progesterone receptor-positive (OR 5.04; 95 % CI 3.17-8.04). With the exception of grade, similar patterns of associations emerged when we compared BRCA1 MBCs and FBCs. BRCA2 MBCs also presented with higher grade than MBCs from the SEER database (P for trend = 4 x 10(-12)). 
Conclusions: On the basis of the largest series analysed to date, our results show that BRCA1/2 MBCs display distinct pathologic characteristics compared with BRCA1/2 FBCs, and we identified a specific BRCA2-associated MBC phenotype characterised by a variable suggesting greater biological aggressiveness (i.e., high histologic grade). These findings could lead to the development of gender-specific risk prediction models and guide clinical strategies appropriate for MBC management.}},
  articleno    = {{15}},
  author       = {{Silvestri, Valentina and Barrowdale, Daniel and Mulligan, Anna Marie and Neuhausen, Susan L and Fox, Stephen and Karlan, Beth Y and Mitchell, Gillian and James, Paul and Thull, Darcy L and Zorn, Kristin K and Carter, Natalie J and Nathanson, Katherine L and Dornchek, Susan M and Rebbeck, Timothy R and Ramus, Susan J and Nussbaum, Robert L and Olopade, Olufunrnilayo I and Rantala, Johanna and Yoon, Sook-Yee and Caligo, Maria A and Spugnesi, Laura and Bojesen, Anders and Pedersen, Inge Sokilde and Thomassen, Muds and Jensen, Uffe Birk and Toland, Amanda Ewart and Senter, Leigha and Andrulis, Irene L and Glendon, Gord and Hulick, Peter J and Irnyanitov, Evgeny N and Greene, Mark H and Mai, Phuong L and Singer, Christian F and Rappaport-Fuerhauser, Christine and Kramer, Gero and Vijai, Joseph and Offit, Kenneth and Robson, Mark and Lincoln, Anne and Jacobs, Lauren and Machackova, Eva and Foretova, Lenka and Navratilova, Marie and Vasickova, Petra and Couch, Fergus J and Hallberg, Emily and Ruddy, Kathryn J and Sharma, Priyanka and Kim, Sung-Won and Teixeira, Manuel R and Pinte, Pedro and Montagna, Marco and Matricardi, Laura and Arason, Adalgeir and Johannsson, Oskar Th and Barkardottir, Rosa B and Jakubowska, Anna and Lubinski, Jan and Izquierdo, Angel and Angel Pujana, Miguel and Balmana, Judith and Diez, Orland and Ivady, Gabriella and Papp, Janos and Olah, Edith and Kwong, Ava and Nevanlinna, Heli and Aittomaki, Kristiina and Perez Segura, Pedro and Caldes, Trinidad and Van Maerken, Tom and Poppe, Bruce and Claes, Kathleen and Isaacs, Claudine and Elan, Camille and Lasset, Christine and Stoppa-Lyonnet, Dominique and Barjhoux, Laure and Belotti, Muriel and Meindl, Alfons and Gehrig, Andrea and Sutter, Christian and Enger, Christoph and Niederacher, Dieter and Steinemann, Doris and Hahnen, Eric and Kast, Karin and Arnold, Norbert and Varon-Mateeva, Raymonda and Wand, Dorothea and Godwin, Andrew K and Evans, D Gareth and Frost, Debra and Perkins, Jo and Adlard, Julian and Izatt, Louise and Platte, Radka and Eeles, Ros and Ellis, Steve and Hamann, Ute and Garber, Judy and Fostira, Florentia and Fountzilas, George and Pasini, Barbara and Giannini, Giuseppe and Rizzolo, Piera and Russo, Antonio and Cortesi, Laura and Papi, Laura and Varesco, Liliana and Palli, Domenico and Zanna, Ines and Savarese, Antonella and Radice, Paolo and Manoukian, Siranoush and Peissel, Bernard and Barile, Monica and Bonanni, Bernardo and Viel, Alessandra and Pensotti, Valeria and Tommasi, Stefania and Peterlongo, Paolo and Weitzel, Jeffrey N and Osorio, Ana and Benitez, Javier and McGuffog, Lesley and Healey, Sue and Gerdes, Anne-Marie and Ejlertsen, Bent and Hansen, Thomas VO and Steele, Linda and Ding, Yuan Chun and Tung, Nadine and Janavicius, Ramunas and Goldgar, David E and Buys, Saundra S and Daly, Mary B and Bane, Anita and Terry, Mary Beth and John, Esther M and Southey, Melissa and Easton, Douglas F and Chenevix-Trench, Georgia and Antoniou, Antonis C and Ottini, Laura}},
  issn         = {{1465-542X}},
  journal      = {{BREAST CANCER RESEARCH}},
  keywords     = {{POPULATION,GRADE,RISK,BRCA1/2,Pathology,Male breast cancer,Genotype-phenotype correlations,Histologic grade,CARCINOMA,FEATURES}},
  language     = {{eng}},
  pages        = {{13}},
  title        = {{Male breast cancer in BRCA1 and BRCA2 mutation carriers: pathology data from the Consortium of Investigators of Modifiers of BRCA1/2}},
  url          = {{http://doi.org/10.1186/s13058-016-0671-y}},
  volume       = {{18}},
  year         = {{2016}},
}

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