Early-life exposures and age at thelarche in the Sister Study cohort

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 US cohort of women born between 1928 and 1974.

Breast cancer-free women ages 35-74 years who had a sister diagnosed with breast cancer were enrolled in the Sister Study from 2003 to 2009 (N = 50,884). At enrollment, participants reported information on early-life exposures and age at thelarche, which we categorized as early (≤ 10 years), average (11-13 years), and late (≥ 14 years). For each exposure, we estimated odds ratios (ORs) and 95% confidence intervals (CIs) for early and late thelarche using polytomous logistic regression, adjusted for birth cohort, race/ethnicity and family income level in childhood.

Early thelarche was associated with multiple prenatal exposures: gestational hypertensive disorder (OR = 1.25, 95% CI 1.09-1.43), diethylstilbestrol use (OR = 1.23, 95% CI 1.04-1.45), smoking during pregnancy (OR = 1.20, 95% CI 1.13-1.27), young maternal age (OR 1.30, 95% CI 1.16-1.47 for < 20 vs. 25-29 years), and being firstborn (OR = 1.25, 95% CI 1.17-1.33). Birthweight < 2500 g and soy formula use in infancy were positively associated with both early and late thelarche.

Associations between pre- and postnatal exposures and age at thelarche suggest that the early-life environment influences breast development and therefore may also affect breast cancer risk by altering the timing of pubertal breast development.