Please use this identifier to cite or link to this item: http://hdl.handle.net/2440/53965
Citations
Scopus Web of ScienceĀ® Altmetric
?
?
Type: Journal article
Title: Clinical relevance of CYP2D6 genetics for tamoxifen response in breast cancer
Author: Brauch, H.
Schroth, W.
Eichelbaum, M.
Schwab, M.
Harbeck, N.
Citation: Breast Care, 2008; 3(1):43-50
Publisher: Karger
Issue Date: 2008
ISSN: 1661-3791
1661-3805
Statement of
Responsibility: 
Hiltrud Brauch, Werner Schroth, Michel Eichelbaum, Matthias Schwab and Nadia Harbeck, in cooperation with the AGO TRAFO Comission.
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 co-medication.
Keywords: Breast cancer; Tamoxifen; Prediction of treatment outcome; CYP2D6 metabolism; Poor metabolizer
RMID: 0020084527
DOI: 10.1159/000114642
Appears in Collections:Pharmacology publications

Files in This Item:
There are no files associated with this item.


Items in DSpace are protected by copyright, with all rights reserved, unless otherwise indicated.