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Circulating Insulin-Like Growth Factor-I and Binding Protein-3 and the Risk of Breast Cancer

¹ Cancer Epidemiology Centre, The Cancer Council Victoria, Melbourne, Victoria, Australia; ² Centre for Molecular, Environmental, Genetic, and Analytical Epidemiology, University of Melbourne, Melbourne, Victoria, Australia; ³ Hanson Institute, Institute of Medical and Veterinary Science, Adelaide, South Australia, Australia; and ⁴ Dame Roma Mitchell Cancer Research Laboratories, School of Medicine, University of Adelaide, Adelaide, South Australia, Australia

Requests for reprints: Graham Giles, Cancer Epidemiology Centre, The Cancer Council Victoria, 1 Rathdowne Street, Carlton, Melbourne, Victoria 3053, Australia. Phone: 61-39635-5155; Fax: 61-39635-5330. E-mail: graham.giles{at}cancervic.org.au

Four meta-analyses and literature reviews have concluded that a positive association exists between circulating levels of insulin-like growth factor-I (IGF-I) and IGF-binding protein-3 (IGFBP-3) and breast cancer risk for premenopausal but not postmenopausal women. Recently, a large prospective study reported an association with IGF-I and IGFBP-3 concentration for breast cancer diagnosed after, but not before, the age of 50 years; and in a large cohort of primarily premenopausal women, IGF-I and IGFBP-3 were not associated with breast cancer risk. We did a case-cohort study within the Melbourne Collaborative Cohort Study, which included a random sample of 1,901 women (subcohort) and 423 breast cancer cases diagnosed during a mean of 9.1 years of follow-up. IGF-I and IGFBP-3 concentrations were measured in plasma collected at baseline. The association between quartiles of IGF concentration and breast cancer risk was tested using a Cox model adjusted for known and potential confounders. The hazard ratio (HR) for breast cancer comparing the fourth with the first quartiles was 1.20 [95% confidence interval (95% CI), 0.87-1.65] for IGF-I and 1.09 (95% CI, 0.78-1.53) for IGFBP-3. Both associations varied with age: for IGF-I, the HRs for breast cancer comparing the fourth with the first quartiles were 0.60 (95% CI, 0.25-1.45) before age 50 and 1.61 (95% CI, 1.04-2.51) after age 60 (test for the log-linear trend of HR according to age, P = 0.05); for IGFBP-3, the HRs were 0.79 (95% CI, 0.34-1.83) before age 50 and 1.62 (95% CI, 1.03-2.55) after age 60 (test for log-linear trend, P = 0.08). IGF-I and IGFBP-3 were positively associated with breast cancer risk in older women but not in younger women. More prospective studies are needed to clarify the age dependence of the association between IGF-I and IGFBP-3 and breast cancer. (Cancer Epidemiol Biomarkers Prev 2007;16(4):763–8)

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