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

Research output: Contribution to journalArticle

  • 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
Original languageEnglish
Pages (from-to)1500-1508
Number of pages9
JournalCancer Epidemiology, Biomarkers and Prevention
Volume27
Issue number12
Early online date18 Sep 2018
DOIs
DateAccepted/In press - 7 Sep 2018
DateE-pub ahead of print - 18 Sep 2018
DatePublished (current) - 1 Dec 2018

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.

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    Rights statement: This is the accepted author manuscript (AAM). The final published version (version of record) is available online via AACR Publications at https://doi.org/10.1158/1055-9965.EPI-18-0036 . Please refer to any applicable terms of use of the publisher.

    Accepted author manuscript, 372 KB, PDF document

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