ArticleBMC cancer2015
Limited predictive value of achieving beneficial plasma (Z)-endoxifen threshold level by CYP2D6 genotyping in tamoxifen-treated Polish women with breast cancer.
Article in BMC cancer, 2015. The graph could read no effect estimate from its abstract, so it casts no vote on the map. It is linked to trial NCT03504631 (Genotyping and Phenotyping of CYP2D6 as Predictor of Z-endoxifen Plasma Levels in Breast Cancer Patients on Tamoxifen Treatment), which is not on this map. Cited by 10 papers.
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Genotyping and Phenotyping of CYP2D6 as Predictor of Z-endoxifen Plasma Levels in Breast Cancer Patients on Tamoxifen Treatment
Who cites it
10 citing papers in PubMed, 21 citations in OpenAlex.
- Resolving CYP2D6 Structural Complexity with Long-Read Sequencing: Implications for Tamoxifen Precision Dosing in Thai Breast Cancer Patients.Clinical pharmacology and therapeutics · 2026Article
- Development and validation of a liquid chromatography-mass spectrometry assay for quantification of Z- and E- isomers of endoxifen and its metabolites in plasma from women with estrogen receptor positive breast cancer.Journal of chromatography. B, Analytical technologies in the biomedical and life sciences · 2023Article
- Article
- Generating a Precision Endoxifen Prediction Algorithm to Advance Personalized Tamoxifen Treatment in Patients with Breast Cancer.Journal of personalized medicine · 2021Review
- Volumetric Absorptive Microsampling as a New Biosampling Tool for Monitoring of Tamoxifen, Endoxifen, 4-OH Tamoxifen and N-Desmethyltamoxifen in Breast Cancer Patients.Drug design, development and therapy · 2021Article
- Predicting steady-state endoxifen plasma concentrations in breast cancer patients by CYP2D6 genotyping or phenotyping. Which approach is more reliable?Pharmacology research & perspectives · 2020Article
- Non-Journal of clinical medicine · 2019Article
- Dynamic Effects of CYP2D6 Genetic Variants in a Set of Poor Metaboliser Patients with Infiltrating Ductal Cancer Under Treatment with Tamoxifen.Scientific reports · 2019Article
- CYP2D6-inhibiting medication use and inherited CYP2D6 variation in relation to adverse breast cancer outcomes after tamoxifen therapy.Cancer causes & control : CCC · 2019Article
- Association of CYP2D6*10 (c.100C>T) polymorphisms with clinical outcome of breast cancer after tamoxifen adjuvant endocrine therapy in Chinese population.American journal of translational research · 2016Article
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Authors and funding
11 authors at 3 institutions in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
backgroundTamoxifen, the most frequently used drug for treating estrogen receptor-positive breast cancer, must be converted into active metabolites to exert its therapeutic efficacy, mainly through CYP2D6 enzymes. The objective of this study was to investigate the impact of CYP2D6 polymorphisms on (Z)-endoxifen-directed tamoxifen metabolism and to assess the usefulness of CYP2D6 genotyping for identifying patients who are likely to have insufficient (Z)-endoxifen concentrations to benefit from standard therapy.
methodsBlood samples from 279 Polish women with breast cancer receiving tamoxifen 20 mg daily were analyzed for CYP2D6 genotype and drug metabolite concentration. Steady-state plasma levels of tamoxifen and its 14 metabolites were measured by using the ultra-performance liquid chromatography tandem mass spectrometry (UPLC-MS/MS) method.
resultsIn nearly 60 % of patients, including over 30 % of patients with fully functional CYP2D6, (Z)-endoxifen concentration was below the predefined threshold of therapeutic efficacy. The most frequently observed CYP2D6 genotype was EM/PM (34.8 %), among which 83.5 % of patients had a combination of wild-type and *4 alleles. Plasma concentration of five metabolites was significantly correlated with CYP2D6 genotype. For the first time, we identified an association between decreased (E/Z)-4-OH-N-desmethyl-tamoxifen-β-D-glucuronide levels (r (2) = 0.23; p < 10(-16)) and increased CYP2D6 functional impairment. The strongest correlation was observed for (Z)-endoxifen, whose concentration was significantly lower in groups of patients carrying at least one CYP2D6 null allele, compared with EM/EM patients. The CYP2D6 genotype accounted for plasma level variability of (Z)-endoxifen by 27 % (p < 10(-16)) and for the variability of metabolic ratio indicating (Z)-endoxifen-directed metabolism of tamoxifen by 51 % (p < 10(-43)).
conclusionsThe majority of breast cancer patients in Poland may not achieve a therapeutic level of (Z)-endoxifen upon receiving a standard dose of tamoxifen. This finding emphasizes the limited value of CYP2D6 genotyping in routine clinical practice for identifying patients who might not benefit from the therapy. In its place, direct monitoring of plasma steady-state (Z)-endoxifen concentration should be performed to personalize and optimize the treatment.
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