Survival in advanced-stage ovarian cancer patients with non-Ashkenazi Jewish BRCA mutations

Abstract

5514 Background: Previous studies have shown a survival advantage in ovarian cancer patients with Ashkenazi-Jewish BRCA founder mutations compared to sporadic ovarian cancer patients. The purpose of this study is to determine if this association exists in ovarian cancer patients with non- Ashkenazi Jewish (non-AJ) BRCA1 or BRCA2 mutations. Methods: Patients with stage III or IV ovarian, fallopian tube, or primary peritoneal cancer and a BRCA1 or BRCA2 mutation, seen for genetic testing between January 1996 and October 2006, were identified from the institutional and genetics databases. Medical records were reviewed for clinical factors including response to initial chemotherapy. Response is defined as no clinical evidence of disease with normalization of serum CA-125 and no radiographic evidence of disease or a negative second-look surgery. Patients with sporadic ovarian cancer, without a family history of breast or ovarian cancer, were compared to similar cases, matched by age, stage, and year of diagnosis. Progression-free and overall survival were calculated by the method of Kaplan-Meier. Chi-square tests and univariate logistic regression were also used in the data analysis. Results: Thirty-nine advanced-stage ovarian cancer patients with non-AJ BRCA mutations and 47 matched, advanced-stage sporadic ovarian cancer patients have been analyzed. Compared to patients with sporadic ovarian cancer, non-AJ BRCA mutation carriers had a longer progression-free survival (PFS, 32.4 mos. vs. 22.1 mos., p = 0.0303) and overall survival (OS, 101.4 mos. vs. 51.3 mos., p < 0.001). Similarly, 72% of the non-AJ BRCA mutation carriers had a complete response to initial treatment, compared to 45% of the sporadic ovarian cancer patients (p = 0.01). The odds of complete response to initial treatment were 3.2 times greater in the non-AJ BRCA group than in the sporadic group (OR 3.2; 95% CI 1.27 - 8.15). Conclusions: This study demonstrates a significant survival advantage in advanced-stage ovarian cancer patients with non-AJ BRCA mutations when compared to similar patients with sporadic ovarian cancer. Response to initial treatment appears to impact this improved survival. No significant financial relationships to disclose.