BRCA2 mutations should be screened early and routinely as markers of poor prognosis: evidence from 8,988 patients with prostate cancer.

Ming Cui,Yun Bai,Mu Xie,Chuan Peng,Shangbin Qin,Xiaobin Gu,Xin Qi,Xian-Shu Gao,Xiaoying Li,Wei Guo,Mingwei Ma

doi:10.18632/oncotarget.16712

Ming Cui, Yun Bai + Show 9 more

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https://doi.org/10.18632/oncotarget.16712

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Abstract

The aim of this study was to focus on clinicopathological characteristics and prognosis in men with prostate cancer (PCa) harboring a breast cancer 2 (BRCA2) gene mutation and to offer convincing evidence to consider BRCA2 mutation as a marker of poor prognosis in the molecular classification of PCa. We searched relevant articles from PubMed, Embase, Web of Science, and the Cochrane Library databases to evaluate the differences in the overall survival (OS) and cancer-specific survival (CSS) between BRCA2 mutation carriers and non-carriers in patients with PCa. We included 525 BRCA2 mutation-carriers and 8,463 non-carriers in total from 10 studies in our meta-analysis. The results showed that carrying a BRCA2 mutation was correlated with a reduced CSS and OS when compared with that of non-carriers, with pooled Hazard Ratios (HRs) of 2.53 (95% confidence interval (CI): 2.10–3.06, P < 0.001) and 2.21 (95% CI: 1.64–2.99, P < 0.001), respectively. The results also demonstrated that BRCA2 mutation-carriers harbored a higher Gleason Score (GS) (> 7), TNM stage (> T3, N1, M1), and risk level than non-carriers. Our meta-analysis showed that a BRCA2 mutation predicted poor survival outcomes in patients with prostate cancer, especially in those undergoing treatments with radiotherapy. Therefore, the use of BRCA2 mutation as a clinical prognostic factor could help stratify the high-risk patients and provide clinical strategies for more effective targeted treatments for patients with prostate cancer.

Highlights

Prostate cancer (PCa) was the most prevalent cancer among males in the United States in 2016 [1]
To the best of our knowledge, this is the first meta-analysis that concentrated on prostate cancer (PCa) screening and prognosis with in patients with breast cancer 2 (BRCA2) mutations
In this meta-analysis, we demonstrated that a BRCA2 mutation predicted a lower survival in patients with PCa, both for Caucasians and Asian

Summary

Introduction

Prostate cancer (PCa) was the most prevalent cancer among males in the United States in 2016 [1]. PCa is associated with age, prostate-specific antigen (PSA) levels, the Gleason score (GS), and the TNM stage, and with family history, especially when female relatives have a history of breast and/or ovarian cancer [2]. Evolution into castration-resistant prostate cancer (CRPC) following hormone therapy is observed in an increasing number of patients. Conventional chemotherapy does not show promising outcomes in CRPC patients with a germline breast cancer 2 (BRCA2) mutation. The BRCA2 mutation is rare and only occurs in approximately 2% of the population with earlyonset PCa [3], it increases the risk of PCa by about six times [4,5,6]. PCa patients with a BRCA2 mutation have a higher GS scores and have poorer survival outcomes than non-carriers [7, 8]

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Conclusion