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Effect of low dose tamoxifen on the insulin-like growth factor system in healthy women

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Abstract

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 20mg/day (n=26), 10mg/day (n=23) or 10mg/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 10ng/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.

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Bonanni, B., Johansson, H., Gandini, S. et al. Effect of low dose tamoxifen on the insulin-like growth factor system in healthy women. Breast Cancer Res Treat 69, 21–27 (2001). https://doi.org/10.1023/A:1012241505717

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