Male Breast Cancer: From Molecular Genetics to Clinical Management

SIMPLE SUMMARY: Male breast cancer (MBC) is a rare disease. Genetic factors predispose to male breast cancer. Germline and/or genetic and/or epigenetic alterations at the somatic level identify a subset of male breast cancer that could differ from female breast cancer (FBC). Cancer genetic counseling should be included in the work-up of male breast cancer to identify the possible genetic origin of the tumor and to offer patients and their at-risk family members adequate management. ABSTRACT: MBC is a rare disease accounting for almost 1% of all cancers in men and less than 1% of breast cancer. Emerging data on the genetic drivers of predisposition for MBC are available and different risk factors have been associated with its pathogenesis. Genetic alterations, such as pathogenetic variants in BRCA1/2 and other moderate-/low-penetrance genes, along with non-genetic risk factors, have been recognized as pathogenic factors for MBC. Preventive and therapeutic implications could be related to the detection of alterations in predisposing genes, especially BRCA1/2, and to the identification of oncogenic drivers different from FBC. However, approved treatments for MBC remain the same as FBC. Cancer genetic counseling has to be considered in the diagnostic work-up of MBC with or without positive oncological family history. Here, we review the literature, reporting recent data about this malignancy with a specific focus on epidemiology, and genetic and non-genetic risk factors. We introduce the perspective of cancer genetic counseling for MBC patients and their healthy at-risk family members, with a focus on different hereditary cancer syndromes.