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ABSTRACT Introduction Endometrial cancer (EC) mortality is rising, with increasing rates of advanced disease and high‐risk histologic subtypes. Allostatic load (AL), a biomarker of cumulative physiologic stress, has been linked to cancer‐associated outcomes. We evaluated the association between baseline AL and overall survival among patients with EC. Methods Patients diagnosed with EC at a single academic center were retrospectively identified. Baseline demographic, clinical, and laboratory values were used to calculate the primary exposure of interest, AL, based on ten physiologic biomarkers. A cohort‐defined threshold classified patients as having high versus low AL. Data were analyzed using unadjusted and adjusted models and Kaplan–Meier curves. Results A total of 2174 patients (mean age = 63.1 years, SD = 11.2) with EC were assessed for allostatic load at baseline, 69.2% met criteria for high AL ( n = 1505). The median follow up time was 49.5 months (IQR = 25.7, 76.4). High AL was associated with worse overall survival (unadjusted HR: 1.70 (95% CI, 1.28, 2.24), adjusted HR 1.58; 95% CI, 1.19, 2.11). Patients with high AL had a 52% higher rate of death compared to the low AL group. High AL was more prevalent among Black patients, those who were not married, and those without private insurance (all p < 0.001). Conclusions Elevated allostatic load was associated with worse overall survival in this cohort of patients with EC, consistent with the hypothesis that physiological stress may impact survival outcomes. These findings are hypothesis‐generating and suggest that physiologic stress and social disadvantage may contribute to survival differences warranting further study.
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