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

Breast Cancer Res Treat. 2001 Sep;69(1):21-7. doi: 10.1023/a:1012241505717.


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
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Anticarcinogenic Agents / administration & dosage
  • Anticarcinogenic Agents / pharmacology*
  • Biomarkers, Tumor / analysis*
  • Breast Neoplasms / prevention & control*
  • Dose-Response Relationship, Drug
  • Female
  • Humans
  • Insulin-Like Growth Factor I / analysis*
  • Insulin-Like Growth Factor I / biosynthesis
  • Middle Aged
  • Placebos
  • Tamoxifen / administration & dosage
  • Tamoxifen / pharmacology*


  • Anticarcinogenic Agents
  • Biomarkers, Tumor
  • Placebos
  • Tamoxifen
  • Insulin-Like Growth Factor I