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    Clin Pharmacol Ther. 2008 Jan;83(1):160-6. Epub 2007 Sep 19.

    Tamoxifen pharmacogenomics: the role of CYP2D6 as a predictor of drug response.

    Goetz MP, Kamal A, Ames MM.

    Source

    Department of Oncology, Mayo Clinic College of Medicine, Rochester, Minnesota, USA. goetz.matthew@mayo.edu

    Abstract

    Tamoxifen continues to be a standard endocrine therapy for the prevention and treatment of estrogen receptor (ER)-positive breast cancer. Tamoxifen can be considered a classic "pro-drug," requiring metabolic activation to elicit pharmacological activity. CYP2D6 is the rate-limiting enzyme catalyzing the conversion of tamoxifen into metabolites with significantly greater affinity for the ER and greater ability to inhibit cell proliferation. Both genetic and environmental (drug-induced) factors that alter CYP2D6 enzyme activity directly affect the concentrations of the active tamoxifen metabolites and the outcomes of patients receiving adjuvant tamoxifen. The a priori knowledge of the pharmacogenetic variation known to abrogate CYP2D6 enzyme activity may provide a means by which the hormonal therapy of breast cancer can be individualized.

    PMID:
    17882159
    [PubMed - indexed for MEDLINE]
    PMCID:
    PMC2752373
    Free PMC Article

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