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Purpose: Early age at breast development (thelarche) has been associated with increased breast cancer risk. Average age at thelarche has declined over time, but there are few established risk factors for early thelarche. We examined associations between pre- and postnatal exposures and age at thelarche in a U.S. cohort of women born between 1928 and 1974. Methods: Breast cancer-free women ages 35–74 years who had a sister diagnosed with breast cancer were enrolled in the Sister Study from 2003–2009 (N = 50,884). At enrollment, participants reported their age at thelarche, which we categorized as early (≤10 years), average (11–13 years), and late (≥14 years), as well as information on early-life exposures. We estimated odds ratios (ORs) and 95% confidence intervals (CIs) for early and late thelarche relative to average age at thelarche using polytomous logistic regression for each early-life exposure, adjusted for birth cohort, race/ethnicity and family income level in childhood. We examined modification by birth cohort, race/ethnicity, family income, relative weight at age 10, and extent of breast cancer family history through stratification. Results: Early thelarche was more common in recent birth cohorts and among non-Hispanic Black and Hispanic women. Early thelarche (≤10 years) was associated with multiple prenatal exposures: gestational hypertensive disorder (OR = 1.25, 95% CI, 1.09–1.43), maternal diethylstilbestrol (DES) use (OR = 1.23, 95% CI, 1.04–1.45), maternal smoking during pregnancy (OR = 1.20, 95% CI, 1.13–1.27), and young maternal age (OR 1.30, 95% CI, 1.16–1.47 for &amp;lt;20 vs 25–29 years). Being firstborn was also associated with early thelarche (OR = 1.25, 95% CI, 1.17–1.33). Low birthweight (&amp;lt;2500 vs 2500–3999g) was suggestively associated with both early (OR = 1.06, 95% CI, 0.96–1.17) and late (OR = 1.15, 95% CI, 1.05–1.25) thelarche, as was use of soy formula in infancy (Early: OR = 1.10, 95% CI, 0.93–1.30; Late: OR = 1.07, 95% CI, 0.92–1.25). Patterns were generally similar across strata of modifiers of interest. Conclusion: Associations between pre- and postnatal exposures and age at thelarche suggest that the early-life environment may influence breast development and therefore may also affect breast cancer risk by altering the timing of pubertal breast development.

Early-life Exposures and Age at Breast Development in the Sister Study Cohort