Abstract
Background:
Epithelial ovarian cancer is the deadliest gynecologic cancer in the world and most patients present at an advanced stage of disease. BRCA1 and BRCA2 gene germline mutations disrupt homologous recombination DNA repair processes and are correlated with a high response to platinum-based chemotherapy and targeted treatments. Several observational studies have suggested that ovarian cancers associated with the breast cancer genes (BRCA1/2 mutations) may show better survival than sporadic ovarian cancers; however, reported outcomes between studies are still variable.
Objective:
This systematic review and meta-analysis assessed the association between BRCA1/2 mutation status and survival and surgical outcomes in epithelial ovarian cancer, with a focus on overall survival (OS) and progression-free survival (PFS).
Methods:
A systematic review was performed based on the PRISMA 2020 guidelines. Observational cohort studies reporting survival outcomes in epithelial ovarian cancer patients stratified by their status for BRCA1/BRCA2 mutations, or "BRCA," were identified and included. There were seven identified eligible cohort studies that were incorporated into the quantitative synthesis: Gallagher et al. (2011), Vencken et al. (2011), Candido-dos-Reis et al. (2015), Yang et al. (2011), Kim et al. (2022), Hyman et al. (2012), and Unni et al. (2016). Extraction was done of hazard ratios (HRs) and 95% confidence interval (CI) of overall survival and progression-free survival. The pooled effect estimates were developed using random-effects meta-analysis models. The I2 statistic was used to test statistical heterogeneity.
Results:
Seven observational cohort studies were included in the systematic review and meta-analysis.
For overall survival among carriers of a mutation in the breast cancer gene (BRCA1), two studies contributed to the pooled analysis. The random-effects model showed a pooled hazard ratio of 0.69 (95% CI 0.45-1.04) as compared to non-carriers, which showed a tendency to have better survival though with a lot of heterogeneity (I2 = 83.7%).
For overall survival in persons who were carriers of the BRCA2 mutation, 3 studies contributed to the pooled estimate. The combined random-effects hazard ratio was 0.50 (95% CI 0.39-0.65), and the survival was significantly better than in sporadic ovarian cancer, and the heterogeneity was minimal (I2 = 15.1%).
For progression-free survival two studies on BRCA2 mutation carriers contributed to the pooled analysis. The combined hazard ratio was 0.42 (95% CI 0.26-0.67) which implied much longer progression-free survival of BRCA2 mutation carriers with no heterogeneity (I2 = 0).
In the covered studies, BRCA mutation carriers were also found to be more responsive to platinum-based chemotherapy and showed positive treatment outcome over their non-carrier counterparts.
Conclusion:
This meta-analysis shows that the presence of mutation in the breast cancer susceptibility gene (BRCA) has a significant impact on survival in epithelial ovarian cancer, especially in the case of mutation carriers of the gene (BRCA2) which have a significantly better overall survival and progression-free survival, compared with the sporadic case. These conclusions confirm the clinical relevance of genetic analysis and tailored treatment plans in the treatment of ovarian cancer.