Clinical implications of CYP2D6 genotyping in tamoxifen treatment for breast cancer

Clinical Cancer Research : an Official Journal of the American Association for Cancer Research
Vincent O DezentjéHans Gelderblom

Abstract

In October 2006 the Food and Drug Administration recommended an update in the tamoxifen label to reflect the increased risk of recurrence in breast cancer patients who are cytochrome P450 2D6 (CYP2D6) poor metabolizers. This recommendation was based on only a few studies at that time. More clinical studies addressing the relation between the CYP2D6 genotype and tamoxifen efficacy have been published since, mostly describing Caucasian populations in the adjuvant treatment setting. An updated analysis of the literature is presented. Furthermore, the possibility to implement CYP2D6 genotyping in clinical practice is evaluated by analyzing the results of six studies on mainly Caucasian patients using adjuvant tamoxifen. Three studies were consistent with the FDA advice, but the three other studies showed contradictory results. Although some of the published criticism on the negative studies is justified, this does not imply that these results should be discarded. The reviewed literature is put in perspective acknowledging the limiting effect of Mendelian randomization on confounding and the limitations of the various study designs. The current accumulation of data showing worse clinical outcome in patients with decreased CYP2D6 met...Continue Reading

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