Germline deleterious mutations in genes other than BRCA2 are infrequent in male breast cancer

• Published in: Breast cancer research and treatment 2018-05, Vol.169 (1), p.105-113
• Main Authors: Fostira, Florentia, Saloustros, Emmanouil, Apostolou, Paraskevi, Vagena, Andromahi, Kalfakakou, Despoina, Mauri, Davide, Tryfonopoulos, Dimitrios, Georgoulias, Vassileios, Yannoukakos, Drakoulis, Fountzilas, Georgios, Konstantopoulou, Irene
• Format: Article
• Language: English
• Subjects: Aged; BRCA1 protein; BRCA1 Protein - genetics; BRCA2 protein; BRCA2 Protein - genetics; Breast cancer; Breast Neoplasms, Male - epidemiology; Breast Neoplasms, Male - genetics; Breast Neoplasms, Male - pathology; Cancer genetics; Cancer research; Checkpoint Kinase 2 - genetics; Deoxyribonucleic acid; DNA; Epidemiology; Family medical history; Founder Effect; Gene mutation; Genes; Genetic aspects; Genetic Predisposition to Disease; Genetic Testing; Germ-Line Mutation - genetics; Humans; Loss of Function Mutation - genetics; Male; Males; Medical schools; Medicine; Medicine & Public Health; Mens health; Middle Aged; Mutation; Oncology; Sequence Deletion - genetics
• ISSN: 0167-6806; 1573-7217
• DOI: 10.1007/s10549-018-4661-x

Purpose Male breast cancer (MBC) is a rare cancer entity, with mutations in BRCA1 and BRCA2 genes accounting for ~ 10% of patients. Multiple-gene sequencing has already entered clinical practice for female breast cancer, whereas the performance of panel testing in MBC has not been studied extensively. Therefore, the aim of this study was to evaluate the clinical utility of panel testing for MBC, by the largest gene panel used so far, through investigation of patients deriving from a population with known founder effects. Methods Genomic DNA from one hundred and two Greek MBC patients, unselected for age and family history, was used to prepare libraries which capture the entire coding regions of 94 cancer genes. Results Loss-of-function (LoF) mutations were found in 12.7% of the cases, distributed in six genes: BRCA2, ATM, BRCA1, CHEK2, PMS2, and FANCL. BRCA2 mutations were the most frequent, followed by ATM mutations, accounting for 6.9 and 2%, respectively, while mutations in other genes were detected in single cases. Age at diagnosis or family history was not predictive of mutation status. Beyond mutations in established breast cancer predisposing genes, LoF mutations in PMS2 and FANCL among MBC patients are reported here for the first time. Conclusions Our findings, using the largest gene panel for MBC patients so far, indicate that BRCA testing should be the primary concern for MBC patients. Until sufficient evidence arises from larger studies, multiple-gene panels may be of limited benefit for MBC and their families, at least for MBC patients of specific descent.