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Insulin-like growth factor-1, growth hormone, and daily cycling estrogen are associated with mammographic density in premenopausal women

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Abstract

Background

Mammographic density represents epithelial and stromal proliferation, while insulin-like growth factor (IGF)-1, insulin-like growth factor-binding protein-3, growth hormone (GH), and estrogen may influence cellular proliferation. However, whether these growth factors independently, or in combination with estrogen, influence mammographic density in premenopausal women remains unclear.

Materials and methods

Growth factors were assessed in 202 ovulating premenopausal women participating in the Energy Balance and Breast Cancer Aspects-I study. Estrogen was assessed in serum, and daily in saliva, throughout a menstrual cycle. Computer-assisted mammographic density (Madena) was obtained from digitized mammograms (days 7–12 of the menstrual cycle). Associations between growth factors, estrogen, and mammographic density were studied in regression models.

Results

Women with a mean age of 30.7 years had a mean percent mammographic density of 29.8 %. Among women in the strata (above median split) of IGF-1 (>25 nmol/l) or GH (>0.80 mlU/l), we observed that an increase in salivary 17β-estradiol was associated with a higher odds for having higher percent mammographic density (>28.5 %). The odds ratios (ORs) per standard deviation increase in 17β-estradiol were 1.81 [95 % confidence interval (CI) 1.08–3.03] in the high IGF-1 stratum and 2.08 (95 % CI 1.10–3.94) in the high GH stratum. Furthermore, women in these strata of growth factors (above median) who had an overall average 17β-estradiol above median (>16.8 pmol/l) had higher ORs for having higher percent mammographic density (>28.5 %): IGF-1 4.13 (95 % CI 1.33–12.83) and GH 4.17 (95 % CI 1.41–12.28).

Conclusion

Growth factors, in combination with cycling estrogen, were associated with percent mammographic density, and may be of potential clinical relevance.

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Acknowledgments

We acknowledge each woman that participated in the EBBA-I study and give special thanks to Gunn Kristin Knudsen, Heidi Jakobsen, Anna-Kirsti Kvitnes, and Sissel Andersen for their professional assistance. We would also like to thank the Clinical Research Department, University Hospital of North Norway, Tromsø, for their skilled and always professional setting. This work was supported by the Norwegian Research Council (213997/H10), Foundation for the Norwegian Health and Rehabilitation Organization (59010-2000, 59010-2001, 59010-2002), and Norwegian Cancer Society (05087, TP 49,258).

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Authors and Affiliations

  1. Department of Oncology, Oslo University Hospital HF, Ullevål, 0424, Oslo, Norway

    Hanne Frydenberg, Vidar G. Flote, Sissi E. Finstad, Ellen Schlichting & Inger Thune

  2. Faculty of Health Sciences, UiT, The Arctic University of Norway, 9037, Tromsö, Norway

    Anita Iversen

  3. Department of Community Medicine, Faculty of Health Sciences, UiT, The Arctic University of Norway, Tromsö, Norway

    Anne-Sofie Furberg, Tom Wilsgaard & Inger Thune

  4. Hormone Laboratory, Oslo University Hospital, Aker, Norway

    Peter A. Torjesen

  5. Department of Human Evolutionary Biology, Harvard University, Cambridge, MA, USA

    Peter T. Ellison

  6. The Norwegian Cancer Registry, Oslo, Norway

    Giske Ursin

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  1. Hanne Frydenberg
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Frydenberg, H., Flote, V.G., Iversen, A. et al. Insulin-like growth factor-1, growth hormone, and daily cycling estrogen are associated with mammographic density in premenopausal women. Cancer Causes Control 25, 891–903 (2014). https://doi.org/10.1007/s10552-014-0389-z

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