Serum insulin-like growth factors, insulin-like growth factor binding proteins, and breast cancer risk in postmenopausal women.

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.