PURPOSE: This study sought to describe the physical activity-endometrial cancer association and potential mediation of this relationship by obesity in midlife. METHODS: Participants were 67,705 women (aged 50–71 years) enrolled in the NIH-AARP cohort who reported their historical leisure-time physical activity patterns starting at age 15–18 years. We identified five long-term physical activity patterns between adolescence and cohort entry (i.e., inactive, maintained-low, maintained-high, increasers, decreasers). We used Cox regression (Hazard ratio - HR [95% CI]) to assess the relationship between these patterns and midlife obesity and endometrial cancer, adjusting for covariates. Mediation analysis was used to decompose the physical activity patterns-endometrial cancer association to estimate the proportion of the physical activity-endometrial cancer association mediated by midlife obesity. RESULTS: During an average 12.3 years of follow-up 1,468 endometrial cancers occurred. Long-term physical activity patterns were inactive, maintained-low, maintained-high, increasers, and decreasers. Compared to long- term inactive women, women who maintained-high or increased activity levels had a 19–26% lower risk for endometrial cancer (maintained-high: HR = 0.81 [0.67, 0.98]; increasers: HR = 0.74 [0.61, 0.91]). They also had a 45–77% lower risk for obesity in midlife (e.g., maintained-high, BMI 30–39.9: HR = 0.50 [0.46, 0.55]; maintained- high, BMI 40+: HR = 0.32 [0.26, 0.39]). Obesity was a significant mediator and appeared to account for 55–63% of the physical activity-endometrial cancer associations observed. CONCLUSIONS: Both initiating and maintaining physical activity throughout adulthood can play a role in preventing obesity and in turn, lowering the risk for endometrial cancer.

The following are the 23 highest scoring abstracts of those submitted for presentation at the 45th Annual ASPO meeting held virtually March 29 – April 1, 2021.