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

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, I2 = 76.5%, P <0.001; PFS: HR = 0.62, 95% CI, 0.53 to 0.73, I2 = 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.

Treatment of recurrent epithelial ovarian cancer

“…5,27 BRCA1 and BRCA2 mutations are involved in the mechanism known as homologous recombination deficiency (HRD), by which cancer cells lack the ability to repair DNA double-strand breaks. 30 Maintenance with olaparib was the first PARP inhibitor treatment approved in Europe and was initially approved only for patients with mutations of the BRCA1 and BRCA2 genes. 28 BRCA1 and BRCA2 mutations can be found in approximately 20% of high-grade serous ovarian cancers: they are germline in two-thirds of cases and somatic in the remaining cases.…”

“…29 Patients harboring these mutations Cancer December 15, 2019 generally have platinum-sensitive disease and longer survival. 30 Maintenance with olaparib was the first PARP inhibitor treatment approved in Europe and was initially approved only for patients with mutations of the BRCA1 and BRCA2 genes. The first trial with olaparib, Study 19, was a randomized, double-blind, phase 2 study evaluating the use of the drug as maintenance therapy in patients with a partial or complete response to their last platinum-based chemotherapy.…”

Distinct implications of different BRCA mutations: efficacy of cytotoxic chemotherapy, PARP inhibition and clinical outcome in ovarian cancer

“…A recent meta-analysis of over 18,000 OC patients reported superior PFS in both BRCA1 - and BRCA2 -associated OCs 149. They reported HRs for PFS in BRCA1 - and BRCA2 -associated versus BRCA wild-type OC of 0.68 (95% CI, 0.52–0.89) and 0.48 (95% CI, 0.30–0.75), respectively.…”

Survival Benefit of Germline BRCA Mutation is Associated with Residual Disease in Ovarian Cancer

“…On the contrary, an updated meta-analysis including 18, 396 EOC patients debated that BRCA1/2 mutations, BRCA1 or BRCA2 mutation might only show a certain benefit of OS and PFS [10]. It might be more likely addressed to the better response to platinum-based chemotherapy for mutation carriers [17,18].…”

“…However, the updated descriptive survival analyses suggested that such a short-term progression-free survival (PFS) advantage of PARP inhibitor maintenance monotherapy did not lead to an overall survival benefit eventually [8], indicating a possible controversy of using BRCA mutations as the prognostic factor for long-term survival in ovarian cancer patients. Similarly, amounting evidence from studies including several meta-analyses has demonstrated that EOC patients carrying inherited BRCA1 or BRCA2 mutations have a better overall survival, compared with non-carriers [9,10]. However, more large-scale studies have suggested that the short-term survival advantage would not persist, when the patients were followed up 10 years [11,12].…”