Effect of CYP2C19 and CYP2D6 genotype on tamoxifen treatment outcome indicates endogenous and exogenous interplay

被引：10

作者：

Sim, Sarah ^{[1
]}

Lovrot, John ^{[2
]}

Lindh, Jonatan D. ^{[3
]}

Bergh, Jonas ^{[2
,4
]}

Xie, Hanjing ^{[2
,4
,5
]}

机构：

[1] Karolinska Inst, Dept Physiol & Pharmacol, SE-17176 Stockholm, Sweden

[2] Karolinska Inst, Dept Oncol & Pathol, SE-17176 Stockholm, Sweden

[3] Karolinska Univ Hosp, Dept Clin Pharmacol, SE-14186 Stockholm, Sweden

[4] Karolinska Univ Hosp, Dept Clin Oncol, SE-17176 Stockholm, Sweden

[5] Capio St Gorans Hosp, Dept Oncol, SE-11281 Stockholm, Sweden

来源：

PHARMACOGENOMICS | 2018年 / 19卷 / 13期

关键词：

CYP2C19; CYP2D6; tamoxifen; BREAST-CANCER PATIENTS; HUMAN CYTOCHROME-P450 ENZYMES; ADJUVANT TAMOXIFEN; ESTROGEN-RECEPTOR; GENETIC POLYMORPHISMS; IN-VITRO; METABOLISM; CYP2C19-ASTERISK-2; 17-BETA-ESTRADIOL; PHARMACOKINETICS;

D O I：

10.2217/pgs-2018-0089

中图分类号：

R9 [药学];

学科分类号：

1007 ;

摘要：

Aim: We investigated the interaction of CYP2C19 and CYP2D6 genotype on clinical outcome in tamoxifen-treated breast cancer patients. Materials & methods: A cohort of 306 patients on tamoxifen treatment for a minimum of 1 year were employed to analyze the effect of genotype-predicted phenotype on relapse-free survival. Results & conclusion: We show that the group with worst outcome and highest risk of relapse is that of 2C19.-2D6. (hazard ratio: 2.94), when adjusting for age, Nottingham prognostic index and adjuvant chemotherapy. Furthermore, the effect of 2C19.-2D6. genotype-predicted phenotype is greatly enhanced in premenopausal patients (hazard ratio: 21.08). We hypothesize that poor bioactivation of tamoxifen in patients with low CYP2D6 activity and high CYP2C19 metabolism represents a tamoxifen-treated patient group that has the worst clinical outcome.

引用

页码：1027 / 1037

页数：11

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