Young Israeli women with epithelial ovarian cancer: prevalence of BRCA mutations and clinical correlates

Abstract

Objective: The current study investigates disease patterns and outcomes in young Israeli epithelial ovarian cancer (EOC) patients and their association with BRCA mutation status.

Methods: Consecutive EOC patients diagnosed at or below 50 years in a single institution between 1995-2011 were identified. All patients are referred for genetic counseling and testing for the predominant Jewish BRCA mutations: BRCA1-185delAG, BRCA1-5382insC, and BRCA2-6174delT. A comparison between BRCA mutation carriers and non-carriers was undertaken across demographic, pathologic, and clinical features; recurrence and survival were compared using the Kaplan-Meier method and associations with the variables of interest were analyzed using the Cox proportional hazards method.

Results: One hundred eighty-six patients diagnosed with EOC at 50 years or younger were included, with a total follow-up of 1,088 person years. Mean age at diagnosis was 44±5 years. Of 113 patients with documented BRCA testing, 49.6% carried a germline BRCA mutation, compared with 29% in the general Israeli EOC population (p=0.001). BRCA mutation carriers had a higher rate of serous tumors (75% vs. 64%, p=0.040) and higher CA125 levels at diagnosis (median, 401 vs. 157, p=0.001) than non-carriers. No significant association between BRCA mutations and recurrence (hazard ratio [HR]=1.03; p=0.940) or survival (HR=1.40; p=0.390) was found.

Conclusion: BRCA mutations are encountered in almost 50% of young Israeli ovarian cancer patients; they are associated with serous tumors and high CA125 levels at diagnosis, but are not independently associated with recurrence or survival in this patient population.

Keywords: BRCA1; BRCA2; Glandular and Epithelial Neoplasms; Ovarian Neoplasms; Women; Young Adult.

Fig. 1

CA125 levels in BRCA mutation carriers vs. non-carriers. CA125 levels in BRCA mutation carriers were significantly higher at diagnosis (median, 401 vs. 157; p=0.001) and had a wider interquartile range (122–1,100 vs. 39–415).

Fig. 2

DFS (A) and OS (B) in BRCA mutation carriers vs. non-carriers. Median DFS was 46.2 months for non-carriers and 73.4 months for BRCA mutation carriers (p=0.910); median OS was not reached for non-carriers and was 213.7 months for BRCA mutation carriers (p=0.730). DFS, disease-free survival; OS, overall survival.

Fig. 3

DFS (A) and OS (B) in advanced, high-grade serous, and endometrioid ovarian cancer: BRCA mutation carriers vs. non-carriers. Disease outcome in a subpopulation of patients with advanced (stage III–IV), high-grade serous, or endometrioid ovarian tumors. Median DFS was 20.9 months for non-carriers and 21.2 months for BRCA mutation carriers (p=0.220); median OS was 63.5 months for non-carriers and 71.9 months for BRCA mutation carriers (p=0.720). DFS, disease-free survival; OS, overall survival.