ABSTRACT
Tamoxifen is an antagonist of the estrogen receptor (ER) in breast tissue via its active metabolite, hydroxytamoxifen or endoxifen. It has mainly been used to treat or prevent the recurrence of ER–positive breast cancers in patients. This chapter describes critical issues in pharmacogenomics studies and summarizes the results of the association of CYP2D6 genotype with tamoxifen efficacy. Tamoxifen is metabolized in the liver in human body to several metabolites that exhibit a range of pharmacologic activities. In the recent meta-analysis result of data from 4973 tamoxifen-treated patients, the International Tamoxifen Pharmacogenomics Consortium reports that CYP2D6 poor metabolizer status is associated with poorer invasive disease–free survival (IDFS) using strict inclusion criteria. CYP2C9 and VKORC1 have been associated with this interindividual variation of the appropriate dose of warfarin leading to genotype-guided dosing tables in warfarin labeling.
