BRCA mutations and survival in breast cancer: an updated systematic review and meta-analysis
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Yaning Zhu1, Jian Wu1, Chengwan Zhang2, Suan Sun1, Jian Zhang3, Wenjie Liu1, Jian Huang1, Zhihong Zhang4
1Department of Pathology, Huai’an First People’s Hospital, Nanjing Medical University, Huai’an, Jiangsu Province, China
2The Central Laboratory of Huai’an First People’s Hospital, Nanjing Medical University, Huai’an, Jiangsu Province, China
3Department of Breast Surgery, Huai’an First People’s Hospital, Nanjing Medical University, Huai’an, Jiangsu Province, China
4Department of Pathology, the First Affiliated Hospital of Nanjing Medical University, Nanjing, Jiangsu Province, China
Zhihong Zhang, email: [email protected]
Chengwan Zhang, email: [email protected]
Keywords: breast cancer, BRCA mutation, survival, systematic review, meta-analysis
Received: March 15, 2016 Accepted: September 13, 2016 Published: September 21, 2016
BRCA mutations occur frequently in breast cancer (BC), but their prognostic impact on outcomes of BC has not been determined. We conducted an updated meta-analysis on the association between BRCA mutations and survival in patients with BC. Electronic databases were searched. The primary outcome measure was overall survival (OS), and the secondary outcome measures included breast cancer-specific survival (BCSS) and event-free survival (EFS). Hazard ratios (HR) and 95% confidence interval (CI) were abstracted and pooled with random-effect modeling. Data from 297, 402 patients with BC were pooled from 34 studies. The median prevalence rates of BRCA1 and BRCA2 mutations were 14.5% and 8.3%, respectively. BRCA mutations were associated with worse OS (BRCA1: HR = 1.69, 95% CI, 1.35 to 2.12, p < 0.001; BRCA2: HR = 1.50, 95% CI 1.03 to 2.19, p = 0.034). However, this did not translate into poor BCSS (BRCA1: HR = 1.14, 95% CI, 0.81 to 1.16, p = 0.448; BRCA2: HR = 1.16; 95% CI 0.82 to 1.66, p = 0.401) or EFS (BRCA1: HR = 1.10, 95% CI, 0.86 to 1.41, p = 0.438; BRCA2: HR= 1.09; 95% CI 0.81 to 1.47, p = 0.558). Several studies analyzed BRCA1 and BRCA2 mutations together and found no impact on OS (HR = 1.21; 95% CI, 0.73 to 2.00, p = 0.454) or EFS (HR = 0.94; 95% CI, 0.60 to 1.48, p = 0.787). BRCA1 and BRCA2 mutations were associated with poor OS in patients with BC, but had no significant impact on BCSS or EFS. An improved survival was observed in BC patients who had BRCA1 mutation and treated with endocrinotherapy. The results may have therapeutic and prognostic implications important for BRCA mutation carriers with BC.
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