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).
In conclusion, ductal carcinoma in situ is the most commonly observed precursor lesion in male breast cancer and its presence seems to be associated with a better outcome, in particular in Luminal B HER2+ cases.
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.
This review critically discusses the recent developments in the study of male breast cancer in relation to ERα and AR action and highlights the potential future studies to further elucidate the genomic regulation of this rare disease.
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.
Somatic mutations and gene amplification were found only in BRCA1/2 mutation negative MBCs.Significant associations emerged between EGFR amplification and large tumor size (T4), ER-negative and HER2-positive status, between CCND1 amplification and HER2-positive and MIB1-positive status, and between ESR1 deletion and ER-negative status.Our results show that amplification of targetable oncogenes is frequent in BRCA1/2 mutation negative MBCs and may identify MBC subsets characterized by aggressive phenotype that may benefit from potential targeted therapeutic approaches.
Mutation carriers in BRCA1 families were not at increased risk of cancer, whereas mutation carriers in BRCA2 families were at increased risk of male breast cancer and prostate cancer with cumulative risks of 12.5% and 18.8%, respectively.
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.
Two classifications of Female Breast Cancer (FBC) subgroups (based in ER, PR, HER2, 2000 classification, and in ER, PR, HER2, ki67, 2013 classification) were used to achieve their prognostic value in MBC patients.
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 carried out comprehensive whole gene RNA analysis on 45 high-risk breast/ovary and male breast cancer families with no identified pathogenic variant on exonic sequencing and copy number analysis of BRCA1/2.
However, only about 10 % of MBCs are caused by BRCA1/2 germ-line mutations, while the largest part are sporadic cancers and may derive from somatic alterations.
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.
On the basis of the largest series analysed to date, our results show that BRCA1/2 MBCs display distinct pathologic characteristics compared with BRCA1/2 FBCs, and we identified a specific BRCA2-associated MBC phenotype characterised by a variable suggesting greater biological aggressiveness (i.e., high histologic grade).
Somatic mutations and gene amplification were found only in BRCA1/2 mutation negative MBCs.Significant associations emerged between EGFR amplification and large tumor size (T4), ER-negative and HER2-positive status, between CCND1 amplification and HER2-positive and MIB1-positive status, and between ESR1 deletion and ER-negative status.Our results show that amplification of targetable oncogenes is frequent in BRCA1/2 mutation negative MBCs and may identify MBC subsets characterized by aggressive phenotype that may benefit from potential targeted therapeutic approaches.