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01.06.2012 | review | Ausgabe 11-12/2012

Wiener Medizinische Wochenschrift 11-12/2012

Impact of CYP2D6 polymorphism on tamoxifen therapy: where are we?

Zeitschrift:
Wiener Medizinische Wochenschrift > Ausgabe 11-12/2012
Autoren:
PhD Ariana E. Huber-Wechselberger, MD Paul Niedetzky, Irene Aigner, MD Elisabeth Haschke-Becher

Summary

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.

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