Abstract PS5-10-22: Allostatic Load and Risk of Obesity Related and Total Cancer in Postmenopausal Women

Abstract Allostatic Load and Risk of Obesity-Related and Total Cancer in Postmenopausal Women: Insights from the Women’s Health InitiativeBackground: Allostatic load (AL), a composite biomarker of physiological stress, has been associated with chronic disease, but its relationship with cancer—particularly obesity-related cancers—remains understudied in large, diverse populations. In this analysis, we investigated the association between baseline AL and the incidence of obesity-related cancers and total cancer risk, among postmenopausal women in the Women’s Health Initiative (WHI). Methods: Among 161,805 WHI participants, we identified a final cohort of 28,102 women with information on AL after excluding individuals with delayed biomarker collection, or prior cancer diagnosis. AL was calculated using eight biomarkers (pulse, systolic and diastolic blood pressure, body mass index (BMI), waist circumference, C-reactive protein (CRP), fasting glucose, and total cholesterol). Participants were stratified into tertiles of AL (low: 0–2, medium: 3–5, and high: 6–8). Cox proportional hazards and Fine-Gray models were used to assess associations between AL and incident cancers, separately looking at the risk of 13 obesity related cancers and total cancer risk, and adjusting for sociodemographic, behavioral, and reproductive factors. Results: Over median follow up of 18. 64 years, 14.1% of participants developed obesity-related cancers and 22.3% developed any cancer. In fully adjusted models, women in the highest AL tertile at WHI enrollment had significantly elevated risk of obesity-related cancer compared to the lowest tertile (HR 1.20; 95% CI: 1.01–1.42; p=0.044). A 1-point increase in AL score was associated with a 4% higher risk (HR 1.04; 95% CI: 1.00–1.07; p=0.028). Total cancer risk did not increase significantly with higher AL score (HR for high vs. low: 1.07; 95% CI: 0.92–1.24; p=0.388; per point: HR 1.02; 95% CI: 1.00–1.05; p=0.079). These associations did not differ significantly by race, ethnicity or income. Conclusions: Elevated allostatic load is independently associated with increased risk of obesity-related cancer among postmenopausal women in the WHI. These findings highlight the potential role of cumulative physiological stress in in cancer risk beyond obesity alone and suggest that AL may be a valuable biomarker incorporating social and metabolic stressors for cancer risk stratification in older women. Citation Format: J. Chi, F. Wang, Y. Zong, M. Pennell, M. Yu, V. Nair, A. Vasbinder, D. Lane, A. Shadyab, C. Valencia, N. Saquib, J. Wactawski-Wende, P. Richey, M. Skiba, M. Simon. Allostatic Load and Risk of Obesity Related and Total Cancer in Postmenopausal Women abstract. In: Proceedings of the San Antonio Breast Cancer Symposium 2025; 2025 Dec 9-12; San Antonio, TX. Philadelphia (PA): AACR; Clin Cancer Res 2026;32(4 Suppl):Abstract nr PS5-10-22.