Tamoxifen Metabolite Concentrations, CYP2D6 Genotype, and Breast Cancer Outcomes

• DOI: 10.1038/clpt.2011.32
• Publication Date: 2011-03-23T15:55:46Z
• Authors: L Madlensky; L Natarajan; S Tchu; M Pu; J Mortimer; S W Flatt; D M Nikoloff; G Hillman; M R Fontecha; H J Lawrence; B A Parker; A H B Wu; J P Pierce
• Keywords: Genotype; Breast Neoplasms; Middle Aged; 3. Good health; Cohort Studies; Tamoxifen; 03 medical and health sciences; Phenotype; Treatment Outcome; 0302 clinical medicine; Cytochrome P-450 CYP2D6; Humans; Female

We explored whether breast cancer outcomes are associated with endoxifen and other metabolites of tamoxifen examined potential correlates concentration levels in serum including cytochrome P450 2D6 (CYP2D6) metabolizer phenotype body mass index (BMI). Concentration tamoxifen, endoxifen, 4-hydroxytamoxifen (4OH-tamoxifen), N-desmethyltamoxifen (ND-tamoxifen) were measured from samples taken 1,370 patients estrogen receptor (ER)-positive who participating the Women's Healthy Eating Living (WHEL) Study. tested these for possible associations found that not 4-hydroxytamoxifen, ND-tamoxifen. For a threshold was identified, women upper four quintiles appearing to have 26% lower recurrence rate than bottom quintile (hazard ratio (HR) = 0.74; 95% confidence interval (CI), (0.55–1.00)). The predictors this higher-risk poor/intermediate genotype, higher BMI, concentrations as compared mean cohort whole. This study suggests there is minimal above which effective against ~80% takers attain threshold. Clinical Pharmacology & Therapeutics (2011) 89 5, 718–725. doi:10.1038/clpt.2011.32