Abstract
Male breast cancer (MBC) is a rare disease. Due to its rarity, MBC research and clinical approach are mostly based upon data derived from female breast cancer (FBC). Increasing evidence indicate that on molecular level MBC may be an heterogeneous disease different from FBC.In order to investigate whether epigenetic signatures could define molecular subgroups of MBCs, we performed promoter methylation analysis of genes involved in signal transduction and hormone signalling in BRCA1/2 mutation-positive and -negative MBCs.We examined 69 MBCs, paired blood samples, and 15 normal tissues for promoter methylation of hTERT, ESR1, RASSF1, AR, MYC and WNT1 genes.MBCs showed higher gene promoter methylation levels compared to paired blood and normal breast samples. Significantly higher RASSF1 methylation levels were observed in association with BRCA1/2 mutations, HER2 expression and high tumor grade. Significantly higher AR methylation levels were observed in BRCA1/2 wild-type cases and higher WNT1 methylation levels in PR negative cases.Overall, our results indicate that alterations in gene methylation profiles are common in MBC and that methylation pattern of tumor-associated genes may allow for the identification of MBC molecular subgroups, that could have implications in clinical management of MBC patients.
Highlights
In order to investigate whether epigenetic signatures could define molecular subgroups of Male breast cancer (MBC), we performed promoter methylation analysis of genes involved in signal transduction and hormone signalling in BRCA1/2 mutation-positive and -negative MBCs
We previously showed that BRCA mutation positive and BRCA mutation negative MBC cases display different phenotypic features, and in particular we identified a specific BRCA2-associated MBC phenotype characterized by higher tumor grade compared with MBC from the general population [26,27,28]
In this study we examined methylation profiles of BRCA mutation positive and BRCA mutation negative MBCs by performing promoter methylation analysis of a panel of breast cancer-related genes, in order to investigate whether epigenetic signatures could define molecular subgroups of MBCs
Summary
Male breast cancer (MBC) is a rare disease, representing less than 1% of all breast cancers and less of 1% of all male tumors [1]. Morbidity and mortality in MBC patients is a serious concern. MBC shares some similarities with post-menopausal ER-positive female breast cancer (FBC). Increasing evidence indicate that, on clinical and molecular level, MBC may be a heterogeneous disease, different from FBC [2,3,4]. MBC research and patient management are mostly based upon data derived from its largely known female counterpart. Mortality and survival rates for patients with MBC have improved less over time than for patients with FBC [5]. These data highlight the need to identify specific biological markers for MBC
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