Abstract
BackgroundEarly 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.MethodsBreast 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.ResultsEarly 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.ConclusionsAssociations 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.
Highlights
IntroductionAge at breast development (thelarche) has been associated with increased breast cancer risk
Age at breast development has been associated with increased breast cancer risk
We further examined whether associations between early-life exposures and age at thelarche were modified by other factors associated with early thelarche, including being born in a more recent birth cohort [6], African-American/Black or Hispanic/Latina identity [4], lower socioeconomic status [9], and increased familial risk of breast cancer [10]
Summary
Age at breast development (thelarche) has been associated with increased breast cancer risk. We examined associations between pre- and postnatal exposures and age at thelarche in a US cohort of women born between 1928 and 1974. Identifying modifiable risk factors associated with early thelarche may provide an opportunity for primary prevention of breast cancer by delaying the onset of pubertal breast development. A recent meta-analysis estimated that age at thelarche has declined at a rate of 3-months per decade over the past 50 years [6]. This rapid rate of decline suggests that environmental factors, acting independently or interacting with genetic susceptibility, are driving the secular trend [7]. Factors hypothesized to influence the timing of thelarche include nutritional factors, psychosocial stressors, and exposure to endocrine-disrupting chemicals, as well as conditions affecting the intrauterine environment [6,7,8].
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