ArticleJournal of the National Cancer Institute2014
Pharmacological relevance of endoxifen in a laboratory simulation of breast cancer in postmenopausal patients.
Article in Journal of the National Cancer Institute, 2014. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 13 papers, 1 of them a synthesis that pooled it.
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Who cites it
13 citing papers in PubMed, 1 synthesis or guideline pooled it, 17 citations in OpenAlex.
- Clinical Pharmacogenetics Implementation Consortium (CPIC) Guideline for CYP2D6 and Tamoxifen Therapy.Clinical pharmacology and therapeutics · 2018Guideline
- Progress in Heterocyclic Hybrids for Breast Cancer Therapy: Emerging Trends, Hybridization Techniques, Mechanistic Pathways and SAR Insights.Mini reviews in medicinal chemistry · 2026Review
- Endoxifen downregulates AKT phosphorylation through protein kinase C beta 1 inhibition in ERα+ breast cancer.NPJ breast cancer · 2023Article
- Endoxifen, an Estrogen Receptor Targeted Therapy: From Bench to Bedside.Endocrinology · 2021Review
- Article
- Chaperone mediated detection of small molecule target binding in cells.Nature communications · 2020Article
- Role for the transcriptional activator ZRF1 in early metastatic events in breast cancer progression and endocrine resistance.Oncotarget · 2018Article
- 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
- Tamoxifen Resistance: Emerging Molecular Targets.International journal of molecular sciences · 2016Review
- The effects of endoxifen and other major metabolites of tamoxifen on the sulfation of estradiol catalyzed by human cytosolic sulfotransferases hSULT1E1 and hSULT1A1*1.Drug metabolism and disposition: the biological fate of chemicals · 2015Article
- The new biology of estrogen-induced apoptosis applied to treat and prevent breast cancer.Endocrine-related cancer · 2015Review
Corrections and comments
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Authors and funding
7 authors at 1 institution in 1 country.
Funding
Abstract
backgroundTamoxifen is metabolically activated via a CYP2D6 enzyme system to the more potent hydroxylated derivatives 4-hydroxytamoxifen and endoxifen. This study addresses the pharmacological importance of endoxifen by simulating clinical scenarios in vitro.
methodsClinical levels of tamoxifen metabolites in postmenopausal breast cancer patients previously genotyped for CYP2D6 were used in vitro along with clinical estrogen levels (estrone and estradiol) in postmenopausal patients determined in previous studies. The biological effects on cell growth were evaluated in a panel of estrogen receptor-positive breast cancer cell lines via cell proliferation assays and real-time polymerase chain reaction (PCR). Data were analyzed with one- and two-way analysis of variance and Student's t test. All statistical tests were two-sided.
resultsPostmenopausal levels of estrogen-induced proliferation of all test breast cancer cell lines (mean fold induction ± SD vs vehicle control: MCF-7 = 11 ± 1.74, P < .001; T47D = 7.52 ± 0.72, P < .001; BT474 = 1.75 ± 0.23, P < .001; ZR-75-1 = 5.5 ± 1.95, P = .001. Tamoxifen and primary metabolites completely inhibited cell growth regardless of the CYP2D6 genotype in all cell lines (mean fold induction ± SD vs vehicle control: MCF-7 = 1.57 ± 0.38, P = .54; T47D = 1.17 ± 0.23, P = .79; BT474 = 0.96 ± 0.2, P = .98; ZR-75-1 = 0.86 ± 0.67, P = .99). Interestingly, tamoxifen and its primary metabolites were not able to fully inhibit the estrogen-stimulated expression of estrogen-responsive genes in MCF-7 cells (P < .05 for all genes), but the addition of endoxifen was able to produce additional antiestrogenic effect on these genes.
conclusionsThe results indicate that tamoxifen and other metabolites, excluding endoxifen, completely inhibit estrogen-stimulated growth in all cell lines, but additional antiestrogenic action from endoxifen is necessary for complete blockade of estrogen-stimulated genes. Endoxifen is of supportive importance for the therapeutic effect of tamoxifen in a postmenopausal setting.
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