Effect of Blood Tamoxifen Concentrations on Surrogate Biomarkers in a Trial of Dose Reduction in Healthy Women

• DOI: 10.1200/jco.1999.17.9.2633
• Publication Date: 2017-02-24T06:05:40Z
• Authors: Andrea Decensi; Sara Gandini; Aliana Guerrieri-...; Harriet Johansson; Lapo Manetti; Bernardo Bonanni; Maria Teresa Sandri; Antonella Barreca; Alberto Costa; Chris Robertson; Ernst A. Lien
• Keywords: Antiestrogen

PURPOSE: Tamoxifen administered at 20 mg/d has been shown to decrease breast cancer incidence in at-risk women by 50%, but toxicity may limit its broad use, particularly postmenopausal women. Because be dose-dependent, we studied the biologic activity of low concentrations tamoxifen determine plausibility a dose reduction. PATIENTS AND METHODS: We measured blood and main metabolites titration study 105 healthy (placebo, 10 mg on alternate days, mg/d, mg/d). Drug levels after 2 months treatment were correlated with changes surrogate biomarkers different diseases, including lipid profile, cell count, fibrinogen, antithrombin III, osteocalcin, insulin-like growth factor I, promising biomarker cancer. RESULTS: The means (± SD) for N-desmethyltamoxifen (metabolite X) (ng/mL) dose-related, being, respectively, 0 placebo, 26.8 ± 15.1 43.7 22.5 every other day, 51.2 24.1 90.7 48.0 136.0 52.7 230.6 75.0 tamoxifen. At variance, comparable magnitude any drug concentration except platelet count triglycerides levels, latter showing trend an increase increasing concentrations. CONCLUSION: An 80% reduction does not seem affect cardiovascular or risk fact have more favorable safety profile. Additional studies are warranted most appropriate this agent.