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Nat Rev Cancer. 2009 Aug;9(8):576-86. doi: 10.1038/nrc2683.

CYP2D6 and tamoxifen: DNA matters in breast cancer.

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  • 1UNC Institute for Pharmacogenomics and Individualized Therapy, Division of Pharmacotherapy and Experimental Therapeutics, University of North Carolina, Chapel Hill, 27599, North Carolina, USA.

Abstract

Tamoxifen is the most widely used anti-oestrogen for the treatment of hormone-dependent breast cancer. The pharmacological activity of tamoxifen is dependent on its conversion by the hepatic drug-metabolizing enzyme cytochrome P450 2D6 (CYP2D6) to its abundant metabolite, endoxifen. Patients with reduced CYP2D6 activity, as a result of either their genotype or induction by the co-administration of drugs that inhibit CYP2D6 function, produce little endoxifen and seem to derive inferior therapeutic benefit from tamoxifen. Here we review the existing data that relate CYP2D6 genotypes to response to tamoxifen and discuss whether the analysis of the CYP2D6 genotype might be an early example of a pharmacogenetic tool for optimizing breast cancer therapy.

PMID:
19629072
[PubMed - indexed for MEDLINE]
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