Although similar phenotypically, there is evidence that male and female breast cancer differ in their molecular landscapes. In this systematic review, we consolidated all existing prognostic biomarker data in male breast cancer spanning genetics, transcriptomics, proteomics, and epigenetics, and phenotypic features of prognostic value from articles published over a 29-year period (March 16, 1992, to May 1, 2021). We identified knowledge gaps in the existing literature, discussed limitations of the included studies, and outlined potential approaches for translational biomarker discovery and validation in male breast cancer. We also recognised STC2, DDX3, and DACH1 as underexploited markers of male-specific prognostic value in breast cancer. Finally, beyond describing the cumulative knowledge on the extensively researched markers oestrogen receptor-α, progesterone receptor, HER2, androgen receptor, and BRCA2, we highlighted ATM, CCND1, FGFR2, GATA3, HIF1-α, MDM2, TP53, and c-Myc as well studied predictors of poor survival that also aligned with several hallmarks of cancer.
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