Background: Early age at first birth and multiparity reduce the risk of estrogen receptor-progesterone receptor (ERPR)-positive breast cancer, whereas breastfeeding reduces the risk of both ERPR-positive and ERPR-negative cancers. Methods: We used multivariable logistic regression analysis to investigate whether age at first birth (<25 or ≥25 years) and breastfeeding (ever/never) modify the long-term effect of parity on risk of ERPR-positive and ERPR-negative cancer using 1,457 incident breast cancer cases and 1,455 controls ages ≥55 years who participated in the Women's Contraceptive and Reproductive Experiences Study. Results: Women who gave birth before age 25 years had a 36% reduced risk of breast cancer compared with nulligravida that was not observed for women who started their families at an older age (P heterogeneity = 0.0007). This protective effect was restricted to ERPR-positive breast cancer (Pheterogeneity = 0.004). Late age at first birth increased the risk of ERPR-negative cancers. Additional births reduced the risk of ERPR-positive cancers among women with an early first birth (Ptrend = 0.0001) and among women who breastfed (Ptrend = 0.004) but not among older mothers or those who never breastfed. In women with a late first birth who never breastfed, multiparity was associated with increased risk of breast cancer. Conclusions: These findings suggest that the effect of parity on a woman's long-term risk of breast cancer is modified by age at first full-term pregnancy and possibly by breastfeeding.
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