The Discriminatory Value of CYP2D6 Genotyping in Predicting the Dextromethorphan/Dextrorphan Phenotype in Women with Breast Cancer.

Breast Care
Andreas TrojanWolfgang Joechle

Abstract

BACKGROUND: The growth inhibitory effect of tamoxifen is used for the treatment of breast cancer. Tamoxifen efficacy is mediated by its biotransformation, predominantly via the cytochrome P450 2D6 (CYP2D6) isoenzyme, to the active metabolite endoxifen. We investigated the relationship of CYP2D6 genotypes to the metabolism of dextromethorphan (DM), which is frequently used as a surrogate marker for the formation of endoxifen. METHODS: The CYP2D6 genotype was determined by polymerase chain reaction (PCR) in previously untreated patients with hormone receptor-positive invasive breast cancer considered to receive antihormonal therapy. The DM/dextrorphan (DX) urinary excretion ratios were obtained in a subset of patients by high-pressure liquid chromatography (HPLC)-mediated urine analysis after intake of 25 mg DM. The relationships of genotype and corresponding phenotype were statistically analyzed for association. RESULTS: From 151 patients predicted based on their genotype data for the 'traditional' CYP2D6 phenotype classes poor, intermediate, extensive and ultrarapid, 83 patients were examined for their DM/DX urinary ratios. The genotype-based poor metabolizer status correlated with the DM/DX ratios, whereas the intermediate, ...Continue Reading

References

Jan 1, 1990·European Journal of Cancer : Official Journal for European Organization for Research and Treatment of Cancer (EORTC) [and] European Association for Cancer Research (EACR)·S M Langan-FaheyV C Jordan
Mar 29, 1996·Journal of Chromatography. B, Biomedical Applications·J DucharmeI W Wainer
Apr 28, 2004·Breast Cancer Research and Treatment·Michael D JohnsonTodd C Skaar
Jan 6, 2005·Journal of the National Cancer Institute·Yan JinDavid A Flockhart
Dec 20, 2005·Journal of Clinical Oncology : Official Journal of the American Society of Clinical Oncology·Matthew P GoetzJames N Ingle
Nov 23, 2006·Breast Cancer Research and Treatment·Matthew P GoetzJames N Ingle
Feb 16, 2007·Clinical Pharmacology and Therapeutics·M J BlakeJ S Leeder
Jun 2, 2007·Breast Cancer Research and Treatment·Joanne E MortimerUNKNOWN WHEL Study Group
Oct 20, 2007·Annals of Oncology : Official Journal of the European Society for Medical Oncology·J GjerdeE A Lien
Nov 1, 2007·Clinical Pharmacology and Therapeutics·A GaedigkJ S Leeder
Apr 15, 2008·Annals of Oncology : Official Journal of the European Society for Medical Oncology·Y XuY Xie
Sep 17, 2008·Clinical Cancer Research : an Official Journal of the American Association for Cancer Research·William G NewmanD Gareth Evans
Feb 4, 2009·Breast Cancer Research and Treatment·T Ramón y CajalM Baiget
Feb 4, 2009·Breast Cancer Research and Treatment·Monique J BijlLoes E Visser
May 8, 2009·The Pharmacogenomics Journal·J M RaeUNKNOWN COBRA investigators
Jul 4, 2009·Clinical Chemistry·Hiltrud BrauchMatthias Schwab
Aug 4, 2009·The Lancet Oncology·Timothy L LashStephen Hamilton-Dutoit
Oct 8, 2009·JAMA : the Journal of the American Medical Association·Werner SchrothHiltrud Brauch
Feb 4, 2010·Journal of Clinical Oncology : Official Journal of the American Society of Clinical Oncology·Kazuma KiyotaniHitoshi Zembutsu
Sep 3, 2010·Breast Cancer Research and Treatment·Alastair M ThompsonWilliam G Newman
Jul 20, 2011·Journal of Clinical Oncology : Official Journal of the American Society of Clinical Oncology·Anne-Joy M de GraanRon H J Mathijssen

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Citations

Oct 27, 2012·Cancer Chemotherapy and Pharmacology·Andreas TrojanWolfgang Joechle
Jun 11, 2014·British Journal of Clinical Pharmacology·Rashmi R Shah, Robert L Smith
Feb 7, 2015·The Journal of Pharmacology and Experimental Therapeutics·Yasmin SchmidMatthias E Liechti

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