Related Experiment Video
Updated: May 21, 2026

An Integrated Raman Spectroscopy and Mass Spectrometry Platform to Study Single-Cell Drug Uptake, Metabolism, and Effects
Published on: January 9, 2020
Impact of CYP2D6 polymorphism on tamoxifen therapy: where are we?
Ariana E Huber-Wechselberger1, Paul Niedetzky, Irene Aigner
1Competence Center of Molecular Biology and Genetics, Elisabethinen Hospital Linz GmbH, Fadingerstrasse 1, 4020, Linz, Austria. ariana.huber-wechselberger@elisabethinen.or.at
Abstract:
Tamoxifen is a mainstay in the treatment of hormone-receptor sensitive breast cancer. To be effective, it needs conversion into 4-hydroxy-tamoxifen and endoxifen. The key enzyme involved is encoded by the gene CYP2D6 of which several, sometimes population-specific alleles are known. Corresponding enzyme variants may result in poor, intermediate, and extensive metabolization and therefore different steady-state plasma levels of active metabolites. Those are hypothesized to be linked to clinical outcomes of tamoxifen therapy. However, a wealth of mostly retrospective cohort studies came up with conflicting results. Appraisal of these studies is difficult and a metaanalysis impossible due to heterogeneity of patient populations, disease factors, treatment modalities, and measured outcomes. As standardization would not overcome intrinsic limitations of retrospective analyses, prospective trials comparing genotype-guided versus unsighted tamoxifen treatment are required to prove whether routine CYP2D6 genotyping is clinically effective and cost-effective.
Related Concept Videos
Pharmacogenetic Phenotypes: Alterations in Pharmacokinetics, Drug Targets and Biologic Milieu
Pharmacogenetics of Phase I Enzymes: Cytochrome P450 Isozymes
Pharmacogenetics of Drug Targets: β₂-Adrenergic Receptors, Apo E, Thymidylate Synthase
Pharmacogenetics of Drug Metabolism: Overview
Pharmacogenetics of Phase II Enzymes: N-acetyltransferase, Thiopurine S-methyltransferase, UDP-glucuronosyltransferase
Nonlinear Pharmacokinetics: Dependence of Elimination Half-Life and Dose Clearance
A study on guinea pigs examined the...