Significant effect of polymorphisms in CYP2D6 and ABCC2 on clinical outcomes of adjuvant tamoxifen therapy for breast cancer patients.

Journal of Clinical Oncology : Official Journal of the American Society of Clinical Oncology
Kazuma KiyotaniHitoshi Zembutsu

Abstract

The clinical efficacy of tamoxifen is suspected to be influenced by the activity of drug-metabolizing enzymes and transporters involved in the formation, metabolism, and elimination of its active forms. We investigated relationships of polymorphisms in transporter genes and CYP2D6 to clinical outcome of patients receiving tamoxifen. We studied 282 patients with hormone receptor-positive, invasive breast cancer receiving tamoxifen monotherapy, including 67 patients who have been previously reported. We investigated the effects of allelic variants of CYP2D6 and haplotype-tagging single nucleotide polymorphisms (tag-SNPs) of ABCB1, ABCC2, and ABCG2 on recurrence-free survival using the Kaplan-Meier method and Cox regression analysis. Plasma concentrations of tamoxifen metabolites were measured in 98 patients receiving tamoxifen 20 mg/d. CYP2D6 variants were significantly associated with shorter recurrence-free survival (P = .000036; hazard ratio [HR] = 9.52; 95% CI, 2.79 to 32.45 in patients with two variant alleles v patients without variant alleles). Among 51 tag-SNPs in transporter genes, a significant association was found at rs3740065 in ABCC2 (P = .00017; HR = 10.64; 95% CI, 1.44 to 78.88 in patients with AA v GG genotypes)....Continue Reading

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Citations

Aug 12, 2010·European Journal of Clinical Pharmacology·Kazuma KiyotaniHiroshi Yamazaki
Oct 27, 2012·Cancer Chemotherapy and Pharmacology·Andreas TrojanWolfgang Joechle
May 29, 2013·Cancer Chemotherapy and Pharmacology·Zhiyu ZengXue Qin
Jun 13, 2012·Wiener medizinische Wochenschrift·Ariana E Huber-WechselbergerElisabeth Haschke-Becher
May 11, 2010·Breast Cancer Research and Treatment·Bostjan Seruga, Eitan Amir
Sep 3, 2010·Breast Cancer Research and Treatment·Alastair M ThompsonWilliam G Newman
Sep 29, 2011·Breast Cancer Research and Treatment·Kazuma KiyotaniHitoshi Zembutsu
May 21, 2013·Breast Cancer Research and Treatment·Jennifer KarleAnne C Regierer
Oct 12, 2011·Pathology Oncology Research : POR·Adam MaciejczykPaweł Surowiak
Nov 16, 2012·Journal of Human Genetics·Ryo TakataYusuke Nakamura
Mar 20, 2013·Annals of Oncology : Official Journal of the European Society for Medical Oncology·L WengUNKNOWN Consortium on Breast Cancer Pharmacogenomics (COBRA)
Feb 18, 2011·Journal of the National Cancer Institute·Timothy L LashStephen Hamilton-Dutoit
Jun 25, 2010·Pharmacogenetics and Genomics·Kazuma KiyotaniHitoshi Zembutsu
Jan 14, 2011·Annual Review of Medicine·Michaela J Higgins, Vered Stearns
Sep 2, 2011·Clinical Cancer Research : an Official Journal of the American Association for Cancer Research·Matthew P GoetzMatthew M Ames
Sep 12, 2012·Breast Cancer Research : BCR·Leen SasSteven J Van Laere
Jul 20, 2011·Journal of Clinical Oncology : Official Journal of the American Society of Clinical Oncology·William J IrvinLisa A Carey
Apr 26, 2012·The Oncologist·Daniel L HertzWilliam J Irvin
Nov 2, 2011·Drug Metabolism and Pharmacokinetics·Kazuma KiyotaniHitoshi Zembutsu
Feb 27, 2013·Pharmacogenomics·Vid Mlakar, Janja Marc
Apr 30, 2014·Archives of Toxicology·Márton JaniPéter Krajcsi
Apr 28, 2012·Journal of the American Medical Informatics Association : JAMIA·Casey Lynnette OverbyIra J Kalet
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