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

Valentina Silvestri, 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. Domchek, Timothy R. Rebbeck, Susan J. Ramus, Robert L. Nussbaum, Olufunmilayo I. Olopade, Johanna Rantala, Sook Yee Yoon, Maria A. CaligoLaura Spugnesi, Anders Bojesen, Inge Sokilde Pedersen, Mads Thomassen, Uffe Birk Jensen, Amanda Ewart Toland, Leigha Senter, Irene L. Andrulis, Gord Glendon, Peter J. Hulick, Evgeny N. Imyanitov, 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 Pinto, Marco Montagna, Laura Matricardi, Adalgeir Arason, Oskar Th Johannsson, Rosa B. Barkardottir, Anna Jakubowska, Jan Lubinski, Angel Izquierdo, Miguel Angel Pujana, Judith Balmaña, Orland Diez, Gabriella Ivady, Janos Papp, Edith Olah, Ava Kwong, Heli Nevanlinna, Kristiina Aittomäki, Pedro Perez Segura, Trinidad Caldes, Tom Van Maerken, Bruce Poppe, Kathleen B M Claes, Claudine Isaacs, Camille Elan, Christine Lasset, Dominique Stoppa-Lyonnet, Laure Barjhoux, Muriel Belotti, Alfons Meindl, Andrea Gehrig, Christian Sutter, Christoph Engel, 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 V O 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, Laura Ottini

Research output: Contribution to journalArticlepeer-review


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 × 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 × 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.

Original languageEnglish
Article number15
JournalBreast Cancer Research
Issue number1
Publication statusPublished - Feb 9 2016


  • BRCA1/2
  • Genotype-phenotype correlations
  • Histologic grade
  • Male breast cancer
  • Pathology

ASJC Scopus subject areas

  • Cancer Research
  • Oncology


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