Age at first pregnancy, adult weight gain, and postmenopausal breast cancer risk in the PROCAS Study cohort

Adult weight gain (AWG) increases postmenopausal breast cancer (BC) risk, whereas an early first pregnancy (FP) is protective. As pregnancy is a key contributor to weight gain, analysis of prospective data from 48,417 women in the Predicting Risk of Breast Cancer at Screening (PROCAS) cohort investigated a potential interaction effect between these two factors on BC risk. After a median follow-up of 6.4 years, 1702 incident breast cancers were identified. Compared to women with an early FP (< 30 years) and stable weight (≤ 5%), risk was highest among those with substantial AWG (> 30%) combined with a late FP (HR 2.48; 95% CI 1.82-3.37) or nulliparity (2.38; 1.74-3.27). Elevated risk was observed even with moderate weight gain (5-15%). A non-significant positive trend toward an additive interaction was observed for late FP (RERI 0.32), whereas the risk in nulliparous women appeared independent of weight gain (RERI -0.05). The authors conclude that maintaining a stable adult weight and an early FP are independently associated with a lower breast cancer risk, whereas adult weight gain remains a significant risk factor regardless of reproductive history (graphical abstract).