ArticleBreast cancer research and treatment2012
Tissue distribution of 4-hydroxy-N-desmethyltamoxifen and tamoxifen-N-oxide.
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 19 papers, 1 of them a synthesis that pooled it.
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Who cites it
19 citing papers in PubMed, 1 synthesis or guideline pooled it, 34 citations in OpenAlex.
- Complications and thromboembolic events associated with tamoxifen therapy in patients with breast cancer undergoing microvascular breast reconstruction: a systematic review and meta-analysis.Breast cancer research and treatment · 2017Pooled it
- Impact of short-term low-dose tamoxifen on molecular breast imaging background parenchymal uptake: a pilot study.Breast cancer research : BCR · 2019Trial
- Comprehensive CYP2D6 genotyping improves phenotype classification and highlights methodological pitfalls in tamoxifen-treated breast cancer.BMC cancer · 2026Article
- Enhancing Solid-Phase Extraction of Tamoxifen and Its Metabolites from Human Plasma Using MOF-Integrated Polyacrylonitrile Composites: A Study on CuBTC and ZIF-8 Efficacy.Nanomaterials (Basel, Switzerland) · 2023Article
- Effect of Tamoxifen on Proteome Expression duringJournal of proteome research · 2023Article
- CRISISS: A Novel, Transcriptionally and Post-Translationally Inducible CRISPR/Cas9-Based Cellular Suicide Switch.International journal of molecular sciences · 2023Article
- Identification of the estrogen receptor beta as a possible new tamoxifen-sensitive target in diffuse large B-cell lymphoma.Blood cancer journal · 2022Article
- Autophagy Triggers Tamoxifen Resistance in Human Breast Cancer Cells by Preventing Drug-Induced Lysosomal Damage.Cancers · 2021Article
- Integrated Data Analysis of Six Clinical Studies Points Toward Model-Informed Precision Dosing of Tamoxifen.Frontiers in pharmacology · 2020Article
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- The active tamoxifen metabolite endoxifen (4OHNDtam) strongly down-regulates cytokeratin 6 (CK6) in MCF-7 breast cancer cells.PloS one · 2015Article
- Linking estrogen-induced apoptosis with decreases in mortality following long-term adjuvant tamoxifen therapy.Journal of the National Cancer Institute · 2014Article
- Endoxifen and other metabolites of tamoxifen inhibit human hydroxysteroid sulfotransferase 2A1 (hSULT2A1).Drug metabolism and disposition: the biological fate of chemicals · 2014Article
- A review on the role of L-carnitine in the management of tamoxifen side effects in treated women with breast cancer.Tumour biology : the journal of the International Society for Oncodevelopmental Biology and Medicine · 2014Review
- A role for cytochrome b5 in the In vivo disposition of anticancer and cytochrome P450 probe drugs in mice.Drug metabolism and disposition: the biological fate of chemicals · 2014Article
- PharmGKB summary: tamoxifen pathway, pharmacokinetics.Pharmacogenetics and genomics · 2013Review
- MEK1/2 inhibition suppresses tamoxifen toxicity on CNS glial progenitor cells.The Journal of neuroscience : the official journal of the Society for Neuroscience · 2013Article
- Serum concentrations of tamoxifen and its metabolites increase with age during steady-state treatment.Breast cancer research and treatment · 2013Article
Corrections and comments
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Authors and funding
8 authors at 5 institutions in 2 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Tamoxifen dosage is based on the one-dose-fits-all approach. The anticancer effect of tamoxifen is believed to be due to the metabolites, 4-hydroxytamoxifen (4OHtam), and 4-hydroxy-N-desmethyltamoxifen (4OHNDtam/endoxifen). These demethylated metabolites of tamoxifen have been associated with its side effects, whereas the effect mediated by tamoxifen-N-oxide (tamNox) is still poorly understood. Our objective was to improve the therapeutic index of tamoxifen by personalizing its dosage and maintaining serum tamoxifen metabolite concentrations within a target range. We examined the levels of tamoxifen, 4OHtam, 4OHNDtam, N-desmethyltamoxifen (NDtam), N-desdimethyltamoxifen (NDDtam), and tamNox in serum and in breast tumors specimens of 115 patients treated with 1, 5 or 20 mg/day of tamoxifen for 4 weeks before surgery in a randomized trial. Furthermore, the metabolism of tamNox in MCF-7 breast cancer cells was also studied. The concentrations of tamoxifen and its metabolites in tumor tissues were significantly correlated to their serum levels. Tumor tissue levels were 5-10 times higher than those measured in serum, with the exception of tamNox. In MCF-7 cells, tamNox was converted back to tamoxifen. In contrast to the tissue distribution of tamNox, the concentrations of 4OHtam and 4OHNDtam in tumor tissues corresponded to their serum levels. The results suggest that implementation of therapeutic drug monitoring may improve the therapeutic index of tamoxifen. Furthermore, the tissue distribution of tamNox deviated from that of the other tamoxifen metabolites.
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