Molecular characterization of endometrial carcinomas in Black and White patients reveals disparate drivers with therapeutic implications.

Although the incidence of endometrial carcinoma (EC) is similar in Black and White women, racial disparities are stark with the highest mortality rates observed among Black patients. Here, analysis of 1,882 prospectively sequenced ECs using a clinical FDA-authorized tumor-normal panel revealed a significantly higher prevalence of high-risk histologic and molecular EC subtypes in self-identified Black (n=259) compared to White (n=1,623) patients. Clinically actionable alterations, including high tumor mutational burden/ microsatellite-instability, which confer benefit from immunotherapy, were less frequent in ECs from Black than from White patients. Ultramutated POLE molecular subtype ECs associated with favorable outcomes were rare in Black patients. Results were confirmed by genetic ancestry analysis. CCNE1 gene amplification, which is associated with aggressive clinical behavior, was more prevalent in carcinosarcomas occurring in Black than in White patients. ECs from Black and White patients display important differences in their histologic types, molecular subtypes, driver genetic alterations and therapeutic targets.