Male BC is almost exclusively hormone receptor positive (+), including the androgen receptor (AR), and is associated with an increased prevalence of BRCA2 germline mutations, especially in men with increased risk for developing high-risk BC.
Several susceptibility genes have been established for female breast cancer, of which mutations in BRCA1 and especially in BRCA2 are also known risk factors for male breast cancer (MBC).
Cluster analysis showed MBCs arising in BRCA2 mutation carriers were characterised by RASSF1A, WIF1, RARβ and GTSP1 methylation (p = 0.02) whereas methylation in BRCAX tumours showed no clear clustering to particular genes.
Pathogenic variants in BRCA2 [odds ratio (OR) = 13.9; p = 1.92 × 10<sup>-16</sup>], CHEK2 (OR = 3.7; p = 6.24 × 10<sup>-24</sup>), and PALB2 (OR = 6.6, p = 0.01) were associated with significantly increased risks of MBC.
Early age at diagnosis of breast cancer, ovarian cancer, bilateral breast cancer were associated with BRCA1, whereas male breast cancer and four or more breast cancer cases in the family were associated with BRCA2.
Breast cancer is rare in male patients.Certain predisposing factors, be they genetic (e.g., BRCA2 gene mutations) or hormonal (imbalance between estrogen and androgen levels), have been implicated in male breast cancer pathophysiology.
We also discuss guidelines on screening and management for other cancers associated with BRCA1 and BRCA2, such as male breast cancer, pancreatic cancer, and prostate cancer.
The current literature suggests that genetic factors including BRCA2 mutations, family history, age, androgen/estrogen imbalance, and environmental exposures may predispose to male breast cancer.
Thus, it can be hypothesized that in a proportion of MBCs, particularly in BRCA2-associated MBCs, the level of estrogens and environmental carcinogens exposure might be increased suggesting a link between gene and environmental exposure in the pathogenesis of MBC.
We report a case of male breast carcinoma in a patient with the BRCA2 mutation detected by screening mammography, and review the literature regarding screening mammography in men.
Therefore, we wanted to investigate the contribution of germline PALB2 mutations in a set of 131 Spanish BRCA1/BRCA2-negative breast/ovarian cancer families with at least one male breast cancer case.
Based on our results and previous studies, genetic testing for BRCA2 should be recommended for any diagnosed MBC case, regardless of family history of breast cancer.
Heterozygous germ line mutations in the Breast CAncer1 (BRCA1) and BRCA2 genes can lead to a high risk of breast and ovarian cancer, in addition to a significantly increased susceptibility of pancreatic, prostate and male breast cancer.