Male breast cancer (MBC) accounts for approximately 1% of all breast cancer cases. Family history is an established risk factor for MBC and 10% of cases have germline BRCA2 mutations. We recently demonstrated that common germline polymorphisms contribute to MBC predisposition and that there is overlap between genetic susceptibility loci for MBC and female breast cancer (FBC).

Here we report a comprehensive evaluation of all 107 known FBC predisposition loci in an association analysis of 1,032 MBC cases and 2,795 population matched controls. A total of 21 FBC predisposition single nucleotide polymorphisms (SNPs) showed evidence of association with risk of MBC. For approximately a third of these SNPs, the risk estimates were significantly larger in MBC than FBC. The magnitude of effects observed suggest that common susceptibility variants may be of value for risk stratification in men who have a high absolute risk of breast cancer such as BRCA2 mutation carriers. Although our data suggests that MBC predisposition shares many features in common with FBC, there are striking differences. Surprisingly, given the predominance of hormone receptor positive tumors in MBC, we observed no evidence of association between SNPs at FGFR2 and MBC risk suggesting that the estrogen receptor status of MBC tumors does not explain the observed SNP associations.

In summary, the data presented in this abstract significantly advance our understanding of genetic factors that contribute to MBC predisposition and further underscore the growing consensus that male breast cancer is not simply analogous to hormone receptor positive female breast cancer.

Citation Format: Eleni Perrakis, Sarah Maguire, Katarzyna Tomczyk, Anthony Swerdlow, Nick Orr. Characterization of germline susceptibility to male breast cancer [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2017; 2017 Apr 1-5; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2017;77(13 Suppl):Abstract nr 1313. doi:10.1158/1538-7445.AM2017-1313