title: Effect of low dose tamoxifen on the insulin-like growth factor system in healthy women.
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.
authors.affiliation: Division of Chemoprevention, European Institute of Oncology, Milan, Italy.
authors.forename: B
authors.initials: B
authors.lastname: Bonanni
authors.forename: H
authors.initials: H
authors.lastname: Johansson
authors.forename: S
authors.initials: S
authors.lastname: Gandini
authors.forename: A
authors.initials: A
authors.lastname: Guerrieri-Gonzaga
authors.forename: R
authors.initials: R
authors.lastname: Torrisi
authors.forename: M T
authors.initials: MT
authors.lastname: Sandri
authors.forename: M
authors.initials: M
authors.lastname: Cazzaniga
authors.forename: S
authors.initials: S
authors.lastname: Mora
authors.forename: C
authors.initials: C
authors.lastname: Robertson
authors.forename: E A
authors.initials: EA
authors.lastname: Lien
authors.forename: A
authors.initials: A
authors.lastname: Decensi
mesh_terms: D016588:Anticarcinogenic Agents / Q000008:administration & dosage / Q000494:pharmacology*; D014408:Biomarkers, Tumor / Q000032:analysis*; D001943:Breast Neoplasms / Q000517:prevention & control*; D004305:Dose-Response Relationship, Drug; D005260:Female; D006801:Humans; D007334:Insulin-Like Growth Factor I / Q000032:analysis* / Q000096:biosynthesis; D008875:Middle Aged; D010919:Placebos; D013629:Tamoxifen / Q000008:administration & dosage / Q000494:pharmacology*
chemical_list: D016588:Anticarcinogenic Agents; D014408:Biomarkers, Tumor; D010919:Placebos; D013629:Tamoxifen; D007334:Insulin-Like Growth Factor I