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

doi:10.1002/cpt.1007

Practice Guideline

. 2018 May;103(5):770-777.

doi: 10.1002/cpt.1007. Epub 2018 Jan 31.

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

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.

PMID: 29385237
PMCID: PMC5931215
DOI: 10.1002/cpt.1007

Practice Guideline

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

Matthew P Goetz et al. Clin Pharmacol Ther. 2018 May.

. 2018 May;103(5):770-777.

doi: 10.1002/cpt.1007. Epub 2018 Jan 31.

Authors

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.

PMID: 29385237
PMCID: PMC5931215
DOI: 10.1002/cpt.1007

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.

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Conflict of interest statement

CONFLICT OF INTEREST

A.G. is a paid consultant of Millennium Health.

Figures

**Figure 1**
Tamoxifen Pathway, Pharmacokinetics (57). Permission has been given by PharmGKB and Stanford to use figure.

See this image and copyright information in PMC

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References

1. PharmGKB. [Accessed September 16 2016];Gene Reference Materials for CYP2D6. < https://www.pharmgkb.org/page/cyp2d6RefMaterials>.
1. Crews KR, et al. Clinical Pharmacogenetics Implementation Consortium guidelines for cytochrome P450 2D6 genotype and codeine therapy: 2014 update. Clin Pharmacol Ther. 2014;95:376–82. - PMC - PubMed
1. Gaedigk A, Simon SD, Pearce RE, Bradford LD, Kennedy MJ, Leeder JS. The CYP2D6 activity score: translating genotype information into a qualitative measure of phenotype. Clin Pharmacol Ther. 2008;83:234–42. - PubMed
1. Crews KR, et al. Clinical Pharmacogenetics Implementation Consortium (CPIC) guidelines for codeine therapy in the context of cytochrome P450 2D6 (CYP2D6) genotype. Clin Pharmacol Ther. 2012;91:321–6. - PMC - PubMed
1. Hicks JK, et al. Clinical Pharmacogenetics Implementation Consortium (CPIC) Guideline for CYP2D6 and CYP2C19 Genotypes and Dosing of Selective Serotonin Reuptake Inhibitors. Clin Pharmacol Ther. 2015;98:127–34. - PMC - PubMed

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[1] PharmGKB. [Accessed September 16 2016];Gene Reference Materials for CYP2D6. < https://www.pharmgkb.org/page/cyp2d6RefMaterials>.

[2] PharmGKB. [Accessed September 16 2016];Gene Reference Materials for CYP2D6. < https://www.pharmgkb.org/page/cyp2d6RefMaterials>.

[3] Crews KR, et al. Clinical Pharmacogenetics Implementation Consortium guidelines for cytochrome P450 2D6 genotype and codeine therapy: 2014 update. Clin Pharmacol Ther. 2014;95:376–82. - PMC - PubMed

[4] Crews KR, et al. Clinical Pharmacogenetics Implementation Consortium guidelines for cytochrome P450 2D6 genotype and codeine therapy: 2014 update. Clin Pharmacol Ther. 2014;95:376–82. - PMC - PubMed

[5] Gaedigk A, Simon SD, Pearce RE, Bradford LD, Kennedy MJ, Leeder JS. The CYP2D6 activity score: translating genotype information into a qualitative measure of phenotype. Clin Pharmacol Ther. 2008;83:234–42. - PubMed

[6] Gaedigk A, Simon SD, Pearce RE, Bradford LD, Kennedy MJ, Leeder JS. The CYP2D6 activity score: translating genotype information into a qualitative measure of phenotype. Clin Pharmacol Ther. 2008;83:234–42. - PubMed

[7] Crews KR, et al. Clinical Pharmacogenetics Implementation Consortium (CPIC) guidelines for codeine therapy in the context of cytochrome P450 2D6 (CYP2D6) genotype. Clin Pharmacol Ther. 2012;91:321–6. - PMC - PubMed

[8] Crews KR, et al. Clinical Pharmacogenetics Implementation Consortium (CPIC) guidelines for codeine therapy in the context of cytochrome P450 2D6 (CYP2D6) genotype. Clin Pharmacol Ther. 2012;91:321–6. - PMC - PubMed

[9] Hicks JK, et al. Clinical Pharmacogenetics Implementation Consortium (CPIC) Guideline for CYP2D6 and CYP2C19 Genotypes and Dosing of Selective Serotonin Reuptake Inhibitors. Clin Pharmacol Ther. 2015;98:127–34. - PMC - PubMed

[10] Hicks JK, et al. Clinical Pharmacogenetics Implementation Consortium (CPIC) Guideline for CYP2D6 and CYP2C19 Genotypes and Dosing of Selective Serotonin Reuptake Inhibitors. Clin Pharmacol Ther. 2015;98:127–34. - PMC - PubMed

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

Affiliations

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

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Conflict of interest statement

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