Tamoxifen alters levels of serum insulin-like growth factors and binding proteins in postmenopausal breast cancer patients: A prospective paired cohort study

Background: Recent data suggest that tamoxifen may act by altering serum levels of insulin-like growth factors (IGFs) and their binding proteins (BPs). This prospective paired cohort study evaluated the influence of tamoxifen on serum levels of IGFs and BPs in postmenopausal patients with breast cancer. Methods: Blood was collected from 32 postmenopausal patients with breast cancer before and during tamoxifen therapy for at least 6 months. All patients had undergone primary surgery. Serum concentrations of IGF-I, IGF-II, BP-1, and BP-3 were determined by immunoradiometric assays, and Western ligand blots provided a semiquantitative measurement of BP-2, BP-3, and BP-4. Statistical analysis was performed by paired Student's t-test. Results: Mean serum IGF-1 level was significantly lower after tamoxifen treatment (pretreatment: 116.2 ng/mL +/- 13.6 [SEM] vs. posttreatment: 77.5 ng/mL +/- 7.8, P = .003). In contrast, mean IGF-II levels increased from 651.5 +/- 62.2 ng/mL to 812.5 +/- 35.1 ng/mL during treatment (P = .006), Posttreatment levels of BP-1 (92.9 ng/mL +/- 7.5) were significantly higher compared to the pretreatment values (28.1 ng/mL +/- 4.7; P <.001). Serum concentration of BP-3 also was elevated (pretreatment: 2228.1 ng/mL +/- 145.2 vs, posttreatment: 3539.1 ng/mL +/- 172.3; P <.001). Densitometric measurements showed a similar significant increase in BP-3 (P <.001) as well as BP-4 (P = .017) after hormonal therapy. Levels of BP-2 were not influenced by tamoxifen treatment. Conclusions: These significant alterations in serum concentrations of IGFs and BPs with tamoxifen therapy suggest that the IGF system is a potential mechanism by which tamoxifen exerts its growth inhibitory effect on breast carcinomas.