ArticleBreast cancer research and treatment2012
Dose-adjustment study of tamoxifen based on CYP2D6 genotypes in Japanese breast cancer patients.
Article in Breast cancer research and treatment, 2012. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 39 papers, 1 of them a synthesis that pooled it.
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Who cites it
39 citing papers in PubMed, 1 synthesis or guideline pooled it, 92 citations in OpenAlex.
- Pharmacogenetics of Toxicities Related to Endocrine Treatment in Breast Cancer: A Systematic Review and Meta-analysis.Cancer genomics & proteomicsPooled it
- Therapeutic Drug Monitoring of Endoxifen for Tamoxifen Precision Dosing: Feasible in Patients with Hormone-Sensitive Breast Cancer.Clinical pharmacokinetics · 2022Trial
- Trial
- Article
- Influence of CYP2D6 polymorphisms on tamoxifen side effects in patients with breast cancer.Clinical & translational oncology : official publication of the Federation of Spanish Oncology Societies and of the National Cancer Institute of Mexico · 2025Article
- CYP2D6 polymorphisms and endoxifen concentration in Chinese patients with breast cancer.BMC cancer · 2025Article
- 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
- Review
- Impact of Irradiation on the Pharmacokinetics and Biotransformation of Tamoxifen.Frontiers in oncology · 2022Article
- Pharmacogenetics of tamoxifen therapy in Asian populations: from genetic polymorphism to clinical outcomes.European journal of clinical pharmacology · 2021Review
- Generating a Precision Endoxifen Prediction Algorithm to Advance Personalized Tamoxifen Treatment in Patients with Breast Cancer.Journal of personalized medicine · 2021Review
- Impairment of endoxifen formation in tamoxifen-treated premenopausal breast cancer patients carrying reduced-function CYP2D6 alleles.British journal of clinical pharmacology · 2021Article
- Simulation-Based Assessment of the Impact of Non-Adherence on Endoxifen Target Attainment in Different Tamoxifen Dosing Strategies.Pharmaceuticals (Basel, Switzerland) · 2021Article
- Evaluating the Risk of Breast Cancer Recurrence and Metastasis After Adjuvant Tamoxifen Therapy by Integrating Polymorphisms in Cytochrome P450 Genes and Clinicopathological Characteristics.Frontiers in oncology · 2021Article
- Pharmacogenomic-pharmacokinetic study of selective estrogen-receptor modulators with intra-patient dose escalation in breast cancer.Breast cancer (Tokyo, Japan) · 2019Article
- Clinical Trial:Frontiers in pharmacology · 2019Article
- Application of PBPK Modeling and Virtual Clinical Study Approaches to Predict the Outcomes of CYP2D6 Genotype-Guided Dosing of Tamoxifen.CPT: pharmacometrics & systems pharmacology · 2018Article
- Cytochrome P450 Genetic Variation Associated with Tamoxifen Biotransformation in American Indian and Alaska Native People.Clinical and translational science · 2018Article
- Precision medicine: does ethnicity information complement genotype-based prescribing decisions?Therapeutic advances in drug safety · 2018Review
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9 authors at 4 institutions in 1 country.
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No grant is acknowledged in the PubMed record.
Abstract
CYP2D6 is a key enzyme responsible for the metabolism of tamoxifen to active metabolites, endoxifen, and 4-hydroxytamoxifen. The breast cancer patients who are heterozygous and homozygous for decreased-function and null alleles of CYP2D6 showed lower plasma concentrations of endoxifen and 4-hydroxytamoxifen compared to patients with homozygous-wild-type allele, resulting in worse clinical outcome in tamoxifen therapy. We recruited 98 Japanese breast cancer patients, who had been taking 20 mg of tamoxifen daily as adjuvant setting. For the patients who have one or no normal allele of CYP2D6, dosages of tamoxifen were increased to 30 and 40 mg/day, respectively. The plasma concentrations of tamoxifen and its metabolites were measured at 8 weeks after dose-adjustment using liquid chromatography-tandem mass spectrometry. Association between tamoxifen dose and the incidence of adverse events during the tamoxifen treatment was investigated. In the patients with CYP2D6*1/*10 and CYP2D6*10/*10, the mean plasma endoxifen levels after dose increase were 1.4- and 1.7-fold higher, respectively, than those before the increase (P < 0.001). These plasma concentrations of endoxifen achieved similar level of those in the CYP2D6*1/*1 patients receiving 20 mg/day of tamoxifen. Plasma 4-hydroxytamoxifen concentrations in the patients with CYP2D6*1/*10 and CYP2D6*10/*10 were also significantly increased to the similar levels of the CYP2D6*1/*1 patients according to the increasing tamoxifen dosages (P < 0.001). The incidence of adverse events was not significantly different between before and after dose adjustment. This study provides the evidence that dose adjustment is useful for the patients carrying CYP2D6*10 allele to maintain the effective endoxifen level.
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