ArticleBritish journal of clinical pharmacology2016
Association of CYP2C19*2 and associated haplotypes with lower norendoxifen concentrations in tamoxifen-treated Asian breast cancer patients.
Article in British journal of clinical pharmacology, 2016. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 14 papers, 3 of them syntheses that pooled it.
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Who cites it
14 citing papers in PubMed, 3 syntheses or guidelines pooled it, 24 citations in OpenAlex.
- Pooled it
- Association between genetic polymorphisms in cytochrome P450 enzymes and survivals in women with breast cancer receiving adjuvant endocrine therapy: a systematic review and meta-analysis.Expert reviews in molecular medicine · 2022Pooled it
- Clinical Pharmacogenetics Implementation Consortium (CPIC) Guideline for CYP2D6 and Tamoxifen Therapy.Clinical pharmacology and therapeutics · 2018Guideline
- Genomic landscape of drug binding and pharmacogenetic variation across diverse populations using SNPdrug3D.Nature communications · 2026Article
- Genetic variants ofJournal of Taibah University Medical Sciences · 2026Article
- A multi-ancestry genome-wide study of tamoxifen metabolism and breast cancer recurrence.NPJ breast cancer · 2026Article
- From Genotype to Therapeutic Monitoring: Enhancing Tamoxifen Efficacy in Breast Cancer Treatment.Journal of clinical pharmacology · 2025Article
- Impact of Complex Genetic and Drug-Drug Interactions on Tamoxifen Metabolism and Efficacy.Journal of personalized medicine · 2025Review
- A Hypothesized Therapeutic Role of (Z)-Endoxifen in Duchenne Muscular Dystrophy (DMD).Degenerative neurological and neuromuscular disease · 2025Article
- ClinicalCancers · 2021Review
- Effect of CYP2C19 genotypes on tamoxifen metabolism and early-breast cancer relapse.Scientific reports · 2021Article
- Comprehensive assessment of cytochromes P450 and transporter genetics with endoxifen concentration during tamoxifen treatment.Pharmacogenetics and genomics · 2017Article
- CYP2C19*2 and CYP2C19*17 variants and effect of tamoxifen on breast cancer recurrence: Analysis of the International Tamoxifen Pharmacogenomics Consortium dataset.Scientific reports · 2017Article
- Association of CYP2C19*2 and associated haplotypes with lower norendoxifen concentrations in tamoxifen-treated Asian breast cancer patients.British journal of clinical pharmacology · 2016Article
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Authors and funding
13 authors at 5 institutions in 3 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
aimThe aim was to examine the influence of CYP2C19 variants and associated haplotypes on the disposition of tamoxifen and its metabolites, particularly norendoxifen (NorEND), in Asian patients with breast cancer.
methodsSixty-six CYP2C19 polymorphisms were identified in healthy Asians (n = 240), of which 14 were found to be tightly linked with CYP2C19*2, CYP2C19*3 and CYP2C19*17. These 17 SNPs were further genotyped in Asian breast cancer patients receiving tamoxifen (n = 201). Steady-state concentrations of tamoxifen and its metabolites were quantified using liquid chromatography–mass spectrometry. Non-parametric tests and regression methods were implemented to evaluate genotypic–phenotypic associations and haplotypic effects of the SNPs.
resultsCYP2C19 functional polymorphisms and their linked SNPs were not significantly associated with plasma concentrations of tamoxifen and its main metabolites N-desmethyltamoxifen, (Z)-4-hydroxytamoxifen and (Z)-Endoxifen. However, CYP2C19*2 and its seven linked SNPs were significantly associated with lower NorEND concentrations, MRNorEND/NDDM and MRNorEND/(Z)-END. Specifically, patients carrying the CYP2C19*2 variant allele A had significantly lower NorEND concentrations [median (range), GG vs. GA vs. AA: 1.51 (0.38–3.28) vs. 1.28 (0.30–3.36) vs. 1.15 ng ml−1 (0.26–2.45, P = 0.010)] as well as significantly lower MRNorEND/(Z)-END [GG vs. GA vs. AA: 9.40 (3.27–28.35) vs. 8.15 (2.67–18.9) vs. 6.06 (4.47–14.6), P < 0.0001] and MRNorEND/NDDM [GG vs. GA vs. AA: 2.75 (0.62–6.26) vs. 2.43 (0.96–4.18) vs. 1.75 (1.10–2.49), P < 0.00001]. CYP2C19 H2 haplotype, which included CYP2C19*2, was also significantly associated with lower NorEND concentrations (P = 0.0020), MRNorEND/NDDM (P < 0.0001) and MRNorEND/(Z)-END (P < 0.0001), indicating significantly lower formation rates of NorEND.
conclusionThese data highlight the potential relevance of CYP2C19 pharmacogenetics in influencing NorEND concentrations in tamoxifen-treated patients, which may influence treatment outcomes.
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