Introduction: Although reproductive factors have been known for decades to be associated with breast cancer risk, it is unclear to what extent these associations differ by estrogen and progesterone receptor (ER/PR) status. This report presents the first meta-analysis of results from epidemiological studies that have investigated parity, age at first birth, breastfeeding, and age at menarche in relation to ER+PR+ and ER-PR- cancer risk.
Materials and methods: We calculated summary relative risks (RRs) and corresponding 95% confidence intervals (CIs) using a fixed effects model.
Results: Each birth reduced the risk of ER+PR+ cancer by 11% (RR per birth = 0.89, 95% CI = 0.84-0.94), and women who were in the highest age at first birth category had, on average, 27% higher risk of ER+PR+ cancer compared with women who were in the youngest age at first birth category (RR = 1.27, 95% CI = 1.07-1.50). Neither parity nor age at first birth was associated with the risk of ER-PR- cancer (RR per birth = 0.99, 95% CI = 0.94-1.05; RR of oldest versus youngest age at first birth category = 1.01, 95% CI = 0.85-1.20). Breastfeeding and late age at menarche decreased the risk of both receptor subtypes of breast cancer. The protective effect of late age at menarche was statistically significantly greater for ER+PR+ than ER-PR- cancer (RR = 0.72 for ER+PR+ cancer; RR = 0.84 for ER-PR- cancer, p for homogeneity = 0.006).
Conclusion: Our findings suggest that breastfeeding (and age at menarche) may act through different hormonal mechanisms than do parity and age at first birth.