Purpose: A longer menarche-to-first pregnancy window of susceptibility (WOS) is associated with increased breast cancer risk. Whether physical activity, an established preventive risk factor, during the menarche-to-first pregnancy WOS offsets breast cancer risk overall or for specific molecular subtypes is unclear. Methods: We examined the prospective association between physical activity during the menarche-to-first pregnancy WOS and breast cancer risk in the California Teachers Study (N = 78,940). Recreational physical activity at multiple timepoints were recalled at cohort entry, and converted to metabolic equivalent of task hours per week (MET-hrs/wk). We used multivariable Cox proportional hazards models to estimate hazard ratios (HRs) and 95% confidence intervals (CIs). Results: We observed 5,157 invasive breast cancer cases over 21.6 years of follow-up. Longer menarche-to-first pregnancy WOS (≥ 20 vs. < 15 years) was associated with higher breast cancer risk (HR = 1.23, 95% CI = 1.13–1.34). Women with higher physical activity level during menarche-to-first pregnancy had lower risk of invasive breast cancer (≥ 40 vs. < 9 MET-hrs/wk: HR = 0.89, 95% CI = 0.83–0.97) and triple-negative subtype (≥ 40 vs. < 9 MET-hrs/wk: HR = 0.53, 95% CI = 0.32–0.87). No association was observed for luminal A-like and luminal B-like subtypes. Higher physical activity level was associated with lower breast cancer risk among women with moderate (15–19 years) menarche-to-first pregnancy intervals (≥ 40 vs. < 9 MET-hrs/wk: HR = 0.80, 95% CI = 0.69–0.92), but not with short (< 15 years) or long (≥ 20 years) intervals. Conclusion: Physical activity during a WOS was associated with lower breast cancer risk in our cohort. Understanding timing of physical activity throughout the life course in relationship with breast cancer risk maybe important for cancer prevention strategies.
- Window of susceptibility