1. ¹Department of Oncology, Mayo Clinic College of Medicine, Rochester, Minnesota, USA
2. ²Department of Medicine, Mayo Clinic College of Medicine, Rochester, Minnesota, USA
3. ³Department of Molecular Pharmacology and Experimental Therapeutics, Mayo Clinic College of Medicine, Rochester, Minnesota, USA

Correspondence: MP Goetz, (goetz.matthew@mayo.edu)

Abstract

Tamoxifen continues to be a standard endocrine therapy for the prevention and treatment of estrogen receptor (ER)-positive breast cancer. Tamoxifen can be considered a classic "pro-drug," requiring metabolic activation to elicit pharmacological activity. CYP2D6 is the rate-limiting enzyme catalyzing the conversion of tamoxifen into metabolites with significantly greater affinity for the ER and greater ability to inhibit cell proliferation. Both genetic and environmental (drug-induced) factors that alter CYP2D6 enzyme activity directly affect the concentrations of the active tamoxifen metabolites and the outcomes of patients receiving adjuvant tamoxifen. The a priori knowledge of the pharmacogenetic variation known to abrogate CYP2D6 enzyme activity may provide a means by which the hormonal therapy of breast cancer can be individualized.