Effects of tamoxifen on insulin-like growth factors, IGF binding proteins and IGFBP-3 proteolysis in breast cancer patients.

Background: Recently an association between increased serum insulin-like growth factor I (IGF-I) levels and the development of breast cancer was demonstrated. Tamoxifen used in the postoperative treatment of breast cancer patients may exert significant effects on the IGF-I system. Materials and Methods: To examine the effect of Tamoxifen treatment (20 mg/day) on changes in the IGF-I axis in 11 breast cancer patients before and after 4 months of Tamoxifen treatment and compared to 8 healthy subjects. IGF-I, IGF-II, IGFBP-I, IGFBP-2, IGFBP-3 and IGFBP-6 were examined by specific assays. IGFBPs were examined by Western ligand blotting and IGFBP-3 proteolytic activity by specific protease assay. Results: Serum IGF-I was decreased before (63%) and increased during Tamoxifen treatment (60%). Total IGFBP-3 levels measured by IRMA were unchanged, however, intact IGFBP-3 measured by WLB was decreased (58%) before and increased (67%) during Tamoxifen treatment. IGFBP-3 proteolysis was increased before and reduced during treatment. IGFBP-4 and IGFBP-6 were decreased before and increased during Tamoxifen treatment. Conclusion: Significant changes in the IGF system were demonstrated before and during Tamoxifen treatment and may in part be involved in the effects of Tamoxifen treatment in breast cancer patients.