Please use this identifier to cite or link to this item: https://hdl.handle.net/2440/58681
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dc.contributor.authorBrauch, H.-
dc.contributor.authorMurdter, T.-
dc.contributor.authorEichelbaum, M.-
dc.contributor.authorSchwab, M.-
dc.date.issued2009-
dc.identifier.citationClinical Chemistry (Washington, DC): international journal of molecular diagnostics and laboratory medicine, 2009; 55(10):1770-1782-
dc.identifier.issn0009-9147-
dc.identifier.issn1530-8561-
dc.identifier.urihttp://hdl.handle.net/2440/58681-
dc.description.abstractBackground: Tamoxifen is a standard endocrine therapy for the prevention and treatment of steroid hormone receptor–positive breast cancer. Content: Tamoxifen requires enzymatic activation by cytochrome P450 (CYP) enzymes for the formation of active metabolites 4-hydroxytamoxifen and endoxifen. As compared with the parent drug, both metabolites have an approximately 100-fold greater affinity for the estrogen receptor and the ability to inhibit cell proliferation. The polymorphic CYP2D6 is the key enzyme in this biotransformation, and recent mechanistic, pharmacologic, and clinical evidence suggests that genetic variants and drug interaction by CYP2D6 inhibitors influence the plasma concentrations of active tamoxifen metabolites and the outcomes of tamoxifen-treated patients. In particular, nonfunctional (poor metabolizer) and severely impaired (intermediate metabolizer) CYP2D6 alleles are associated with higher recurrence rates. Summary: Accordingly, CYP2D6 (cytochrome P450, family 2, subfamily D, polypeptide 6) genotyping before treatment to predict metabolizer status may open new avenues for individualizing endocrine treatment, with the maximum benefit being expected for extensive metabolizers. Moreover, strong CYP2D6 inhibitors such as the selective serotonin reuptake inhibitors paroxetine and fluoxetine, which are used to treat hot flashes, should be avoided because they severely impair formation of the active metabolites.-
dc.description.statementofresponsibilityHiltrud Brauch, Thomas E. Mürdter, Michel Eichelbaum and Matthias Schwab-
dc.language.isoen-
dc.publisherAmer Assoc Clinical Chemistry-
dc.rights© 2009 American Association for Clinical Chemistry, Inc.-
dc.source.urihttp://dx.doi.org/10.1373/clinchem.2008.121756-
dc.subjectHumans-
dc.subjectBreast Neoplasms-
dc.subjectNeoplasms, Hormone-Dependent-
dc.subjectTamoxifen-
dc.subjectAryl Hydrocarbon Hydroxylases-
dc.subjectCytochrome P-450 CYP2D6-
dc.subjectOxidoreductases, N-Demethylating-
dc.subjectAntineoplastic Agents, Hormonal-
dc.subjectPharmacogenetics-
dc.subjectFemale-
dc.subjectCytochrome P-450 CYP3A-
dc.subjectGenetic Variation-
dc.subjectCytochrome P-450 CYP2B6-
dc.subjectCytochrome P-450 CYP2C9-
dc.subjectCytochrome P-450 CYP2C19-
dc.titlePharmacogenomics of Tamoxifen Therapy-
dc.typeJournal article-
dc.identifier.doi10.1373/clinchem.2008.121756-
pubs.publication-statusPublished-
Appears in Collections:Aurora harvest
Pharmacology publications

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