BRCA mutation testing and association with oncologic outcome and incidence of ovarian cancer in Norway.

Abstract

Objective: This study aimed to explore the frequency of BRCA mutations and testing, age at diagnosis, and incidence of ovarian cancer and to describe oncologic outcomes in patients carrying BRCA mutation compared with those not carrying mutation, in 1 cancer center that covers two-thirds of the Norwegian population.

Methods: Patients with ovarian cancer treated at Oslo University Hospital-Radiumhospital 2008-2019 who accepted BRCA testing were prospectively registered in the study. Patients carrying mutation and their families received genetic counseling and risk-reducing surgery. For patients treated from 2014 to 2019 (N = 1032), detailed clinicopathologic data (International Federation of Gynecology and Obstetrics stage, histopathology, type of surgery, residual disease, chemotherapy, first recurrence, and survival) were obtained. Overall and progression-free survival were analyzed using Kaplan-Meier curves and Cox regressions. Linear trends were assessed using linear regressions. Using data delivered by the Cancer Registry of Norway, we assessed ovarian cancer incidence in the uptake area of Oslo University Hospital-Radiumhospital throughout the study period.

Results: A total of 1579 patients were registered. Throughout the study period, BRCA mutation frequency was decreasing, from 14.5% to 6.8%, and mean age at diagnosis increasing, from 59.4 to 63.8 years, in 2008 and 2019, respectively. Patients carrying BRCA1 mutation were younger at diagnosis than were patients carrying BRCA2 mutation and those not carrying mutation. Patients carrying BRCA mutation had almost exclusively high-grade serous histology, and had more often advanced disease and higher cancer antigen 125 levels at the time of diagnosis and were more often treated with interval debulking surgery than were those not carrying mutation. Patients carrying BRCA2 mutation had better overall survival than did those not carrying mutation. The incidence rate of ovarian cancer was decreasing throughout the study, from 22 to 18 per 100,000 person-years in 2008 and 2019, respectively.

Conclusion: BRCA mutation testing in patients with ovarian cancer has become more widely incorporated into clinical practice over time, owing to its importance for prognosis and for risk-reducing measures in the families of patients carrying mutation, and possibly contributes to a decrease in ovarian cancer incidence.