Impact of CYP2D6 polymorphism on tamoxifen therapy: where are we?
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.
Competence Center of Molecular Biology and Genetics, Elisabethinen Hospital Linz GmbH, Fadingerstrasse 1, 4020, Linz, Austria. ariana.huber-wechselberger@elisabethinen.or.at
Ariana E
AE
Huber-Wechselberger
Paul
P
Niedetzky
Irene
I
Aigner
Elisabeth
E
Haschke-Becher
D000483:Alleles; D018931:Antineoplastic Agents, Hormonal / Q000493:pharmacokinetics / Q000627:therapeutic use*; D001943:Breast Neoplasms / Q000188:drug therapy* / Q000208:ethnology / Q000235:genetics*; D015331:Cohort Studies; D019389:Cytochrome P-450 CYP2D6 / Q000235:genetics*; D005006:Ethnicity / Q000235:genetics; D005260:Female; D017353:Gene Deletion; D005787:Gene Frequency / Q000235:genetics; D005820:Genetic Testing; D005838:Genotype; D006801:Humans; D009376:Neoplasms, Hormone-Dependent / Q000188:drug therapy* / Q000235:genetics*; D011110:Polymorphism, Genetic / Q000235:genetics*; D013629:Tamoxifen / Q000493:pharmacokinetics / Q000627:therapeutic use*; D016896:Treatment Outcome
D018931:Antineoplastic Agents, Hormonal; D013629:Tamoxifen; D019389:Cytochrome P-450 CYP2D6