Physical Activity in High-Risk Women reduces Breast Cancer Risk: UK Biobank Study

Purpose Physical activity (PA) is associated with reduced breast cancer (BC) risk in average-risk women. Its effect on genetically predisposed high-risk women remains unclear. Methods BC cases (n = 17,409) and controls (n = 26,907) were identified from the UK Biobank with BC-related Polygenic risk score (PRS) and/or pathogenic variants (PVs) in cancer susceptibility genes (CSG), International Physical Activity Questionnaire (IPAQ) data, and/or accelerometer-measured PA. Logistic regression was used to estimate odds ratios (ORs) for developing BC. PA and PRS were stratified into tertiles (low, moderate, high), and for carriers of BRCA1/BRCA2 and other high-penetrance CSG PVs. Results PA was associated with reduced BC risk. In the full cohort, high PA conferred a 25.8%–14.8% risk reduction by accelerometer and IPAQ, respectively. BC risk-reducing effect was maximal among women with moderate PRS (46.0%–23.7% reduction by accelerometer and IPAQ, respectively). BRCA1/BRCA2 PV carriers demonstrated 50.7% risk reduction (95% CI: 6.6–73.9%). No significant effect was observed among women with low PRS or among carriers of other CSG PVs. . Conclusion Both objectively and subjectively measured PA were associated with reduced BC risk among genetically predisposed women. These findings support PA as a feasible risk-reducing strategy for high-risk women.