ArticleBritish journal of pharmacology2014
Simulation with cells in vitro of tamoxifen treatment in premenopausal breast cancer patients with different CYP2D6 genotypes.
Article in British journal of pharmacology, 2014. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 22 papers, 1 of them a synthesis that pooled it.
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Who cites it
22 citing papers in PubMed, 1 synthesis or guideline pooled it, 38 citations in OpenAlex.
- Clinical Pharmacogenetics Implementation Consortium (CPIC) Guideline for CYP2D6 and Tamoxifen Therapy.Clinical pharmacology and therapeutics · 2018Guideline
- Estrogen Receptors as Key Factors in Carcinogenesis.Biomedicines · 2025Review
- Article
- Endoxifen downregulates AKT phosphorylation through protein kinase C beta 1 inhibition in ERα+ breast cancer.NPJ breast cancer · 2023Article
- Article
- Chinese breast cancer patients with CYP2D6*10 mutant genotypes have a better prognosis with toremifene than with tamoxifen.Asia-Pacific journal of clinical oncology · 2022Article
- Endoxifen, an Estrogen Receptor Targeted Therapy: From Bench to Bedside.Endocrinology · 2021Review
- Manipulating Estrogenic/Anti-Estrogenic Activity of Triphenylethylenes towards Development of Novel Anti-Neoplastic SERMs.International journal of molecular sciences · 2021Article
- Development and Characterization of Novel Endoxifen-Resistant Breast Cancer Cell Lines Highlight Numerous Differences from Tamoxifen-Resistant Models.Molecular cancer research : MCR · 2021Article
- Complex interactions of lovastatin with 10 chemotherapeutic drugs: a rigorous evaluation of synergism and antagonism.BMC cancer · 2021Article
- The Influences of Adherence to Tamoxifen and CYP2D6 Pharmacogenetics on Plasma Concentrations of the Active Metabolite (Z)-Endoxifen in Breast Cancer.Clinical and translational science · 2020Observational
- Hormonal status affects plasma exposure of tamoxifen and its main metabolites in tamoxifen-treated breast cancer patients.BMC pharmacology & toxicology · 2019Article
- The development of endoxifen for breast cancer.Clinical advances in hematology & oncology : H&O · 2018Article
- First-in-Human Phase I Study of the Tamoxifen Metabolite Z-Endoxifen in Women With Endocrine-Refractory Metastatic Breast Cancer.Journal of clinical oncology : official journal of the American Society of Clinical Oncology · 2017Article
- An Antiestrogenic Activity Score for tamoxifen and its metabolites is associated with breast cancer outcome.Breast cancer research and treatment · 2017Article
- 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
- Article
- Proven value of translational research with appropriate animal models to advance breast cancer treatment and save lives: the tamoxifen tale.British journal of clinical pharmacology · 2015Article
- Tamoxifen metabolism predicts drug concentrations and outcome in premenopausal patients with early breast cancer.The pharmacogenomics journal · 2015Observational
- The new biology of estrogen-induced apoptosis applied to treat and prevent breast cancer.Endocrine-related cancer · 2015Review
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Authors and funding
8 authors at 4 institutions in 2 countries.
Funding
Abstract
background and purposeTamoxifen is a prodrug that is metabolically activated by 4-hydroxylation to the potent primary metabolite 4-hydroxytamoxifen (4OHT) or via another primary metabolite N-desmethyltamoxifen (NDMTAM) to a biologically active secondary metabolite endoxifen through a cytochrome P450 2D6 variant system (CYP2D6). To elucidate the mechanism of action of tamoxifen and the importance of endoxifen for its effect, we determined the anti-oestrogenic efficacy of tamoxifen and its metabolites, including endoxifen, at concentrations corresponding to serum levels measured in breast cancer patients with various CYP2D6 genotypes (simulating tamoxifen treatment). EXPERIMENTAL APPROACH: The biological effects of tamoxifen and its metabolites on cell growth and oestrogen-responsive gene modulation were evaluated in a panel of oestrogen receptor-positive breast cancer cell lines. Actual clinical levels of tamoxifen metabolites in breast cancer patients were used in vitro along with actual levels of oestrogens observed in premenopausal patients taking tamoxifen. KEY
resultsTamoxifen and its primary metabolites (4OHT and NDMTAM) only partially inhibited the stimulant effects of oestrogen on cells. The addition of endoxifen at concentrations corresponding to different CYP2D6 genotypes was found to enhance the anti-oestrogenic effect of tamoxifen and its metabolites with an efficacy that correlated with the concentration of endoxifen; at concentrations corresponding to the extensive metabolizer genotype it further inhibited the actions of oestrogen. In contrast, lower concentrations of endoxifen (intermediate and poor metabolizers) had little or no anti-oestrogenic effects. CONCLUSIONS AND IMPLICATIONS: Endoxifen may be a clinically relevant metabolite in premenopausal patients as it provides additional anti-oestrogenic actions during tamoxifen treatment.
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