Loss of Heterozygosity at the CYP2D6 Locus in Breast Cancer: Implications for Tamoxifen Pharmacogenetic Studies

Journal of the National Cancer Institute – Loss of functional genetic polymorphisms in CYP2D6 lead to the absence of functional CYP2D6 protein in approximately 5% to 10% of whites (people of European ancestry) and 1% to 2% of those of Asian and African ancestry. In the literature, these are commonly referred to as CYP2D6–poor metabolizers (PMs). The first study to report an association between CYP2D6polymorphisms and endoxifen plasma concentration was published in 2003 and showed that CYP2D6 PMs exhibited lower endoxifen plasma concentrations than those with functional CYP2D6 enzyme. The results from this study served as an impetus to investigate the influence of CYP2D6 gene variation on clinical outcomes with tamoxifen.