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 (aged ~21.5 years) nulliparous women from an English pre-birth cohort underwent a magnetic resonance imaging 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 standard deviation increment in hormone levels. RESULTS: Estradiol at age 21.5 and sex-hormone-binding-globulin at ages 21.5 were positively associated with body mass index (BMI)-adjusted percent-water (RD (95% CI): 3% (0%, 7%) and 3% (1%, 5%), respectively). There was a positive non-linear 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.