Analysis of the Clinical Advancements for BRCA-Related Malignancies Highlights the Lack of Treatment Evidence for BRCA-Positive Male Breast Cancer

SIMPLE SUMMARY: Male breast cancer (MBC) is an orphan disease that is on the rise but remains understudied. Mutations in genes sensitive to DNA damage response, BRCA1 and BRCA2, are strongly implicated in MBC development. Evidence-based guidance for the treatment of MBC that have BRCA mutations is lacking with most published data arising from retrospective or case studies with small patient cohorts. Here, we review the lack of treatment evidence for BRCA-related MBC. We also highlight the impact of poly(ADP-ribose) polymerase (PARP) inhibitors which are used in the clinical management of BRCA-related female breast cancer and prostate cancer. In turn, we demonstrate the requirement for national and global collaborative efforts to address the striking unmet need for dedicated BRCA-related MBC research, including studies to better understand disease trajectory and improve clinical outcomes. ABSTRACT: Male breast cancer (MBC) is a rare disease that accounts for less than 1% of all breast cancers and male malignancies. Despite recognised clinico-pathological and molecular differences to female breast cancer (FBC), the clinical management of MBC follows established FBC treatment strategies. Loss of function mutations in the DNA damage response genes BRCA1 and BRCA2, have been strongly implicated in the pathogenesis of MBC. While there have been extensive clinical advancements in other BRCA-related malignancies, including FBC, improvements in MBC remain stagnant. Here we present a review that highlights the lack of treatment evidence for BRCA-related MBC and the required national and global collaborative effort to address this unmet need. In doing so, we summarise the transformative clinical advancements with poly(ADP-ribose) polymerase (PARP) inhibitors in other BRCA-related cancers namely, FBC and prostate cancer.