Racial disparities in endometrial cancer (EC) survival after molecular classification (MC).

5620 Background: Black (BAA) patients with EC have double the mortality rate compared to White patients. It is unclear if these survival differences persist after MC. Here, we examine racial disparities in this context and seek to identify molecular differences by race. Methods: EC samples (n = 10,162: BAA n=2,410, White n=7,752) were analyzed by NGS (NextSeq/NovaSeq) and RNA (NovaSeq) (Caris Life Sciences, Phx, AZ). Four well-described EC groups were created: POLE ultramutated (POLE-mt), MSI-H, TP53-mt, or No Specific Molecular Profile (NSMP; TP53-wt). Overall survival (OS) was obtained from insurance claims and calculated from tissue collection to last contact for MC cohorts. Hazard ratio (HR) was calculated by Cox proportional hazards, with p-value calculated by log-rank test. Race was self-reported. Results: There was a higher prevalence of BAA patients in the TP53-mt subtype (69.1% vs. 43%), compared with POLE-mt (1% vs. 2.26%) and NSMP (16.4% vs. 31%) (p<0.001). Across EC, BAA patients had shorter OS (29.8 vs 39.7 months (m); HR: 1.30 (1.22-1.39), p<0.001). BAA patients had worse OS in the NSMP cohort (36.8 vs 49.5m; HR 1.35 (1.15-1.59), p<0.001) and TP53-mt cohort (26.1 vs 29.6 m; HR 1.13 (1.05-1.22), p=0.002). Race was not associated with differences in OS in POLE-mt (NR vs was 51.4 m) and MSI-H (44.4 vs 45.9 m). There were molecular differences between race when stratified by MC (q<0.05) (Table 1). Gene set enrichment analysis showed downregulation of immune-related pathways in BAA. In NSMP tumors, BAA patients had lower IFNγ signature (0.72-fc) and worse post-pembrolizumab survival (16.9 vs 24.6 m; HR 1.46 (1.09-1.95), p=0.011). Conclusions: Previous studies demonstrated that racial disparities in endometrial cancer persist even when controlling for histology. This study demonstrates that these disparities persist even after controlling for MC, as defined by the ProMisE classification. BAA patients were more likely to develop TP53-mt tumors, but the survival disparity was largest in the NSMP group. Furthermore, Black and White patients exhibit differential expression of known prognostic mutations even within the same MC group. Molecular differences by race and subtype. Biomarker TP53-mt NSMP BAA % White % BAA % White % ARID1A -mt 4.47 10.3 32.8 48.9 CTNNB1 -mt NS NS 31.1 40.2 FGFR2 -mt 0.60 2.94 3.29 11.3 PIK3CA -mt 23.1 36.6 NS NS PIK3R1 -mt 9.58 15.4 17.9 35.0 PTEN -mt 6.83 15.7 40.4 66.9 PPP2R1A-mt 15.5 23.8 NS NS CDKN2A -del NS NS 22.0 13.7