The “BRCAness” syndrome in ovarian cancer: A case-control study describing the clinical features and outcome of patients with epithelial ovarian cancer associated with BRCA 1/2 mutations

Abstract

5594 Background: We evaluated the clinical impact of germline BRCA1/2 mutations in patients with epithelial ovarian cancer (EOC) on responses to 1st and subsequent lines of chemotherapy, treatment-free interval (TFI) between each line of therapy and overall survival (OS). Methods: Twenty-two EOC patients with germ-line BRCA1 or BRCA2 mutations (BRCA+) were selected from the Royal Marsden Hospital clinical genetics database and matched (1:2) with 44 non-hereditary EOC controls for stage, histological subtype, age at diagnosis, and year of diagnosis. Non-hereditary EOC patients were defined by no associated personal history of breast cancer and no family history of breast and ovarian cancer (n=36) or by an uninformative BRCA mutation test (n=8). All patients received primary platinum-based chemotherapy. Statistical analysis was performed using a Kaplan-Meier method and log-rank test. Cox regression analysis was used to identify independent prognostic factors. Responses after first, second, and third line treatment were compared between groups using the Chi-squared and Fisher's exact test. Results: BRCA+ EOC patients had higher overall (95.5% vs 59.1%, p=0.002) and complete response rates (81.8% vs 43.2%, p=0.004) to 1st line platinum-based treatment compared with non- hereditary EOC patients. They also were significantly more likely to respond to 2nd and 3rd line platinum-based chemotherapy (2nd line 91.7% vs 40.9%; p=0.004; 3rd line 100% vs 14.3%, p=0.005) and have longer TFIs. A significant improvement in median OS in BRCA+ compared with non-hereditary EOC groups was observed from both time of diagnosis (8.4 vs 2.9 years, p<0.002) and time of 1st relapse (5 vs 1.6 years, p<0.001). In a multivariate analysis BRCA status, stage, and length of first response were independent prognostic factors. Conclusions: Patients with BRCA+ EOC have better outcomes compared with non-hereditary EOC patients. A clinical syndrome of BRCAness exists which includes: high response rates to 1st and subsequent lines of platinum-based treatment, long TFIs between relapses and improved OS. This syndrome is a potential predictor of response to Poly (ADP-ribose) polymerase (PARP) inhibitor treatment. Author Disclosure Employment or Leadership Consultant or Advisory Role Stock Ownership Honoraria Research Expert Testimony Other Remuneration AstraZeneca educational grants from AstraZeneca