Fifteen-year Survival of Invasive Epithelial Ovarian Cancer in Women with BRCA1/2 Mutations - the National Israeli Study of Ovarian Cancer

Objective: Compare 5, 10 and 15 year survival in invasive epithelial ovarian cancer, between patients with and without BRCA1/2 germ line mutation in a nonselective group of patients diagnosed during 1994-99.

Methods: The analysis was based on 779 Jewish patients: 229 carriers to the Ashkenazi Jewish founder mutations in BRCA1 (185delAG; 5382insC) and BRCA2 (6174delT); and 550 non-carriers. Clinical characteristics were abstracted from the patients' medical records and vital status was updated through the National Population Registry up to 11/2015. The Kaplan-Meier method, log-rank tests, and Cox-regression model were used for survival analyses.

Results: By the end of the follow-up period, (range 1-20 years), 629 (80.7%) deaths occurred. While considerably higher survival was observed during the first 5 years from diagnosis among carriers compared to non-carriers (46.7% vs. 36.2%, p = 0.0004), the survival rates at 15 years were 22.3% vs. 21.8% respectively (p = 0.04). The age-adjusted hazard ratio for all-cause mortality of carriers versus non-carriers was 0.74 (95%CI 0.60-0.91) in the first 5 years. For women who survived 5 and 10 years, the age-adjusted hazard ratios for mortality during 5 additional years, of carriers compared to non-carriers, were 1.38 (95%CI 0.93-2.04) and 1.08 (95%CI 0.61-1.92), respectively.

Conclusion: The results of this study, with up to 20 years follow-up, support studies with shorter follow-up that suggested that the advantage in survival observed among BRCA1/2 carriers during the first 5 years decreases over time. Clinically, this may have implications for follow-up and therapy, especially of new agents that are particularly effective in BRCA carriers.