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Serum Insulin-Like Growth Factors, Insulin-Like Growth Factor Binding Proteins, and Breast Cancer Risk in Postmenopausal Women

¹ Medical Department V and ² Medical Research Laboratories, Aarhus Kommunehospital, Aarhus, Denmark; ³ Danish Cancer Society, Institute of Cancer Epidemiology, Copenhagen, Denmark; and ⁴ Department of Clinical Epidemiology, Aalborg and Aarhus University Hospital, Denmark

Requests for reprints: Henning Grønbæk, Medical Department V, Aarhus Kommunehospital, Norrebrogade 44, DK-8000 Aarhus C, Denmark. Phone: 45-89492800; Fax: 45-89492820. E-mail: henning.gronbaek{at}dadlnet.dk

Background: Studies have shown a positive association between serum insulin-like growth factor (IGF)-I and breast cancer risk in premenopausal but not postmenopausal women. IGF-II and estrogen receptor (ER) status has never been investigated. We examined the association between IGF-I, IGF-II, IGF binding protein (IGFBP)-2, IGFBP-3, and IGFBP-3 protease activity and breast cancer risk in postmenopausal women, taking ER status of the breast cancer into consideration.

Methods: We conducted this case-cohort study within a Danish follow-up study based on 24,697 postmenopausal women. We identified 411 cases with breast cancer and a matched control group including 397 cohort members. We estimated breast cancer risk using Cox regression analysis with adjustment for known breast cancer risk factors.

Results: We observed no association for IGF-I but a positive association between levels of IGFBP-3 and breast cancer risk. Per 500 units higher levels of IGFBP-3, an incidence rate ratio [IRR; 95% confidence interval (95% CI)] of 1.14 (1.00-1.30) was estimated. For ER-positive breast cancer, the IRR (95% CI) was 1.18 (1.05-1.33). IGFBP-3 protease activity was not associated with breast cancer risk. Per 275 units higher levels of IGF-II, an IRR (95% CI) of 1.35 (1.10-1.66) was observed for ER-positive tumors, whereas IGFBP-2 was not associated with breast cancer risk. Adjustment for potential confounders did not change the risk estimate. There was no association between IGF-I, IGF-II, IGFBP-2, or IGFBP-3 and risk of ER-negative breast cancer.

Conclusion: Serum IGFBP-3 and IGF-II levels were positively associated with ER-positive breast cancer risk. This may suggest an important relationship among IGFs, IGFBPs, the ER system, and breast cancer development in postmenopausal women.

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