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.
The aim of this study was to investigate the role of the X chromosome gain in the development of MBC and its relation with AR gene copy number and expression.The X chromosome status was assessed in 66 cases of male invasive and in situ duct breast carcinoma, in 34 cases of gynecomastia associated with cancer, and in 11 cases of tumor-free gynecomastia.
Body mass index (P = .023) and DACH1 (P = .034) were correlated with MBC prognosis, whereas the expression of AR (P = .049), SIX1 (P = .048), surgery (P < .001), and chemotherapy (P = .001) were important for FBC in addition to already known factors: tumor size and location, TNM stage (lymph nodes and organ metastasis), radiotherapy, and ER and human epidermalgrowth factor receptor-2 (HER2) expression.
Not only the estrogen receptor (ER), but also other steroid hormone receptors, including the androgen receptor (AR) and progesterone receptor (PgR) are expressed in MBC.
The presence of long CAG repeat sequence and AR-positive expression were associated with shorter survival of MBC patients (CAG repeat: P = 0.050 for 5y-OS; P = 0.035 for 5y-DFS AR status: P = 0.048 for 5y-OS; P = 0.029 for 5y-DFS, respectively).
Moreover, an analysis of genes correlated to steroid receptors and ERBB2 suggested a prominent role for the androgen receptor in MBC with a minor relevance for progesterone receptor and ERBB2, although, similarly to FBC, a genomic amplification could be observed.
The clinical management of male breast carcinoma is considered, in particular the potential role of aromatase inhibitors and fulvestrant and targeting pathways involving prolactin and androgen receptor.
Forty one male breast cancer samples were studied, including one sample from a man with spinal and bulbar muscular atrophy (SBMA), which is caused by an AR CAG repeat expansion.
The entire coding region of the BRCA2 gene and two exons of the AR gene were analyzed for germ-line mutations to evaluate the association between BRCA2 and AR genes and male breast cancer in Poland.
Some AR ZFR point mutations observed in patients with partial androgen insensitivity syndrome or male breast cancer impair the interaction of AR with SNURF and also render AR refractory to the transcription-activating effect of SNURF.
Arg607-Gln and Arg608-Lys point mutations in the DNA-binding domain of the AR gene have been associated with male breast cancer in partial androgen insensitivity syndrome.
Two heritable gene defects have been associated with a predisposition to male breast cancer development, ie., germ-line mutations in the breast cancer susceptibility gene BRCA2 and the androgen receptor (AR) gene.
Moreover, androgen receptor gene alterations have been recently described in two unrelated diseases: male breast cancer and spinal and bulbar muscular atrophy.
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.