The Impact of CYP2D6 Genotyping on Tamoxifen Treatment

Roberta Ferraldeschi, William G Newman, Roberta Ferraldeschi, William G Newman

Abstract

Tamoxifen remains a cornerstone of treatment for patients with oestrogen-receptor-positive breast cancer. Tamoxifen efficacy depends on the biotransformation, predominantly via the cytochrome P450 2D6 (CYP2D6) isoform, to the active metabolite endoxifen. Both genetic and environmental (drug-induced) factors may alter CYP2D6 enzyme activity directly affecting the concentrations of active tamoxifen metabolites. Several studies suggest that germline genetic variants in CYP2D6 influence the clinical outcomes of patients treated with adjuvant tamoxifen. Here, we review the existing data relating CYP2D6 genotypes to tamoxifen efficacy.

Keywords: CYP2D6 genotyping; breast cancer; tamoxifen.

Figures

Figure 1
Figure 1
Tamoxifen metabolism in the liver. CYP3A4 and CYP3A5 are the major enzymes responsible for N-demethylation, whereas 4-hydroxylation is predominantly mediated by CYP2D6. Reprinted with permission. © 2009 PharmGKB. All rights reserved.

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