Association Study Between CYP2D6Polymorphism And Plasma Concentration Of An Activity Metabolite Of Tamoxifen: Endoxifen

Objective: To study the association between polymorphism of CYP2D6andsteady-state plasma concentration of Endoxifen（an activity metabolite oftamoxifen）in premenopausal ER-positive breast cancer patients receivingadjuvant tamoxifen（TAM）treatment and explore the association between thepolymorphism of CYP2D6and the occurrence of drug side effects in the sameparticipants, in order to provide a basis from genetic pharmacology forpredicting therapeutic benefits of TAM, for screening patients who are likely tobenefit from TAM adjuvant therapy, for avoiding excessive use of TAM andfurther achieving the objective of rational use of TAM in the adjuvant endocrinetherapy for breast cancer.Methods: Tetra-primer ARMS PCR was used to detect the genotypes ofCYP2D6in57participants, liquid chromatography tandem mass spectrometry（LC-MS/MS）was used to detect the plasma concentrations of TAM and itsactivity metabolite Endoxifen, and we marked the patients who experiencingthe side effects of TAM from current medication.Results:1. Of the57cases，9（15.8%）were wild genotype，25（43.9%）were CYP2D6*1/*10genotype and23（40.3%）were CYP2D6*10/*10genotype.The allelic frequency was consistent with Hardy-Weinberg equilibrium;2. A.The steady-state plasma concentration of Endoxifen in group*10/*10andgroup*1/*10were lower than that in group*1/*1（P＜0.01）, but there was no significant difference between group*10/*10and group*1/*10（P＞0.05）. B.There was no statistical significant difference in the plasma concentration ofTAM among all group（sP＞0.05）.3. The occurrence of self-reported TAM sideeffects in group*1/*1was less than that in other two groups（P＜0.05）.Conclusions:1. The CYP2D6polymorphism has an impact on the plasmaconcentration of Endoxifen.2. The occurrence of TAM-related side effects arerelevant to CYP2D6polymorphism.3. CYP2D6genotypes can help screeningpatients who may benefit from treatment of TAM, so that those patients whomay not benefit from the initial treatment of TAM could receive other effectivetherapy, and it can also help avoiding excessive use of TAM that causeundesirable side effects and waste of drug resources. According to the CYP2D6genotype, it is feasible to guide the rational application of personalizedmedicine in the treatment of TAM for premenopausal ER-positive breast cancerpatients.