Genetic Landscape of Male Breast Cancer

Abstract

Male breast cancer (MBC) is now considered molecularly different from female breast cancer (FBC). Evidence from studies indicates that common genetic and epigenetic features of FBC are not shared with those diagnosed in men. Genetic predisposition is likely to play a significant role in the tumorigenesis of this rare disease. Inherited germline variants in BRCA1 and BRCA2 account for around 2% and 10% of MBC cases, respectively, and the lifetime risk of breast cancer for men harboring BRCA1 and BRCA2 mutations is 1.2% and 6.8%. As for FBC, pathogenic mutations in other breast cancer genes have also been recently associated with an increased risk of MBC, such as PALB2 and CHEK2 mutations. However, while multigene germline panels have been extensively performed for BC female patients, the rarity of MBC has resulted in limited data to allow the understanding of the magnitude of risk and the contribution of recently identified moderate penetrance genes of FBC for MBC predisposition. This review gathers available data about the germline genetic landscape of men affected by breast cancer, estimated risk associated with these genetic variants, and current guidelines for clinical management.

Keywords: BRCA1; BRCA2; genetic testing; hereditary breast cancer; male breast cancer.

Figure 1

Frequency of the altered genes in luminal tumors from MBC and from breast cancer TCGA samples. First are percentages of the most common altered genes in the studies. Last are presented the frequencies of the most common altered DNA repair-related genes, besides TP53, which include ATM, ATR, BRCA2, BRCA1, and CHEK2.