Allostatic Load in Endometrial Cancer Disparities

Endometrial cancer incidence and mortality are increasing, particularly among Black women and for aggressive subtypes. Allostatic load (AL), a composite measure of physiologic dysregulation across metabolic, cardiovascular, and immune systems, varies by racial category and tumor subtype in other cancers. Endometrial cancer is strongly associated with obesity, and it is unknown whether AL scores maintain sufficient heterogeneity to evaluate differences across subgroups or with clinical outcomes.

To describe the performance of AL scoring in endometrial cancer patients and examine associations with tumor characteristics (grade/histology) and survival outcomes.

We evaluated AL among 398 participants newly diagnosed with endometrial cancer. AL score was calculated by assigning 1 point for each "high-risk" value (by clinical reference range or distribution-based) for 15 biologic variables for vital signs, anthropometrics, blood-based biomarkers, and medical comorbidities.

Distribution-based thresholds for variables were used to preserve heterogeneity in this obesity-dominant context. Overall, 68.7% of Black women had high AL compared to White (56.7%), Hispanic (56.7%), and other race (32.3%) women. Decision tree analyses revealed grade-dependent associations between AL and survival. For women with low-grade tumors, higher AL was associated with poorer overall survival. For high-grade tumors, intermediate AL (≥4, <8) were associated with shortest overall survival. Black women with low-grade disease experienced shorter progression-free survival regardless of AL.

AL scoring maintains heterogeneity despite high obesity prevalence in endometrial cancer. Varying relationships between AL and survival by tumor grade and ethnoracial group suggest cumulative physiologic burden and social/structural factors may jointly shape endometrial cancer disparities.