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Tamoxifen and CYP2D6 Interactions

CYP2D6 gene testing for personalizing tamoxifen therapy has been a source of confusion and debate for over a decade. In addition to conflicting outcomes data on breast cancer recurrence rates in women with deficient CYP2D6 enzyme activity (i.e., CYP2D6 Intermediate and Poor Metabolizers) treated with tamoxifen, significant controversy exists around the methodology for using tumor cell DNA to estimate the phenotype rather than germline DNA. Excellent commentary on this can be read by accessing this article and reading the open access commentaries.

It is important to note that the National Comprehensive Cancer Network (NCCN) and American Society of Clinical Oncology (ASCO) do not recommend CYP2D6 testing as a tool to determine the optimal adjuvant endocrine strategy. However, both groups do caution about the coadministration of tamoxifen with potent CYP2D6 inhibitors.

See the following articles in for more information on the CYP2D6-tamoxifen controversy:

JAMA. 2009 Oct 7;302(13):1429-36.

J Natl Cancer Inst. 2012 Mar 21;104(6):441-51.

J Natl Cancer Inst. 2012 Mar 21;104(6):452-60.

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