Fasting insulin and endogenous hormones in relation to premenopausal breast density (Canada)
- 242 Downloads
Mammographic breast density (BD) is associated with increased risk of breast cancer. This study asks which circulating metabolic and reproductive biomarkers are associated with BD, particularly dense breast area, in premenopausal women not taking exogenous hormones.
In a cross-sectional study, 299 premenopausal women aged 40–49 completed questionnaires, provided a fasting blood sample, had height, weight, percentage body fat, waist and hip measurements taken, and attended a screening mammogram. Multivariate linear regression was used to calculate adjusted means for percentage BD, absolute dense and non-dense area, across categories of covariates, adjusted for day of menstrual cycle, age, parity, body mass index, percentage body fat, and ethnicity.
Fasting insulin levels were inversely associated, and insulin-like growth factor-binding protein 1 levels directly associated with percentage BD, but lost statistical significance after multivariate adjustment. Sex hormone-binding globulin levels were directly associated with percentage BD, still significant after multivariate adjustment (p = 0.03). A significant inverse dose–response association was observed between progesterone levels and dense area (p < 0.01).
Breast density in premenopausal women seems unrelated or inversely related to insulin resistance, levels of insulin-like growth factor 1 and its binding proteins, and levels of sex steroids; therefore, the mechanism by which radiodensity on a mammogram is related to breast cancer risk remains unclear.
KeywordsMammographic breast density Insulin resistance Premenopausal Insulin-like growth factors Sex steroid hormones Breast cancer
The research was sponsored by the Canadian Institutes of Health Research and the Canadian Breast Cancer Research Alliance. We thank Teresa Switzer, Treena McDonald, Rozmin Janoo-Gilani, Donna Kan, and June Song for help with operational aspects.
Conflicts of interest
The authors declare that they have no conflict of interest.
- 1.World Cancer Research Fund Panel/American Institute for Cancer Research (2007) Food, nutrition, physical activity and the prevention of cancer: a global perspective. WCRF/American Institute of Cancer Research, WashingtonGoogle Scholar
- 7.Walker K, Fletcher O, Johnson N, Coupland B, McCormack VA, Folkerd E, Gibson L, Hillier SG, Holly JM, Moss S, Dowsett M, Peto J, dos Santos Silva I (2009) Premenopausal mammographic density in relation to cyclic variations in endogenous sex hormone levels, prolactin, and insulin-like growth factors. Cancer Res 69(16):6490–6499. doi: 10.1158/0008-5472.CAN-09-0280 PubMedCrossRefGoogle Scholar
- 15.Woolcott CG, Courneya KS, Boyd NF, Yaffe MJ, McTiernan A, Brant R, Jones CA, Stanczyk FZ, Terry T, Cook LS, Wang Q, Friedenreich CM (2013) Association between sex hormones, glucose homeostasis, adipokines, and inflammatory markers and mammographic density among postmenopausal women. Breast Cancer Res Treat 139(1):255–265. doi: 10.1007/s10549-013-2534-x PubMedCrossRefGoogle Scholar
- 19.Boyd NF, Byng JW, Jong RA, Fishell EK, Little LE, Miller AB, Lockwood GA, Tritchler DL, Yaffe MJ (1995) Quantitative classification of mammographic densities and breast cancer risk: results from the Canadian National Breast Screening Study. J Natl Cancer Inst 87(9):670–675PubMedCrossRefGoogle Scholar
- 24.Rice MS, Tworoger SS, Rosner BA, Pollak MN, Hankinson SE, Tamimi RM (2012) Insulin-like growth factor-1, insulin-like growth factor-binding protein-3, growth hormone, and mammographic density in the Nurses’ Health Studies. Breast Cancer Res Treat 136(3):805–812. doi: 10.1007/s10549-012-2303-2 PubMedCentralPubMedCrossRefGoogle Scholar
- 26.Jayagopal V, Kilpatrick ES, Jennings PE, Hepburn DA, Atkin SL (2003) The biological variation of testosterone and sex hormone-binding globulin (SHBG) in polycystic ovarian syndrome: implications for SHBG as a surrogate marker of insulin resistance. J Clin Endocrinol Metab 88(4):1528–1533PubMedCrossRefGoogle Scholar
- 28.Yong M, Atkinson C, Newton KM, Aiello Bowles EJ, Stanczyk FZ, Westerlind KC, Holt VL, Schwartz SM, Leisenring WM, Lampe JW (2009) Associations between endogenous sex hormone levels and mammographic and bone densities in premenopausal women. Cancer Causes Control 20(7):1039–1053. doi: 10.1007/s10552-009-9321-3 PubMedCentralPubMedCrossRefGoogle Scholar
- 39.SMPBC (2004) 2003/2004 Annual report. Screening Mammography Program of BC, VancouverGoogle Scholar