Circulating growth and sex hormone levels and breast tissue composition in young nulliparous women

Rachel Denholm, Bianca L. De Stavola, John H. Hipwell, Simon J. Doran, Jeff M.P. Holly, Elizabeth Folkerd, Mitch Dowsett, Martin O. Leach, David J. Hawkes, Isabel Dos-Santos-Silva*

*Corresponding author for this work

Research output: Contribution to journalArticle (Academic Journal)peer-review

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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.

Original languageEnglish
Pages (from-to)1500-1508
Number of pages9
JournalCancer Epidemiology, Biomarkers and Prevention
Issue number12
Early online date18 Sep 2018
Publication statusPublished - 1 Dec 2018

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