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

Research output: Contribution to journalArticle

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 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.

Original languageEnglish
Pages (from-to)21-27
Number of pages7
JournalBreast Cancer Research and Treatment
Volume69
Issue number1
DOIs
Publication statusPublished - 2001

Keywords

  • Biomarkers
  • Breast neoplasms
  • Chemoprevention
  • Growth factors
  • Somatomedins
  • Tamoxifen

ASJC Scopus subject areas

  • Oncology
  • Cancer Research

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