Journal Article

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

Singer, dcEmail Author, D. bzEmail Author, J. ccEmail Author, Wand, M. wEmail Author, daEmail Author, Carter, Ruddy, Chenevix-Trench, A. bqEmail Author, D. btEmail Author, D. buEmail Author, S. csEmail Author, S. bEmail Author, P. crEmail Author, J. cgEmail Author, P. L. aeEmail Author, M. R. aq, D. L. jEmail Author, Engel, aa, P. cvEmail Author, Healey, Pinto, Navratilova, V. cv, S. cxEmail Author, Steele, O. I. pEmail Author, Pasini, Offit, Tommasi, S. fEmail Author, Diez, Arason, Tung, Bojesen, ckEmail Author, Claes, A. avEmail Author, Machackova, Bane, B. Y. gEmail Author, Giannini, A. awEmail Author, Jakubowska, McGuffog, L. tEmail Author, Jacobs, A. atEmail Author, Andrulis I. L. d, S. M. lEmail Author, T. V. O. dgEmail Author, A. cuEmail Author, C. F. afEmail Author, A. uEmail Author, A. ahEmail Author, M. ctEmail Author, Garber, A. clEmail Author, Couch, D. cpEmail Author, D. bk, G. agEmail Author, P. aoEmail Author, A. cqEmail Author, L. zEmail Author, G. ciEmail Author, cwEmail Author, Silvestri, J. ahEmail Author, Ivady, M. ajEmail Author, Kast, Varesco, Russo, M. aiEmail Author, P. ajEmail Author, Peterlongo, Caldes, Zorn, E. bbEmail

2016

Overview

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.

• Publisher: Springer Science and Business Media LLC,BioMed Central,BioMed Central Ltd,Springer Nature B.V
• Subject: 610 Medical sciences Medicine / Adult / Aged / Analysis / Biomedical and Life Sciences / Biomedicine / BRCA1 Protein / BRCA1 Protein - genetics / BRCA1/2 / 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 / BRCA1/2; genotype-phenotype correlations; histologic grade; male breast cancer; pathology; cancer research; oncology / BRCA2 Protein / BRCA2 Protein - genetics / Breast cancer / Breast Neoplasms / Breast Neoplasms - genetics / Breast Neoplasms - pathology / Breast Neoplasms, Male / Breast Neoplasms, Male - genetics / Breast Neoplasms, Male - pathology / Cancer / Cancer Research / Cancers / CARCINOMA / Care and treatment / Complications and side effects / Càncer de mama / ddc:161 / ddc:no / EMBRACE / EMC MM-03-24-01 / EMC MM-03-86-01 / FEATURES / Female / Gene mutations / Genetic aspects / Genetic Predisposition to Disease / Genotype-phenotype correlations / GRADE / Hereditary Breast and Ovarian Cancer Research Group Netherlands (HEBON) / Histologic grade / Homes / Humans / kConFab Investigators / Male / Male breast cancer / Male breast cancer, BRCA1, BRCA2 / Male/genetics / Medicine and Health Sciences / Men / Middle Aged / Mutation / Neoplasm Staging / Oncology / Pathology / Polymorphism / Polymorphism, Single Nucleotide / POPULATION / Research Article / RISK / SDG 3 - Good Health and Well-being / Settore MED/06 - Oncologia Medica / Single Nucleotide / Surgical Oncology