BRCA1/2 mutations and survival of high-grade endometrioid endometrial cancer

Abstract

BackgroundBRCA1/2 mutations have been shown to be associated with the development of many solid tumors including endometrial cancer (EC). The objectives of this study are to analyze the association between BRCA1/2 mutational status and clinicopathological characteristics as well as outcomes in EC patients. Methods510 eligible EC patients from the Cancer Genome Atlas database were included in the study. The association between clinicopathological characteristics and different BRCA1/2 mutational status was compared and analyzed. Analyses of the impact of BRCA mutations on survival in EC patients was conducted using Kaplan-Meier survival analyses and Cox regressions. In order to control confounding bias between groups, propensity score matching method was used. ResultsAmong the eligible patients, 11 (2.2%) harbored BRCA1 mutation, 43 (8.4%) harbored BRCA2 mutation, and 36 (7.1%) harbored both. Body mass index, rates of hypertension history, proportion of non-endometrioid histology and rates of positive peritoneal cytology were lower in patients with BRCA1/2 mutations compared with the group of wild-type counterpart (p = 0.020, 0.048, 0.001 and 0.012, respectively). Patients with BRCA1/2 mutations showed longer overall (OS) and recurrence-free survival (RFS) (in Kaplan-Meier analyses, p < 0.001 and p = 0.004, respectively; in Cox regressions, p = 0.001 and 0.007, respectively). Further analyses showed that the impact of BRCA mutations on survival was significant only in patients with high-grade endometrioid EC. Based on the cohorts generated after propensity score matching, in high-grade endometrioid EC patients, the influence of BRCA1/2 mutations remained significant on OS, but not on RFS (p = 0.003 and 0.057 in Kaplan-Meier analyses, p = 0.020 and 0.071 in Cox regressions). ConclusionBRCA1/2 mutations are associated with better survival in patients with high grade endometrioid EC, indicating the value of BRCA testing in EC clinical management.