Background
Pre?diagnosis physical activity is associated with improved breast cancer survival, but the shape of the hazard reduction over time remains inadequately characterized. Most prior studies have relied on Cox proportional hazards models, which assume constant hazard ratios, an assumption with decreased plausibility over long?term follow?up where causes of death evolve.
Objectives
To estimate time?varying hazard ratios (HRs) by menopausal status for the association between pre?diagnosis moderate?to?vigorous physical activity (MVPA) at recommended levels for the general population and overall survival in a sample of Mexican women diagnosed with breast cancer.
Methods
We included 977 women (52.9% postmenopausal) diagnosed with breast cancer (2004–2007) from the multicenter CAMA study in three Mexican regions, with vital status follow?up through December 2024. Pre?diagnosis leisure?time MVPA was assessed via a validated interview and dichotomized at ≥150 minutes/week. Time?varying hazard ratios were derived from accelerated failure time (AFT) models. The log?normal distribution was selected as optimal via Akaike Information Criterion and graphical diagnostics. For each menopausal stratum, we computed instantaneous hazard functions for MVPA ≥150 and <150 min/week from the AFT parameters, with other covariates fixed at reference values; HRs over time were estimated from the ratio of these functions. Uncertainty was quantified via bootstrap resampling within 40 multiply?imputed datasets. Models were adjusted for DAG?derived confounders: age, education, residence, healthcare access, alcohol, smoking, Dietary Inflammatory Index, comorbidity, and clinical stage.
Results
Over a median follow?up of 18.3 years, 422 deaths (43.2%) occurred. Among postmenopausal women, meeting MVPA guidelines was associated with a time?varying protective effect. The hazard ratio (≥150 vs. <150 min/week) was 0.38 (95% CI: 0.17–0.60) at 1?year post?diagnosis, 0.55 (0.35–0.74) at 5 years, 0.61 (0.44–0.79) at 10 years, 0.65 (0.48–0.81) at 15 years, and 0.67 (0.52–0.83) at 20 years (Figure, Panel B). Among premenopausal women, hazard ratios were near unity across all time points (Figure, Panel A).
Conclusions
Pre?diagnosis attainment of physical activity guidelines is associated with a significant survival advantage for women subsequently diagnosed with breast cancer, particularly postmenopausal women. This benefit manifests as a time?varying hazard reduction, strongest during the early, highest?risk survivorship interval and remains significant 20 years after diagnosis. This pattern suggests cancer?specific mechanisms are prominent over reductions of CVD or metabolic mortality occurring at later intervals. Even if guideline?level activity does not prevent breast cancer in all women, it may substantially improve survival outcomes for those who are diagnosed.

Figure. Time?Varying Hazard Ratios for Pre?Diagnosis Physical Activity (?150 vs. <150 min/week) and Overall survival after Breast Cancer Diagnosis from the CAMA study (Mexico). (A) Premenopausal women. (B) Postmenopausal women. Solid lines represent poole