Pharmacogenomics toward personalized tamoxifen therapy for breast cancer

Abstract

Tamoxifen has been used not only for the treatment or prevention of recurrence in patients with estrogen receptor positive breast cancers but also for recurrent breast cancer. Because CYP2D6 is known to be an important enzyme responsible for the generation of the potent tamoxifen metabolite, ‘endoxifen’, lots of studies reported that genetic variation which reduced its enzyme activity were associated with poor clinical outcome of breast cancer patients treated with tamoxifen. However, there are some discrepant reports questioning the association between CYP2D6 genotype and clinical outcome after tamoxifen therapy. Dose-adjustment study of tamoxifen based on CYP2D6 genotypes provides the evidence that dose adjustment is useful for the patients carrying reduced or null allele of CYP2D6 to maintain the effective endoxifen level. This review describes critical issues in pharmacogenomic studies as well as summarizes the results of the association of CYP2D6 genotype with tamoxifen efficacy.