Circulating Growth and Sex Hormone Levels and Breast Tissue Composition in Young Nulliparous Women.

Abstract

BACKGROUND: Endogenous hormones are associated with breast cancer risk, but little is known about their role on breast tissue composition, a strong risk predictor. This study aims to investigate the relationship between growth and sex hormone levels and breast tissue composition in young nulliparous women. METHODS: A cross-sectional study of 415 young (age ∼21.5 years) nulliparous women from an English prebirth cohort underwent a MRI examination of their breasts to estimate percent-water (a proxy for mammographic percent density) and provided a blood sample to measure plasma levels of growth factors (insulin-like growth factor-I, insulin-like growth factor-II, insulin growth factor-binding protein-3, growth hormone) and, if not on hormonal contraception (n = 117) sex hormones (dehydroepiandrosterone, androstenedione, testosterone, estrone, estadiol, sex hormone-binding globulin, prolactin). Testosterone (n = 330) and sex hormone-binding globulin (n = 318) were also measured at age 15.5 years. Regression models were used to estimate the relative difference (RD) in percent-water associated with one SD increment in hormone levels. RESULTS: Estradiol at age 21.5 and sex hormone-binding globulin at age 21.5 were positively associated with body mass index (BMI)-adjusted percent-water [RD (95% confidence interval (CI)): 3% (0%-7%) and 3% (1%-5%), respectively]. There was a positive nonlinear association between androstenedione at age 21.5 and percent-water. Insulin-like growth factor-I and growth hormone at age 21.5 were also positively associated with BMI-adjusted percent-water [RD (95% CI): 2% (0%-4%) and 4% (1%-7%), respectively]. CONCLUSIONS: The findings suggest that endogenous hormones affect breast tissue composition in young nulliparous women. IMPACT: The well-established associations of childhood growth and development with breast cancer risk may be partly mediated by the role of endogenous hormones on breast tissue composition.