Physical Activity From Menarche-to-first Pregnancy And Risk Of Breast Cancer: The California Teachers Study

Abstract

PURPOSE: Physical activity (PA) is associated with decreased breast cancer (BCa) risk. A longer menarche-to-first pregnancy window of susceptibility (WOS) is associated with increased BCa risk. Whether PA during the menarche-to-first pregnancy WOS offsets BCa risk is unclear. It is also unknown if differences in risk exist by BCa subtype. METHODS: We examined the prospective association between PA during the menarche-to-first pregnancy WOS and BCa risk in the California Teachers Study (N=78,940). Recreational PA levels from high school to current age, or, age 55, were recalled at cohort entry and converted to metabolic equivalent of task hours per week (MET-h/wk). We used multivariable Cox proportional hazards models to estimate hazard ratios (HRs) and 95% confidence intervals (CIs) of incident invasive BCa for WOS and PA. RESULTS: 5,157 invasive BCa cases developed. The median length of follow-up was 21.6 years. Longer menarche-to-first pregnancy WOS (≥20 vs. <15 years) was associated with increased BCa risk (HR=1.23, 95% CI=1.13-1.34). Women with higher PA during menarche-to-first pregnancy WOS had decreased risk of invasive BCa (≥40 vs. <9 MET-h/wk: HR=0.89, 95% CI=0.83-0.97). The inverse association between PA during the menarche-to-first pregnancy WOS and BCa risk was strongest in triple-negative BCa (TNBC: ≥40 vs. <9 MET-h/wk: HR=0.53, 95% CI=0.32-0.87; luminal A-like: ≥40 vs. <9 MET-h/wk: HR=0.92, 95% CI=0.80-1.06; luminal B-like: ≥40 vs. <9 MET-h/wk: HR=0.84, 95% CI=0.52-1.36). Higher PA level during the menarche-to-first pregnancy WOS was associated with decreased BCa risk only among women with moderate (15-19 years) menarche-to-first pregnancy intervals (≥40 vs. <9 MET-h/wk: HR=0.80, 95% CI=0.69-0.92), but not women with short (<15 years; ≥40 vs. <9 MET-h/wk: HR=0.96, 95% CI=0.86-1,06) or long (≥20 years; ≥40 vs. <9 MET-h/wk: HR=0.93, 95% CI=0.74-1.17) intervals. CONCLUSION: PA during the menarche-to-first pregnancy WOS was associated with lower BCa risk in our cohort. Understanding the timing of PA over the life course in relationship to non-modifiable reproductive risk factors such as pregnancy maybe particularly important. Supported by NIH Grant U01 CA199277; P30 CA033572; P30 CA023100; UM1 CA164917; R01-CA077398; U54 CA155850; UL1 TR002014; UL1 TR000003; and KL2 TR002015.