NOLVADEX STUDY
Effect of low dose tamoxifen on the insulin-like growth factor system in healthy women.
Bonanni B, Johansson H, Gandini S, Guerrieri-Gonzaga A, Torrisi R, Sandri MT, Cazzaniga M, Mora S, Robertson C, Lien EA, Decensi A.
Division of Chemoprevention, European Institute of Oncology, Milan, Italy.
The use of tamoxifen as a preventive agent may be limited by the increased risk of endometrial cancer and venous thromboembolic events observed in postmenopausal women. We have recently shown a comparable activity of lower doses of tamoxifen on several surrogate biomarkers of cardiovascular disease and breast cancer, including Insulin-like Growth Factor-I (IGF-I). To provide further insight into the effect of tamoxifen at low doses on the IGF system, we have correlated the drug serum levels attained after 2 months of either placebo (n = 32), tamoxifen 20 mg/day (n = 26), 10 mg/day (n = 23) or 10 mg/every other day (n = 29) with the changes in IGF-I, Insulin-like Growth Factor-II (IGF-II), Insulin-like Growth Factor Binding Protein-1 (IGFBP-1), Insulin-like Growth Factor Binding Protein-3 (IGFBP-3), and IGF-I/IGFBP-3 ratio. Compared with placebo, tamoxifen induced a mean +/- standard error (SE) reduction of IGF-I of 16.9 +/- 7.8%, p < 0.05, a non-significant increase of 22.9 +/- 12.2% in IGF-II, an increase in IGFBP-1 of 49.3 +/- 22.7%, p < 0.05, and a non-significant change of IGFBP-3 (-4.0% +/- 9.2). No significant concentration-response relationship was observed between serum tamoxifen concentrations and the biomarker changes except for the ratio of IGF-I/IGFBP-3, which decreased by 1.53 +/- 0.68% for any increase by 10 ng/ml of serum tamoxifen concentration (p = 0.02). Although low tamoxifen concentrations induce a comparable modulation of the IGF family relative to the conventional dose, the lower decrements in the IGF-I/IGFBP-3 ratio observed at low drug concentrations might be associated with a reduced preventive activity. Further studies on the search of the minimal active dose of tamoxifen are warranted.
Publication Types:
Clinical Trial
Randomized Controlled Trial
PMID: 11759825 [PubMed - indexed for MEDLINE]
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ARIMIDEX STUDY
Short-term effects of anastrozole treatment on insulin-like growth factor system in postmenopausal advanced breast cancer patients.
Ferrari L, Martinetti A, Zilembo N, Pozzi P, Buzzoni R, La Torre I, Gattinoni L, Catena L, Vitali M, Celio L, Seregni E, Bombardieri E, Bajetta E.
Nuclear Medicine, Istituto Nazionale per lo Studio e la Cura dei Tumori of Milan, Via G. Venezian, 1, 20133, Milan, Italy
Insulin-like growth factors (IGFs) play a fundamental role in cancer development by acting in both an endocrinal and paracrinal manner, and hormone breast cancer treatments affect the IGF system by modifying circulating growth factor levels. We evaluated total IGF-1, IGF-2, IGF binding protein (IGFBP)-1 and IGFBP-3 in the blood of 34 postmenopausal advanced breast cancer patients (median age 63 years, range 41-85) treated with anastrozole, a non-steroidal structure aromatase inhibitor (NSS-AI). The plasma samples were obtained at baseline, and after 2, 4, 8 and 12 weeks of treatment. The IGFs were quantitated by means of sensitive radioimmunoassays (RIAs). IGF-1 significantly increased during anastrozole treatment (baseline versus 12 weeks, P=0.031), IGF-2 showed a trend towards an increase, and IGFBP-1 constantly but not significantly decreased; IGFBP-3 did not seem to be affected at all. The anastrozole-induced changes in IGFs and IGFBP-1 appeared to be different in the patients receiving a clinical benefit from those observed in non-responders. We have previously shown that letrozole (a different type of NSS-AI) modifies blood IGF-1 levels, and the results of this study of the biological effects of anastrozole on the components of the IGF system confirm our previous observations.
PMID: 11983488 [PubMed - in process]