CYP2D6 and Endoxifen in Tamoxifen Therapy: A Tribute to David A. Flockhart

Clin Pharmacol Ther. 2018 May;103(5):755-757. doi: 10.1002/cpt.1039. Epub 2018 Feb 23.

Abstract

This issue of Clinical Pharmacology & Therapeutics (CPT) includes the Clinical Pharmacogenetics Implementation Consortium (CPIC) guideline for using CYP2D6 genotyping to guide tamoxifen therapy for breast cancer patients. CYP2D6 metabolizes tamoxifen to its more active metabolite, endoxifen, and patients with reduced CYP2D6 activity have reduced circulating endoxifen concentrations. In this associated commentary, we recognize and honor the late Dr. David Flockhart, who began the research and made early fundamental discoveries on tamoxifen that have now resulted in this guideline.

MeSH terms

  • Antineoplastic Agents, Hormonal / adverse effects
  • Antineoplastic Agents, Hormonal / therapeutic use
  • Breast Neoplasms / drug therapy*
  • Breast Neoplasms / genetics*
  • Clinical Trials, Phase III as Topic
  • Cytochrome P-450 CYP2D6 / genetics*
  • Female
  • Genotype
  • Humans
  • Middle Aged
  • Pharmacogenetics / methods
  • Prospective Studies
  • Randomized Controlled Trials as Topic
  • Retrospective Studies
  • Tamoxifen / adverse effects*
  • Tamoxifen / analogs & derivatives*
  • Tamoxifen / therapeutic use*

Substances

  • Antineoplastic Agents, Hormonal
  • Tamoxifen
  • 4-hydroxy-N-desmethyltamoxifen
  • Cytochrome P-450 CYP2D6