Florentia Fostira1, Emmanouil Saloustros2, Paraskevi Apostolou3, Andromahi Vagena3, Despoina Kalfakakou3, Davide Mauri4, Dimitrios Tryfonopoulos5, Vassileios Georgoulias6, Drakoulis Yannoukakos3, Georgios Fountzilas7, Irene Konstantopoulou3. 1. Molecular Diagnostics Laboratory, INRaSTES, National Centre for Scientific Research 'Demokritos', Patriarchou Gregoriou E' & Neapoleos Street, 15310, Athens, Greece. florentia_fostira@hotmail.com. 2. Oncology Unit, General Hospital of Heraklion 'Venizelio-Pananio', Heraklion, Crete, Greece. 3. Molecular Diagnostics Laboratory, INRaSTES, National Centre for Scientific Research 'Demokritos', Patriarchou Gregoriou E' & Neapoleos Street, 15310, Athens, Greece. 4. General Hospital of Lamia, Lamia, Greece. 5. Second Department of Medical Oncology, 'Agios Savvas' Anticancer Hospital, Athens, Greece. 6. Department of Medical Oncology, University Hospital of Heraklion, Heraklion, Greece. 7. Aristotle University of Thessaloniki School of Medicine, Thessaloniki, Greece.
Abstract
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.
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 MBCpatients, 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 MBCpatients are reported here for the first time. CONCLUSIONS: Our findings, using the largest gene panel for MBCpatients so far, indicate that BRCA testing should be the primary concern for MBCpatients. Until sufficient evidence arises from larger studies, multiple-gene panels may be of limited benefit for MBC and their families, at least for MBCpatients of specific descent.
Entities:
Keywords:
BRCA1; BRCA2; Hereditary cancer; Male breast cancer; NGS
Authors: Ksenija Strojnik; Mateja Krajc; Vita Setrajcic Dragos; Vida Stegel; Srdjan Novakovic; Ana Blatnik Journal: Breast Cancer Res Treat Date: 2021-04-23 Impact factor: 4.872