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

Pharmacogenomics
Sarah SimHanjing Xie

Abstract

We investigated the interaction of CYP2C19 and CYP2D6 genotype on clinical outcome in tamoxifen-treated breast cancer patients. 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. 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.

References

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Citations

Jun 27, 2020·Personalized Medicine·Rangel-Méndez Jorge-AarónMoo-Puc Rosa Esther
Dec 16, 2020·Expert Opinion on Drug Metabolism & Toxicology·Ondřej SlanařMartin Šíma
Mar 2, 2021·Pharmacogenomics and Personalized Medicine·Chiara JeizinerHenriette E Meyer Zu Schwabedissen
May 18, 2021·Clinical Pharmacology and Therapeutics·Yitian Zhou, Volker M Lauschke

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Methods Mentioned

BETA
genotyping
hormone-replacement therapy

Software Mentioned

R
coxph

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