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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RESEARCH PRODUCT

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

Silvestri V. Barrowdale C Dmulligan A. M.Author Demail Neuhausen S. L. Eemail Author Fox S. Femail Author Karlan B. Y. Gemail Author H Mitchell G.Author Iemail H James P.Author Iemail Thull D. L. Jemail Author Zorn K. K. Jemail Author Carter N. J. Kemail Author Nathanson K. L. Lemail Author Domchek S. M. Lemail Author Rebbeck T. R. Memail Author Ramus S. J. Nemail Author Nussbaum R. L. Oemail Author Olopade O. I. Pemail Author Rantala J. Qemail Author Yoon R S. -Y.Author Semail Caligo M. A. Temail Author Spugnesi L. Temail Author Bojesen A. Uemail Author Pedersen I. S. Vemail Author Thomassen M. Wemail Author Jensen U. B. Xemail Author Toland A. E. Yemail Author Senter L. Zemail Author D Andrulis I. L. Aa Author Abemail Glendon G. Aaemail Author Hulick P. J. Acemail Author Imyanitov E. N. Ademail Author Greene M. H. Aeemail Author Mai P. L. Aeemail Author Singer C. F. Afemail Author Rappaport-fuerhauser C. Afemail Author Kramer G. Agemail Author Vijai J. Ahemail Author Offit K. Ahemail Author Robson M. Aiemail Author Lincoln A. Ahemail Author Jacobs L. Ahemail Author Machackova E. Ajemail Author Foretova L. Akemail Author Navratilova M. Ajemail Author Vasickova P. Ajemail Author Couch Al F. J.Author Amemail Hallberg E. Amemail Author Ruddy K. J. Anemail Author Sharma P. Aoemail Author Kim S. -W. Apemail Author Teixeira Aq M. R.Author Aremail Pinto P. Aqemail Author Montagna M. Asemail Author Matricardi L. Asemail Author Arason A. Atemail Author Johannsson O. T. Auemail Author Barkardottir R. B. Atemail Author Jakubowska A. Avemail Author Lubinski J. Avemail Author Izquierdo A. Awemail Author Pujana M. A. Axemail Author Balmaña J. Ayemail Author Diez O. Azemail Author Ivady G. Baemail Author Papp J. Bbemail Author Olah E. Bbemail Author Kwong A. Bc Author Bdemail Nevanlinna H. Beemail Author Aittomäki K. Bfemail Author Segura Perez P. Bgemail Author Caldes T. Bhemail Author Maerken Van T. Biemail Author Poppe B. Biemail Author Claes K. B. M. Biemail Author Isaacs C. Bjemail Author Elan C. Bkemail Author Lasset C. Bl Author Bmemail Stoppa-lyonnet D. Bk Author Bnemail Barjhoux L. Boemail Author Belotti M. Bkemail Author Meindl A. Bpemail Author Gehrig A. Bqemail Author Sutter C. Bremail Author Engel C. Bsemail Author Niederacher D. Btemail Author Steinemann D. Buemail Author Hahnen E. Bvemail Author Kast K. Bwemail Author Arnold N. Bxemail Author Varon-mateeva R. Byemail Author Wand D. Bzemail Author Godwin A. K. Caemail Author Evans D. G. Cbemail Author Frost D. Bemail Author Perkins J. Bemail Author Adlard J. Ccemail Author Izatt L. Cdemail Author Platte R. Ceemail Author Eeles R. Cfemail Author Ellis S. Bemail Author Hamann U. Cfemail Author Garber J. Cgemail Author Fostira F. Chemail Author Fountzilas G. Ciemail Author Pasini B. Cj Author Ckemail Giannini G. Aemail Author Rizzolo P. Aemail Author Russo A. Clemail Author Cortesi L. Cmemail Author Laura Papi L. Cnemail Author Varesco L. Coemail Author Palli D. Cpemail Author Zanna I. Cpemail Author Savarese A. Cqemail Author Radice P. Cremail Author Manoukian S. Csemail Author Peissel B. Csemail Author Barile M. Ctemail Author Bonanni B. Ctemail Author Viel A. Cuemail Author Pensotti V. Cv Author Cwemail Tommasi S. Cxemail Author Peterlongo P. Cvemail Author Weitzel J. N. Cyemail Author Osorio A. Cz Author Daemail Benitez J. Da Db Author Dcemail Mcguffog L. Bemail Author Healey S. Ddemail Author Gerdes A. -M. Deemail Author Ejlertsen B. Dfemail Author Hansen T. V. O. Dgemail Author Steele L. Eemail Author Ding Y. C. Eemail Author Tung N. Dhemail Author Janavicius R. Diemail Author Goldgar D. E. Djemail Author Buys S. S. Dkemail Author Daly M. B. Dlemail Author Bane A. Dmemail Author Terry M. B. Dnemail Author John E. M. Doemail Author Southey M. Dpemail Author Easton D. F. Bemail Author Chenevix-trench G. Ddemail Author Antoniou A. C. Bemail Author Ottini L Papi

subject

Male 0301 basic medicine Genotype-phenotype correlation Pathology genotype-phenotype correlations endocrine system diseases Settore MED/06 - Oncologia Medica FEATURES male breast cancer Genotype-phenotype correlations Logistic regression Histologic grade 610 Medical sciences Medicine Breast cancer 0302 clinical medicine Epidemiology Medicine and Health Sciences Pathology polycyclic compounds skin and connective tissue diseases POPULATION RISK education.field_of_study BRCA1 Protein Men Single Nucleotide Middle Aged 3. Good health GRADE 030220 oncology & carcinogenesis Male breast cancer oncology Female Breast Neoplasm Research Article Human Adult medicine.medical_specialty CARCINOMA Genotype–phenotype correlations 3122 Cancers Population 610 Breast Neoplasms BRCA1/2; genotype-phenotype correlations; histologic grade; male breast cancer; pathology; cancer research; oncology Male breast cancer BRCA1 BRCA2 Polymorphism Single Nucleotide Càncer de mama Breast Neoplasms Male 03 medical and health sciences Breast cancer SDG 3 - Good Health and Well-being BRCA1/2 Journal Article Carcinoma medicine Humans Genetic Predisposition to Disease Polymorphism education Aged Neoplasm Staging BRCA2 Protein business.industry Odds ratio histologic grade medicine.disease Confidence interval Male breast cancer 030104 developmental biology ddc:161 Homes Mutation cancer research pathology BRCA1/2; Genotype-phenotype correlations; Histologic grade; Male breast cancer; Pathology; Adult; Aged; BRCA1 Protein; BRCA2 Protein; Breast Neoplasms; Breast Neoplasms Male; Female; Genetic Predisposition to Disease; Humans; Male; Middle Aged; Mutation; Neoplasm Staging; Polymorphism Single Nucleotide; Oncology; Cancer Research business

description

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. Electronic supplementary material The online version of this article (doi:10.1186/s13058-016-0671-y) contains supplementary material, which is available to authorized users.

year	journal	country	edition	language
2016-02-09

10.1186/s13058-016-0671-y https://pure.eur.nl/en/publications/72d8fbc3-3840-448a-9cf6-92802e804ea0