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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

2016; BioMed Central; Volume: 18; Issue: 1 Linguagem: Inglês

10.1186/s13058-016-0671-y

1465-542X

Valentina Silvestri, Daniel Barrowdale, Anna Marie Mulligan, Susan L. Neuhausen, Stephen B. Fox, Beth Y. Karlan, Gillian Mitchell, Paul A. 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. Caligo, Laura Spugnesi, Anders Bojesen, Inge Søkilde Pedersen, Mads Thomassen, Uffe Birk Jensen, Amanda E. Toland, Leigha Senter, Irene L. Andrulis, Gord Glendon, Peter J. Hulick, Evgeny N. Imyanitov, Mark H. Greene, L. Phuong, Christian F. Singer, Christine Rappaport, Gero Kramer, Joseph Vijai, Kenneth Offit, Mark E. Robson, Anne Lincoln, Lauren Jacobs, Eva Macháčková, Lenka Foretová, Marie Navrátilová, Petra Vašíčková, Fergus J. Couch, Emily Hallberg, Kathryn J. Ruddy, Priyanka Sharma, Sung‐Won Kim, Manuel R. Teixeira, Pedro Pinto, Marco Montagna, Laura Matricardi, Aðalgeir Arason, Oskar T. Johannsson, Rósa B. Barkardóttir, Anna Jakubowska, Jan Lubiński, À. Izquierdo, Miguel Ángel Pujana, Judith Balmañà, Orland Dı́ez, Gabriella Ivády, J. Papp, Edith Oláh, Ava Kwong, Heli Nevanlinna, Kristiina Aittomäki, Pedro Pérez Segura, Miguel de la Hoya, 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 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, Rosalind A. Eeles, Ian O. Ellis, Ute Hamann, Judy E. 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 Osório, Javier Benı́tez, Lesley McGuffog, Sue Healey, Anne–Marie Gerdes, Bent Ejlertsen, Thomas van Overeem Hansen, Linda Steele, Yuan Chun Ding, Nadine Tung, Ramūnas Janavičius, David E. Goldgar, Saundra S. Buys, Mary B. Daly, Anita Bane, Mary Beth Terry, Esther M. John, Melissa C. Southey, Douglas F. Easton, Georgia Chenevix‐Trench, Antonis C. Antoniou, Laura Ottini,

DNA Repair Mechanisms

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). 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. 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). 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.