Racial disparities in molecular subtypes of endometrial cancer

Objectives: Racial differences in the molecular subtypes of endometrial cancer and associations with progression-free survival (PFS) were evaluated. Methods: Molecular, clinical and PFS data were acquired from the Cancer Genome Atlas (TCGA) including classification into the integrative, somatic copy number alteration and transcript-based subtypes. The prevalence and prognostic value of the aggressive molecular subtypes (copy number variant [CNV]-high, cluster 4 or mitotic) were evaluated in Black and White patients. Results: There were 337 patients including 14% self-designated as Black, 27% with advanced stage, and 82% with endometrioid histology. The CNV-high subtype was more common in Black than White patients (61.9% vs. 23.5%, P = 0.0005) and suggested worse PFS in Black patients (hazard ratio [HR] = 3.4, P = 0.189). The cluster 4 subtype was more prevalent in Black patients (56.8% vs. 20.9%, P < 0.0001) and associated with worse PFS in Black patients (HR = 3.4, P = 0.049). The mitotic subtype was more abundant in Black patients (64.1% vs. 33.7%, P = 0.002), indicated worse PFS in Black patients (HR = 4.1, P = 0.044) including the endometrioid histology (HR = 6.1, P = 0.024) and exhibited race-associated enrichment in cell cycle signaling and pathways in cancer including PLK1 and BIRC7. All of these aggressive molecular subtypes also indicated worse PFS in White patients, with unique enrichments in mitotic signaling different from Black patients. Conclusions: The aggressive molecular subtypes from TCGA were more common in Black endometrial cancer patients and indicated worse PFS in both Black and White patients. The mitotic subtypes also indicated worse PFS in Black patients with endometrioid histology. Enrichment patterns in mitotic signaling may represent therapeutic opportunities.