Endometrial cancer survival disparities in women of African ancestry persist beyond clinical, molecular, and socioeconomic determinants

Abstract

IntroductionStark disparities in endometrial cancer (EC) risk and mortality exist between non-Hispanic Black and White women, with Black women experiencing higher incidence and worse survival. This disparity has been attributed to biological and socioeconomic factors, though how these factors interact to influence EC disparities remains unclear. This study modeled EC outcomes using race, area-level socioeconomic deprivation, clinical phenotypes, genetic ancestry, and molecular alterations. MethodsWe identified 281 cases of EC diagnosed from 2013-2023 in women who underwent clinical genomic sequencing as part of routine care across multiple Northwell Health sites. We estimated genetic ancestry, oncogenic alterations in 324 genes, microsatellite instability, and molecular classification. Geocoded patient addresses were used to derive the state-level Area Deprivation Index to estimate socioeconomic deprivation. ResultsAfrican ancestry patients were enriched for high-grade disease (89% vs 64%), serous histology (57% vs 26%), and the TP53-mutant molecular classification (71% vs 51%) compared to European ancestry patients (p-value<0.05). Socioeconomic deprivation quantiles were associated with race, with more deprived quantiles enriched for Black patients (p-value<0.001). Both race and genetic ancestry, but not area-level deprivation, were independently associated with differences in progression-free survival. TP53 mutations were enriched in African ancestry patients, while KRAS, PTEN, and ARID1A mutations were enriched in European ancestry patients (q<0.10). Cox proportional hazards modeling, adjusting for these factors, showed that African ancestry patients had worse progression-free survival (HR 1.91, p-value<0.05). ConclusionOur findings indicate that EC disparities persist after adjusting for socioeconomic, clinical, and molecular factors, highlighting the need to further investigate additional drivers of disparity. HighlightsO_LIThis study modeled drivers of mortality disparities in high-grade endometrial cancer. C_LIO_LISocioeconomic deprivation was associated with Black or African American race. C_LIO_LIAfrican ancestry was associated with serous, TP53-mutated, and higher-grade tumors. C_LIO_LIFeatures beyond state-level ADI and tumor phenotype may partly explain this gap. C_LI