Objectives The aim of this study was to investigate survival of

Objectives The aim of this study was to investigate survival of ovarian cancer patients with BRCA1 and BRCA2 mutations compared to those without mutations in a population-based sample of incident epithelial ovarian cancer cases. with either BRCA2 carriers or non-carriers. Conclusion These data buy 5-Iodotubercidin suggest that BRCA2 mutation carriers with ovarian cancer may have better survival than BRCA1 carriers and noncarriers. The etiology of this possible survival advantage is currently unknown. Larger studies are needed to confirm these results and to clarify their etiology and clinical significance. = 20 women), 58 years among BRCA2 carriers (= 12 women), and 57 years among women with invasive sporadic tumors (= 177). The distribution of histologic subtypes and stage of the TBOCS patients is usually shown in Table 1. The Wilcoxon rank sum test was performed to evaluate the association between stage and BRCA status, however the results were insignificant (= 0.29). Table 1 Tumor histology: subtype and Itgam stage among BRCA mutation carriers and noncarriers Survival analysis using Cox regression was initially performed on all 232 TBOCS cases (data not shown) and subsequently performed including only the 209 invasive epithelial ovarian cancer cases. Results of these two analyses buy 5-Iodotubercidin were comparable, thus results involving the 209 invasive epithelial cancer cases are shown, as this was judged to be more clinically relevant. Total observation time for all subjects was 4,083 months, with a median of 18.42 months. Variables examined in the univariate Cox regression analysis were age at diagnosis, BRCA status, grade, stage (early vs. late), and histologic subtype (serous vs. non-serous). Statistically significant associations buy 5-Iodotubercidin with survival were found for age at diagnosis (= 0.040), BRCA status (= 0.009), and stage (= 0.009). Variables identified as statistically significant in the univariate model were included in the multivariate analysis. In the multivariate analysis, the association of age at diagnosis with survival lost statistical significance, however BRCA status and stage remained statistically significant (Table 2). Table 2 Multivariate Cox regression analysis The KaplanCMeier method was used to estimate the survival probabilities over time. Results showed estimated 4-year survival of 83% of BRCA2 carriers compared to 37% of BRCA1 carriers and 12% of non-carriers (Table 3 and Fig. 1). There was a statistically significant difference between BRCA2 carriers and non-carriers (= 0.013), however no statistically significant survival differences were seen for BRCA1 carriers when compared with both BRCA2 carriers (= 0.355) and non-carriers (= 0.174). The KaplanCMeier curve was also plotted using 95% Hall-Wellner confidence bands for survivorship (Fig. 2). Fig. 1 KaplanCMeier estimates of survival by BRCA1 carriers vs. BRCA2 carriers vs. non-carriers Fig. 2 Ninety-five percent Hall-Wellner confidence bands for survivorship Table 3 Survival by BRCA1 carriers vs. BRCA2 carriers vs. non-carriers (%) Discussion Our study represents the first report of a population-based sample of incident epithelial ovarian cancer cases stratified by BRCA status, suggesting greater generalizability of our results. Furthermore, all previously published studies reporting a survival advantage in BRCA carriers [29, 33C36, 48] have been based predominantly on advanced stage cases, whereas our study is the first with a stage distribution comparable to that seen in the general population, thus enhancing relevance to all women with BRCA-associated ovarian cancer. Moreover, the two previously published studies that reported no survival difference between BRCA carriers and non-carriers [38, 39] examined cases without stratifying for stage, which is currently the strongest prognostic variable in invasive epithelial ovarian cancer. Among the few previous studies reporting a survival advantage were those based on specific population groups, including three studies in Ashkenazi Jewish women [29, 34, 35], and one study in Japanese women [33], limiting generalizability of the results to the US population. Two of the previous studies reporting a survival advantage investigated BRCA1 mutations only [33, 37], and found a survival advantage in BRCA1 carriers compared to sporadic cases, contrary to the findings of the current study. The study by Buller et al..