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Meta-Analysis
. 2016 Oct;95(40):e4975.
doi: 10.1097/MD.0000000000004975.

Effect of BRCA germline mutations on breast cancer prognosis: A systematic review and meta-analysis

Zora Baretta  1 , Simone Mocellin, Elena Goldin, Olufunmilayo I Olopade, Dezheng Huo
Affiliations
Meta-Analysis

Effect of BRCA germline mutations on breast cancer prognosis: A systematic review and meta-analysis

Zora Baretta et al. Medicine (Baltimore). 2016 Oct.

Abstract

Background: The contribution of BRCA germline mutational status to breast cancer patients' prognosis is unclear. We aimed to systematically review and perform meta-analysis of the available evidence of effects of BRCA germline mutations on multiple survival outcomes of breast cancer patients as a whole and in specific subgroups of interest, including those with triple negative breast cancer, those with Ashkenazi Jewish ancestry, and patients with stage I-III disease.

Methods: Sixty studies met all inclusion criteria and were considered for this meta-analysis. These studies involved 105,220 breast cancer patients, whose 3588 (3.4%) were BRCA mutations carriers. The associations between BRCA genes mutational status and overall survival (OS), breast cancer-specific survival (BCSS), recurrence-free survival (RFS), and distant metastasis-free survival (DMFS) were evaluated using random-effect models.

Results: BRCA1 mutation carriers have worse OS than BRCA-negative/sporadic cases (hazard ratio, HR 1.30, 95% CI: 1.11-1.52) and worse BCSS than sporadic/BRCA-negative cases among patients with stage I-III breast cancer (HR 1.45, 95% CI: 1.01-2.07). BRCA2 mutation carriers have worse BCSS than sporadic/BRCA-negative cases (HR 1.29, 95% CI: 1.03-1.62), although they have similar OS. Among triple negative breast cancer, BRCA1/2 mutations carriers had better OS than BRCA-negative counterpart (HR 0.49, 95% CI: 0.26-0.92). Among Ashkenazi Jewish women, BRCA1/2 mutations carriers presented higher risk of death from breast cancer (HR 1.44, 95% CI: 1.05-1.97) and of distant metastases (HR 1.82, 95% CI: 1.05-3.16) than sporadic/BRCA-negative patients.

Conclusion: Our results support the evaluation of BRCA mutational status in patients with high risk of harboring BRCA germline mutations to better define the prognosis of breast cancer in these patients.

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Conflict of interest statement

The authors have no conflicts of interest to disclose.

Figures

Figure 1
Figure 1
Forrest plot of overall survival by BRCA mutational status.
Figure 2
Figure 2
Forrest plot of breast cancer-specific survival by BRCA mutational status.
Figure 3
Figure 3
Forrest plot of recurrence-free survival by BRCA mutational status.
Figure 4
Figure 4
Forrest plot of distant metastasis-free survival by BRCA mutational status.
See this image and copyright information in PMC

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