Maternal and prenatal factors and age at thelarche in the LEGACY Girls Study cohort: Implications for breast cancer risk

Abstract

Background: Earlier onset of breast development (thelarche) is associated with increased breast cancer risk. Identifying modifiable factors associated with earlier thelarche may provide an opportunity for breast cancer risk reduction starting early in life, which could especially benefit girls with a greater absolute risk of breast cancer due to family history. Methods: We assessed associations of maternal pre-pregnancy body mass index (BMI), physical activity during pregnancy, gestational weight gain and daughters' weight and length at birth with age at thelarche using longitudinal Weibull models in 1031 girls in the Lessons in Epidemiology and Genetics of Adult Cancer from Youth (LEGACY) Girls Study - a prospective cohort of girls, half of whom have a breast cancer family history (BCFH). Results: Girls whose mothers had a pre-pregnancy BMI of ≥25 and gained ≥30 lbs were 57% more likely to experience earlier thelarche than girls whose mothers had a pre-pregnancy BMI of <25 and gained <30 lbs [hazard ratio (HR) = 1.57, 95% CI: 1.16, 2.12]. This association was not mediated by childhood BMI and was similar in girls with and without a BCFH (BCFH: HR = 1.41, 95% CI: 0.87, 2.27; No BCFH: HR = 1.62, 95% CI: 1.10, 2.40). Daughters of women who reported no recreational physical activity during pregnancy were more likely to experience earlier thelarche compared with daughters of physically active women. Birthweight and birth length were not associated with thelarche. Conclusion: Earlier thelarche, a breast cancer risk factor, was associated with three potentially modifiable maternal risk factors - pre-pregnancy BMI, gestational weight gain and physical inactivity - in a cohort of girls enriched for BCFH.