Age at First Pregnancy, Adult Weight Gain and Postmenopausal Breast Cancer Risk: The PROCAS Study (United Kingdom).

Adult weight gain (AWG) increases postmenopausal breast cancer risk, whereas an early first pregnancy (FP) is protective. As pregnancy is a key contributor to weight gain, we investigated a potential interaction effect between these two factors on BC risk. We analysed prospective data from 48,417 women in the Predicting Risk of Breast Cancer at Screening (PROCAS) cohort (recruited 2009-2015). A Cox proportional hazards model was used to test for an interaction between first pregnancy age and weight gain on breast cancer 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 (≥ 30 years) (HR: 2.48, 95% CI: 1.82-3.37) or nulliparity (HR: 2.38, 95% CI: 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 (Relative Excess Risk due to Interaction (RERI): 0.32), whereas the risk in nulliparous women appeared independent of weight gain (RERI: -0.05). Maintaining a stable adult weight and an early first pregnancy are independently associated with a lower breast cancer risk. However, adult weight gain remains a significant risk factor regardless of reproductive history. The combination of high weight gain and late or no pregnancy identifies a high-risk group who could be prioritized for weight-management interventions in cancer prevention settings.