Impact of Childbearing and Breastfeeding on Breast Density Change, and Subsequent Breast Cancer Risk in Postmenopausal Women: A Mediation Analysis.
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We examined the associations of parity and breastfeeding with postmenopausal breast density, longitudinal changes in breast density, and breast cancer risk, and assessed the extent to which breast density mediates these relationships. We analyzed a cohort of women who underwent mammography in 2009-2010 and had at least one follow-up mammogram through 2016. Parity and breastfeeding history were self-reported, breast density was classified using Breast Imaging Reporting and Data System (BI-RADS), and relative risks (RRs) were estimated using Poisson regression. Mediation analysis evaluated the contributions of baseline breast density and its longitudinal change. Lower parity and shorter breastfeeding duration were associated with higher baseline breast density and less favorable density trajectories over time, including a greater likelihood of increasing density and a lower likelihood of decreasing density. Compared with women with at least two children who breastfed for > 12 months, women with one child who did not breastfeed had a higher breast cancer risk (RR: 1.53; 95% confidence interval [CI]: 1.43-1.64), with a clear dose-response pattern across parity and breastfeeding categories. Parity showed stronger associations than breastfeeding duration with both breast density and breast cancer risk, and these associations were generally stronger among women aged 65 years or older. Baseline breast density and its longitudinal change mediated approximately 10%-15% of the associations between reproductive factors and breast cancer risk. These findings suggest that reproductive history has long-term effects on breast tissue composition and partly explains subsequent breast cancer risk in postmenopausal women.