Associations of reproductive time events and intervals with breast cancer risk: a report from the Shanghai Breast Cancer Study.

While there is clear evidence for an association between later age at first live birth and increased breast cancer risk, associations with the timing of other reproductive events are less clear. As breast tissues undergo major structural and cellular changes during pregnancy, we examined associations between reproductive time events and intervals with breast cancer risk among parous women from the population-based Shanghai Breast Cancer Study (SBCS). Unconditional logistic regression was used to evaluate associations with breast cancer risk for 3,269 cases and 3,341 controls. In addition to later age at first live birth, later ages at first pregnancy and last pregnancy were significantly associated with increased breast cancer risk (p-trend = 0.002, 0.015, 0.008, respectively); longer intervals from menarche to first or last live birth were also associated with increased risk (p-trend < 0.001, =0.018, respectively). Analyses stratified by menopausal status and estrogen receptor (ER)/progesterone receptor (PR) status revealed that associations for later age at first pregnancy or live birth and longer intervals from menarche to first or last live birth occurred among premenopausal women and ER+/PR+ breast cancers, whereas the association for later age at last pregnancy occurred among postmenopausal women and women with ER+/PR- or ER-/PR+ breast cancers. Because of the high correlation with other reproductive variables, models did not include adjustment for age at first live birth; when included, the significance of all associations was attenuated. These findings suggest that while reproductive time events and intervals play an important role in breast cancer etiology, contributions may differ by menopausal status and hormone receptor status of breast cancers.