Clinical Pharmacogenetics Implementation Consortium (CPIC) Guideline for CYP2D6 and Tamoxifen Therapy

Matthew P Goetz; Katrin Sangkuhl; Henk-Jan Guchelaar; Matthias Schwab; Michael Province; Michelle Whirl-Carrillo; W Fraser Symmans; Howard L McLeod; Mark J Ratain; Hitoshi Zembutsu; Andrea Gaedigk; Ron H van Schaik; James N Ingle; Kelly E Caudle; Teri E Klein

doi:10.1002/cpt.1007

Clinical Pharmacogenetics Implementation Consortium (CPIC) Guideline for CYP2D6 and Tamoxifen Therapy

Clin Pharmacol Ther. 2018 May;103(5):770-777. doi: 10.1002/cpt.1007. Epub 2018 Jan 31.

Authors

Matthew P Goetz¹, Katrin Sangkuhl², Henk-Jan Guchelaar³, Matthias Schwab^{4

5

6}, Michael Province⁷, Michelle Whirl-Carrillo², W Fraser Symmans⁸, Howard L McLeod⁹, Mark J Ratain¹⁰, Hitoshi Zembutsu¹¹, Andrea Gaedigk¹², Ron H van Schaik^{13

14}, James N Ingle¹, Kelly E Caudle¹⁵, Teri E Klein²

Affiliations

¹ Department of Oncology, Department of Molecular Pharmacology and Experimental Therapeutics, Mayo Clinic, Rochester, Minnesota, USA.
² Department of Biomedical Data Science, Stanford University, Stanford, California, USA.
³ Department of Clinical Pharmacy and Toxicology, Leiden University Medical Center, Leiden, The Netherlands.
⁴ Dr Margarete Fischer-Bosch-Institute of Clinical Pharmacology, Stuttgart, Germany.
⁵ Department of Clinical Pharmacology, University Hospital, Tuebingen, Germany.
⁶ Department of Pharmacy and Biochemistry, University of Tuebingen, Tuebingen, Germany.
⁷ Division of Statistical Genomics, Washington University School of Medicine, St. Louis, Missouri, USA.
⁸ Department of Pathology, University of Texas MD Anderson Cancer Center, Houston, Texas, USA.
⁹ Moffitt Cancer Center, Tampa, Florida, USA.
¹⁰ Center for Personalized Therapeutics, University of Chicago, Chicago, Illinois, USA.
¹¹ Division of Human Genetics, National Cancer Center, Research Institute, Tokyo, Japan.
¹² Division of Clinical Pharmacology, Toxicology & Therapeutic Innovation, Children's Mercy Kansas City and Department of Pediatrics, University of Missouri-Kansas City, Kansas City, Missouri, USA.
¹³ International Expertcenter Pharmacogenetics, Dept Clinical Chemistry, Erasmus MC, Rotterdam, The Netherlands.
¹⁴ LKCH UMC Utrecht, The Netherlands.
¹⁵ Department of Pharmaceutical Sciences, St. Jude Children's Research Hospital, Memphis, Tennessee, USA.

Abstract

Tamoxifen is biotransformed by CYP2D6 to 4-hydroxytamoxifen and 4-hydroxy N-desmethyl tamoxifen (endoxifen), both with greater antiestrogenic potency than the parent drug. Patients with certain CYP2D6 genetic polymorphisms and patients who receive strong CYP2D6 inhibitors exhibit lower endoxifen concentrations and a higher risk of disease recurrence in some studies of tamoxifen adjuvant therapy of early breast cancer. We summarize evidence from the literature and provide therapeutic recommendations for tamoxifen based on CYP2D6 genotype.

Publication types

Research Support, N.I.H., Extramural
Research Support, Non-U.S. Gov't

MeSH terms

Antineoplastic Agents, Hormonal / therapeutic use
Breast Neoplasms / drug therapy*
Breast Neoplasms / genetics*
Cytochrome P-450 CYP2D6 / genetics*
Cytochrome P-450 CYP2D6 Inhibitors / therapeutic use
Female
Genotype
Humans
Neoplasm Recurrence, Local / genetics
Pharmacogenetics / legislation & jurisprudence*
Tamoxifen / analogs & derivatives
Tamoxifen / metabolism
Tamoxifen / therapeutic use*

Substances

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

Abstract

Publication types

MeSH terms

Substances

Grants and funding