ASCO 2018: The Association of BRCA1 and BRCA2 Mutations on Prostate Cancer Risk, Frequency, and Mortality: Systematic Review and Meta-Analysis

Chicago, IL ( The impact on genome alterations in DNA repair genes, including BRCA1 and BRCA2, have gained significant attention in the setting of prostate cancer in the past few decades. Patients with BRCA mutations appear to have more aggressive prostate cancer, as suggested by a few separate series and published studies. Family history of BRCA mutations is now an important clinical assessment as it may affect patient management.

Yet, as the authors of this study note, one earlier prior meta-analysis1 in 2011 did not find that BRCA1 mutations were associated with increased prostate cancer risk. They only looked at BRCA1, which may be why it was negative. However, since that time, many series have been published demonstrating a positive association with BRCA status and prostate cancer risk and mortality.

To address this discrepancy, the authors completed an updated meta-analysis (PRISMA guidelines) of all published studies in the space, encompassing all BRCA1 and BRCA2 studies; they searched the PubMed/MEDLINE, Embase and Cochrane databases. Their aim was to estimate PCa risk in BRCA mutation carriers, evaluate the frequency of BRCA mutation carriers in PCa patients (pts) and compare survival rate among BRCA mutation carriers and non-carriers.

From over 200 studies, they identified 69 total relevant studies: 11 cohort, 7 case-control, 4 case-series, 30 frequency and 11 survival studies.

What did they find? BRCA carrier status was associated with a significant increase in PCa risk (OR 1.91, p<0.005)); BRCA2 mutation was associated with a greater risk of PCa (OR 2.64, p<0.005) than BRCA1 (OR 1.35, p=0.03).

How often were these mutations found in PCa patients? The frequency of BRCA1 and BRCA2 carriers in PCa patients was 1.1% and 2.5% respectively. This is higher than the general population.

As for association with clinical outcomes, patients with BRCA2 mutations had worse OS (HR 2.21, 95%CI 1.64-2.30) and worse CSS (HR 2.63, 95%CI 2.00-3.45). However, BRCA1 carriers had no significant difference in OS (HR 0.47, 95%CI 0.11-1.99) or CSS (HR 1.07, 95%CI 0.38-2.96).

Based on this more recent meta-analysis, BRCA mutations result in a 1.91-fold greater risk of prostate cancer, which is specifically driven by a large 2.64-fold greater risk in BRCA2 carriers and a moderate 1.35-fold greater risk in BRCA1 carriers. Carried forward, BRCA2, but not BRCA1, mutations were associated with higher PCa mortality.

Therefore, BRCA mutation, and BRCA2 in particular, may be a clinical factor to stratify high-risk patients and provide clinical strategies for more effective targeted treatments for patients with PCa.

Presented by: Mok Oh, MD

Written by: Thenappan Chandrasekar, MD, Clinical Fellow, University of Toronto, Twitter: @tchandra_uromd at the 2018 ASCO Annual Meeting - June 1-5, 2018 – Chicago, IL USA

1. Fachal L et al. BRCA1 mutations do not increase prostate cancer risk: results from a meta-analysis including new data. Prostate. 2011 Dec;71(16):1768-79. doi: 10.1002/pros.21394. Epub 2011 Apr 25.