Is CYP2D6 genotyping for tamoxifen (Nolvadex) sensitivity before use of the drug beneficial?

The significance of CYP2D6 genotyping and tamoxifen relates to the metabolite endoxifen, which is extremely important to the overall anticancer effects of tamoxifen (Clinical Oncology News. 2011;06:02). Endoxifen is predominantly formed by the CYP2D6 enzyme-mediated oxidation of N-desmethyltamoxifen. There has been controversy as to whether or not women receiving tamoxifen who either carry genetic variants associated with low or absent CYP2D6 activity, or who receive concomitant medications known to inhibit CYP2D6 activity have significantly lower levels of endoxifen, worse relapse-free time, and worse disease-free survival.

Recent data from retrospective analyses of the ATAC study, which included 9,366 postmenopausal women with invasive breast cancer, that focused on subsets of 615 of 3,125 women who had received anastrozole and 588 of 3,116 women who had received tamoxifen demonstrated no evidence that CYP2D6 genotyping is an effective predictor of recurrence in either arm. The study also demonstrated that there was no strong evidence for avoiding CYP2D6 inhibitors such as fluoxetine, paroxetine, quinidine, and buproprion.

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The lack of standardization for CYP2D6 phenotype testing and variations of use with concomitant CYP2D6 inhibitors allows for weaknesses in the validity of this information. Overall consensus that remains from the recent San Antonio Breast Cancer Symposium thought leaders is that there are no data to warrant routine genotype testing for postmenopausal women taking tamoxifen; however, there should still be some degree of caution and avoidance of potent CYP2D6 inhibitors in women treated with tamoxifen. — Jiajoyce R. Conway, DNP, FNP-BC, NP-C ONA