Breast cancer risk among postmenopausal women: Exploring existing interactions between BMI and reproductive factors (Fertile Years) in the Malmö Diet and Cancer Study

Introduction: Breast cancer remains a global public health priority, with increasing incidence and mortality among postmenopausal women. While high body mass index (BMI) and reproductive history are established risk factors, the interaction between BMI and cumulative reproductive exposure, measured as fertile years, has not been thoroughly investigated. This study investigated the independent and interactive effects of BMI and fertile years on postmenopausal breast cancer risk. Methods: Data from 6,628 postmenopausal women enrolled in the Malmö Diet and Cancer Study were analysed. BMI (kg/m²) was measured at baseline, and fertile years were estimated by subtracting the duration of pregnancy, breastfeeding, and miscarriage from the interval between menarche and menopause. Cox proportional hazards models estimated hazard ratios (HRs) for breast cancer risk. Interaction effects were evaluated on both multiplicative and additive scales using indices such as Relative Excess Risk due to Interaction (RERI), Attributable Proportion (AP), and Synergy Index (SI). Results: Over approximately 29,000 person-years of follow-up, 625 breast cancer cases were identified (9.4%), yielding an incidence rate of 3.3 per 1,000 person-years. Independent associations between higher BMI and longer fertile years with breast cancer were observed, but not statistically significant. No significant multiplicative interaction was detected. However, a statistically significant additive interaction was found: RERI = 0.86 (95% CI: 0.14–1.58, p = 0.018) and AP = 0.39 (95% CI: 0.13–0.66, p = 0.003), indicating that 39% of the joint effect could be attributed to interaction. Conclusion: This study provides novel evidence of a significant additive interaction between BMI and fertile years in postmenopausal breast cancer risk. These findings highlight the importance of assessing BMI and fertile years jointly in breast cancer risk evaluation. Future studies should explore underlying biological mechanisms and validate these results in diverse populations to inform targeted prevention strategies and improve the treatment options.