Prognostic significance ofBRCAmutations in ovarian cancer: an updated systematic review with meta-analysis

// Kai Xu 1, * , Shouhua Yang 2, * , Yingchao Zhao 3 1 Department of Otolaryngology-Head and Neck Surgery, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, Hubei Province, China 2 Department of Obstetrics and Gynecology, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, Hubei Province, China 3 Cancer Center, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, Hubei Province, China * These authors contributed equally to this work Correspondence to: Yingchao Zhao, email: yingchaozhao321@126.com Keywords: ovarian cancer, BRCA mutation, prognosis, systematic review, meta-analysis Received: June 29, 2016      Accepted: September 22, 2016      Published: September 28, 2016 ABSTRACT There is no consensus on the syntheses concerning the impact of BRCA mutation on ovarian cancer survival. A systematic review and meta-analysis of observational studies was conducted that evaluated the impact of BRCA mutations on the survival outcomes of patients with ovarian cancer. The primary outcome measure was overall survival (OS) and secondary outcome was progression-free survival (PFS). We presented data with hazard ratios (HRs) and 95% confidence interval (CI) and pooled them using the random-effects models. From 2,624 unique records, 34 eligible studies including 18,396 patients were identified. BRCA1/2 mutations demonstrated both OS and PFS benefits in patients with ovarian cancer (OS: HR = 0.67, 95% CI, 0.57 to 0.78, I 2 = 76.5%, P <0.001; PFS: HR = 0.62, 95% CI, 0.53 to 0.73, I 2 = 18.1%, P = 0.261). For BRCA1 mutation carriers, the HRs for OS and PFS benefits were 0.73 (95% CI, 0.63 to 0.86) and 0.68 (95% CI, 0.52 to 0.89), respectively. For BRCA2 mutation carriers, the HRs for OS and PFS benefits were 0.57 (95% CI, 0.45 to 0.73) and 0.48 (95% CI, 0.30 to 0.75), respectively. The results of subgroup analyses for OS stratified by study quality, tumor stage, study design, sample size, number of research center, duration of follow-up, baseline characteristics adjusted and tumor histology were mostly constant across BRCA1/2 , BRCA1 and BRCA2 mutation subtypes. In summary, for patients with ovarian cancer, BRCA mutations were associated with improved OS and PFS. Further large-scale prospective cohort studies should be conducted to test its benefits in specific patients.