ArticlePharmacogenetics and genomics2017
Comprehensive assessment of cytochromes P450 and transporter genetics with endoxifen concentration during tamoxifen treatment.
Article in Pharmacogenetics and genomics, 2017. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 11 papers.
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Who cites it
11 citing papers in PubMed, 16 citations in OpenAlex.
- Impact of Complex Genetic and Drug-Drug Interactions on Tamoxifen Metabolism and Efficacy.Journal of personalized medicine · 2025Review
- ESR1 and p53 interactome alteration defines mechanisms of tamoxifen response in luminal breast cancer.iScience · 2024Article
- Pharmacogenetics and pharmacokinetics of tamoxifen in a Zimbabwean breast cancer cohort.British journal of clinical pharmacology · 2023Article
- Pharmacokinetics of Tamoxifen and Its Major Metabolites and the Effect of the African Ancestry Specific CYP2D6*17 Variant on the Formation of the Active Metabolite, Endoxifen.Journal of personalized medicine · 2023Article
- Generating a Precision Endoxifen Prediction Algorithm to Advance Personalized Tamoxifen Treatment in Patients with Breast Cancer.Journal of personalized medicine · 2021Review
- Sources of Interindividual Variability.Methods in molecular biology (Clifton, N.J.) · 2021Article
- Clinical Trial:Frontiers in pharmacology · 2019Article
- Patients carrying CYP2C8*3 have shorter systemic paclitaxel exposure.Pharmacogenomics · 2019Article
- Cytochrome P450 Genetic Variation Associated with Tamoxifen Biotransformation in American Indian and Alaska Native People.Clinical and translational science · 2018Article
- Pharmacogenomics Guided-Personalization of Warfarin and Tamoxifen.Journal of personalized medicine · 2017Review
- Novel Strategies on Personalized Medicine for Breast Cancer Treatment: An Update.International journal of molecular sciences · 2017Review
Corrections and comments
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Authors and funding
13 authors at 6 institutions in 1 country.
Funding
Abstract
objectivesTamoxifen bioactivation to endoxifen is mediated primarily by CYP2D6; however, considerable variability remains unexplained. Our aim was to perform a comprehensive assessment of the effect of genetic variation in tamoxifen-relevant enzymes and transporters on steady-state endoxifen concentrations. PATIENTS AND
methodsComprehensive genotyping of CYP enzymes and transporters was performed using the iPLEX ADME PGx Pro Panel in 302 tamoxifen-treated breast cancer patients. Predicted activity phenotype for 19 enzymes and transporters were analyzed for univariate association with endoxifen concentration, and then adjusted for CYP2D6 and clinical covariates.
resultsIn univariate analysis, higher activity of CYP2C8 (regression β=0.22, P=0.020) and CYP2C9 (β=0.20, P=0.04), lower body weight (β=-0.014, P<0.0001), and endoxifen measurement during winter (each β<-0.39, P=0.002) were associated with higher endoxifen concentrations. After adjustment for the CYP2D6 diplotype, weight, and season, CYP2C9 remained significantly associated with higher concentrations (P=0.02), but only increased the overall model R by 1.3%.
conclusionOur results further support a minor contribution of CYP2C9 genetic variability toward steady-state endoxifen concentrations. Integration of clinician and genetic variables into individualized tamoxifen dosing algorithms would marginally improve their accuracy and potentially enhance tamoxifen treatment outcomes.
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