Abstract 3630: Physical activity, smoking and breast cancer risk: A prospective cohort study in the UK biobank

Abstract Background: Physical activity and smoking are modifiable breast cancer risk factors that operate through partially shared biological pathways, such as hormone regulation and inflammation. However, their potential interactions, especially across menopausal groups, remain largely unexplored. This study aimed to assess whether smoking status modifies the association between physical activity and breast cancer risk. Methods: Females ≥40 years without prior cancer in the UK Biobank (2007-2010) provided self-reported lifestyle factors. Physical activity was categorized using metabolic equivalent hours per week (MET-hrs/week): high (≥50), moderate (10-50), and low (<10). Incident cancers were ascertained through May 2022. Interaction between physical activity and smoking status (never, past, current) was evaluated using Cox proportional hazards models with product terms. Multivariable models were adjusted for anthropometrics, reproductive, lifestyle, socioeconomic and screening factors. Results: Among 242 721 participants followed for a mean of 12.53 years (SD: 2.55), 773 premenopausal and 7989 postmenopausal breast cancer cases occurred. High physical activity was associated with lower risk of both premenopausal (HR=0.78, 95%CI: 0.62-0.97) and postmenopausal (HR=0.88, 95%CI: 0.83-0.94) breast cancer. Smoking status was not associated with premenopausal breast cancer risk (past smoker: HR=0.95, 95%CI:0.79-1.13; current: HR=0.89, 95%CI: 0.70-1.15) but was associated with a higher postmenopausal breast cancer risk (past smoker: HR=1.05, 95%CI:1.00-1.11; current: HR=1.13, 95%CI: 1.03-1.23). When evaluating the joint association between physical activity and smoking, current smoking appeard to attenuate the protective association of physical activity with both premenopausal (HR=1.61, 95%CI: 0.74-3.51) and postmenopausal (HR=1.29, 95%CI:1.02 to 1.62) breast cancer risk, although multiplicative interaction terms were not statistically significant. Conclusions: Smoking status was not independently associated with premenopausal but associated with higher postmenopausal breast cancer risk. Nevertheless, current smokers appeared to derive less protective benefits from physical activity than never smokers. These findings highlight the importance of evaluating joint lifestyle effects rather than single exposure alone in breast cancer prevention. Citation Format: Hannach Harsanyi, Andrew Harper, Heinz Freisling, Sasha Lupichuk, Adetunji T. Toriola, Lin Yang. Physical activity, smoking and breast cancer risk: A prospective cohort study in the UK biobank [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2026; Part 1 (Regular Abstracts); 2026 Apr 17-22; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2026;86(7 Suppl):Abstract nr 3630.