Breast Care
Review Article · Übersichtsarbeit
Clinical Relevance of CYP2D6 Genetics for Tamoxifen Response in Breast CancerBrauch H.a · Schroth W.a · Eichelbaum M.a · Schwab M.a,b · Harbeck N.ca Dr. Margarete Fischer Bosch Institute of Clinical Pharmacology Stuttgart and University Tübingen, bDepartment of Clinical Pharmacology, University Hospital Tübingen, c Department of Obstetrics and Gynecology, Technical University of Munich, Germany, dArbeitsgemeinschaft Gynäkologische Onkologie (AGO), Kommission für Translationale Forschung
Prof. Dr. Hiltrud Brauch, Dr. Margarete Fischer-Bosch-Institute für Klinische Pharmakologie, Auerbachstrasse 112, 70376 Stuttgart, Germany, Tel. 0711-8101 3705, Fax -85 92 95, E-mail hiltrud.brauch@ikp-stuttgart.de |
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Abstract
Tamoxifen is a standard endocrine therapy for the prevention and treatment of steroid hormone receptor-positive breast cancer. Tamoxifen requires enzymatic activation by CYP 450 enzymes for the formation of clinically relevant metabolites, 4-OH-tamoxifen and endoxifen, which both have a greater affinity to the estrogen receptor and ability to inhibit cell proliferation when compared to the parent drug. CYP2D6 is the key enzyme in this biotransformation, and recent mechanistic, pharmacologic, and clinical pharmacogenetic evidence suggests that genetic variants and drug interaction by CYP2D6 inhibitors influence plasma concentrations of active tamoxifen metabolites and outcome of patients treated with adjuvant tamoxifen. Particularly, non-functional (poor metabolizer) and severely impaired (intermediate metabolizer) CYP2D6 variants are associated with higher recurrence rates. Accordingly, CYP2D6 genotyping prior to treatment for prediction of metabolizer status and outcome may open new avenues for the individualization of endocrine treatment choice and benefit. Moreover, strong CYP2D6 inhibitors such as the selective serotonin reuptake inhibitor paroxetine should be avoided as comedication.
© 2008 S. Karger AG, Basel
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Article / Publication Details
Published online: February 22, 2008
Issue release date: March 2008
Number of Print Pages: 8
Number of Figures: 3
Number of Tables: 0
ISSN: 1661-3791 (Print)
eISSN: 1661-3805 (Online)
For additional information: https://www.karger.com/BRC
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