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    The debate about the extent to which CYP2D6 activity affects tamoxifen efficacy in patients with breast cancer continues, but the plot has thickened considerably since we last discussed this issue on these pages in March 2009. Since then, research papers have continued to appear on both sides of the issue, some suggesting that reduced CYP2D6 activity due to genetics or CYP2D6-inhibiting drugs reduces tamoxifen efficacy, leading to earlier breast cancer relapse and reduced survival, and others failing to find any effect. We also have more evidence that drug interactions involving other tamoxifen metabolic pathways and adenosine triphosphate–binding cassette transporters may also affect tamoxifen efficacy. CYP2D6 Inhibitors CYP2D6 is the most important enzyme in the metabolism of tamoxifen to its primary active metabolite (endoxifen), so it is biologically plausible that the concurrent use of moderate to strong CYP2D6 inhibitors with tamoxifen would inhibit its anticancer effects. Two epidemiological studies published in the past year failed to find any effect of CYP2D6 inhibitors on tamoxifen efficacy, which might reduce tamoxifen bioavailability and increase endoxifen efflux from cancer cells. Theoretically, then, patients with higher P-glycoprotein activity due to genetics or drug therapy would have impaired tamoxifen efficacy. In 1 study, the median time to develop recurrence and metastasis was just 12 months in breast cancer patients with decreased CYP2D6 activity and high P-glycoprotein activity, compared with 48 months in patients with either decreased CYP2D6 or high P-glycoprotein activity alone. So it may be that decreased CYP2D6 activity and increased P-glycoprotein activity can work in concert to impair tamoxifen efficacy. Study Suggests Earlier Research on CYP2D6 Is Flawed can i buy prednisolone over the counter in spain Tamoxifen and CYP2D6 A Contradiction of Data - NCBI - NIH Does CYP2D6 Genotyping have a Role in Guiding Tamoxifen.
     
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