CYP2D6 Polymorphisms and Response to Tamoxifen

Breast cancer patients with genotypes corresponding to normal CYP2D6 enzyme activity achieved better outcomes than those with diminished or no activity.

Endoxifene, one of two active metabolites that mediate tamoxifen's therapeutic effects, is formed through the action of the CYP2D6 enzyme. Several polymorphisms of the CYP2D6 gene that influence the enzyme's activity and, therefore, endoxifene levels, have been indentified. However, studies designed to uncover the link between patient response to tamoxifen and CYP2D6 enzyme activity (or CYP2D6 genotype) have yielded inconsistent results, perhaps as a result of limited sample sizes. By generating a study of sufficient power, investigators from Germany and the U.S. attempted to more definitively evaluate tamoxifen efficacy in relation to patients' CYP2D6 genotypes.

Data were collected both retrospectively and prospectively in 1325 patients who…

Reviewing Author

Virginia Kaklamani, MD, DSc