Insulin, Insulin-like Growth Factor-1 and cycling estrogen predict premenopausal mammographic density.

Background: Mammographic density, a strong biomarker for breast cancer risk, represents epithelial and stromal proliferation. Insulin and insulin-like growth factor (IGF)-1 are suggested to influence cellular proliferation, while estrogen is a key factor in breast cancer development. However, whether the effects of these hormones among premenopausal women are mediated through mammographic density is less known. Material and Methods: Fasting serum insulin, IGF-1, and IGF binding protein (IGFBP)-3 were assessed among 202 healthy premenopausal women (Norwegian Energy Balance and Breast cancer Aspects study-I (EBBA-I). Daily salivary levels of 17β-estradiol throughout an entire menstrual cycle were measured at the reproductive Ecology Laboratory, Harvard University, USA. Computer-assisted mammographic density (Madena) was obtained from digitized mammograms taken at day 7-12 of the menstrual cycle. Uniand multivariable regression models were used to study the associations between hormones and premenopausal percent mammographic density. Results: Among women with a mean age of 30,7 years, a mean premenopausal percent mammographic density of 29.8 % was observed. Throughout the menstrual cycle when comparing women with a high percent mammographic density (≥28.5%) to women with a low percent mammographic density (<28.5%), we observed insulin, IGF-1 and IGFBP-3 independently and in combination with cycling 17β-estradiol to predict premenopausal percent mammographic density. We observed among women with either serum insulin ≥ 89 pmol/, IGF-1 ≥ 24 nmol/l, IGFBP-3 ≥ 100 nmol/l, having a high ( 28.5%) versus a low (<28.5%) percent mammographic density was associated with an increase in overall average 17β-estradiol of 4.0 %, 10.9 % and 14.9%, respectively. Moreover, we observed a higher adjusted Odds Ratio (OR) for having a high percent mammographic density for each standard deviation (SD) increase in overall average 17β-estradiol, insulin, IGF-1 and IGFBP-3: 17β-estradiol, 1.55 (1.06-2.27); insulin, 1.62 (0.76-3.48), IGF-1, 1.90 (1.10-3.27); IGFBP-3, 1.88 (1.05-3.37) (adjusted for age, body mass index-BMI kg/m2)). Conclusion: Our study supports that insulin, IGF-1 and IGFBP-3 independently, and in combination with cycling estrogen, predicts premenopausal mammographic density. These hormones may be important biomarkers in breast cancer control and clinical practice. [ABSTRACT FROM AUTHOR]