BRCA2 Mutations in Prostate Cancer: A Literature Review

Abstract

Background: Prostate cancer is one of the most frequently diagnosed neoplastic disease and the second leading cause of cancer mortality in men of the Western world. Despite improved methods for early detection, a large proportion of patients succumb to metastatic prostate cancer that is resistant to conventional therapies. The development of novel effective strategies to prevent and treat prostate cancer relies considerably upon increasing our knowledge of the interplay among various molecular and genetic alterations that lead to onset and progression of prostate cancer. To date, germline mutations in the cancer susceptibility gene BRCA2 represent one of the strongest risk factor to develop prostate cancer.

Objective: Goal of this review is to summarize current reports investigating the presence of BRCA2 mutations in prostate cancer.

Design: A comprehensive analysis of the literature on BRCA2 mutations in prostate cancer. Data source: Pubmed. Terms included in the search: "BRCA2 mutations", "prostate cancer".

Results: A total of 18 studies were included in the review. The studies focused on the clinical implications of BRCA2 mutations in prostate cancer. The findings indicate that inherited pathogenic mutations in BRCA2 predispose to highly aggressive prostate cancers and poor survival. Very recent reports also suggest that metastatic castration-resistant prostate cancers are "enriched" of BRCA2 mutations compared to the primary tumors.

Conclusion: Because BRCA2-mutated tumors are very sensitive to PARP-inhibitors'-based chemotherapy, BRCA2 genomic testing of patients with advanced metastatic prostate disease may enable an effective, personalized, therapeutic strategy.