Correlation of BRCA and homologous recombination deficiency status with clinical and survival outcomes in patients with advanced-stage ovarian cancer undergoing frontline therapy.

Overall, 50% of patients with ovarian cancer harbor a BRCA1/BRCA2 mutation or have tumors characterized by homologous recombination deficiency (HRD). We hypothesized that germline BRCA-positive or somatic BRCA+/HRD+ status would be associated with improved survival compared to BRCA-negative (BRCA-)/HRD- status. We performed a retrospective analysis of patients with advanced high-grade ovarian cancer treated from April 2013 to June 2019 and had known germline BRCA and HRD status. Clinical outcomes were stratified by (1) germline BRCA+ (2) germline BRCA- and somatic BRCA+/HRD+, or (3) BRCA-/HRD- status. Progression free and overall survival were estimated using Kaplan-Meier methods stratified by HRD status and modeled via Cox proportional hazards regression. A total of 187 patients met the inclusion criteria: 55 were BRCA-/HRD-, 106 were germline BRCA+, and 26 were somatic BRCA+/HRD+. HRD- tumors had more non-serous histology (20% vs 6% and 0%, p = .04), were less likely to have complete gross resection (R0) at tumor reductive surgery (60% vs 83% and 77%, p = .02) and required more neoadjuvant chemotherapy cycles (4 vs 3 and 3 cycles, p = .03). Patients with BRCA-/HRD- status had worse progression free survival (14.9 months) than those with germline BRCA+ (23.5 months) or somatic BRCA+/HRD+ (20.2 months, p < .001). Patients with BRCA-/HRD- status also had worse overall survival (42.3 months) than those with germline BRCA+ (68.8 months) or somatic BRCA+/HRD+ (69.2 months). On multi-variate analysis, R0 resection at tumor reductive surgery (hazard ratio [HR] 2.83, 95% confidence interval [CI] 1.58 to 5.06, p < .001), and BRCA+/HRD- status (HR 0.52, 95% CI 0.36 to 0.74, p < .001) were significant factors impacting progression free survival. Tumor reductive surgery (HR 0.15, 95% CI 0.07 to 0.31), and BRCA-/ HRD- (HR 2.25, 95% CI 1.08 to 4.70, p = .03) were significantly associated with overall survival. g/sBRCA+/HRD+ ovarian cancer status is associated with improved survival regardless of primary tumor reductive surgery or neoadjuvant chemotherapy. BRCA-/HRD- status is an adverse prognostic factor for survival.