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.

PubMed Disclaimer

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

Cited by

Characterization of Novel CYP2D6 Alleles across Sub-Saharan African Populations.
Wang WY, Twesigomwe D, Nofziger C, Turner AJ, Helmecke LS, Broeckel U, Derezinski AD, Hazelhurst S, Gaedigk A. Wang WY, et al. J Pers Med. 2022 Sep 24;12(10):1575. doi: 10.3390/jpm12101575. J Pers Med. 2022. PMID: 36294714 Free PMC article.
CYP2D6 Genotype Predicts Plasma Concentrations of Tamoxifen Metabolites in Ethiopian Breast Cancer Patients.
Ahmed JH, Makonnen E, Fotoohi A, Aseffa A, Howe R, Aklillu E. Ahmed JH, et al. Cancers (Basel). 2019 Sep 12;11(9):1353. doi: 10.3390/cancers11091353. Cancers (Basel). 2019. PMID: 31547390 Free PMC article.
Frequencies of CYP2D6 genetic polymorphisms in Arab populations.
Alali M, Ismail Al-Khalil W, Rijjal S, Al-Salhi L, Saifo M, Youssef LA. Alali M, et al. Hum Genomics. 2022 Feb 5;16(1):6. doi: 10.1186/s40246-022-00378-z. Hum Genomics. 2022. PMID: 35123571 Free PMC article. Review.
Factors Influencing Pharmacokinetics of Tamoxifen in Breast Cancer Patients: A Systematic Review of Population Pharmacokinetic Models.
Dilli Batcha JS, Raju AP, Matcha S, Raj S EA, Udupa KS, Gota V, Mallayasamy S. Dilli Batcha JS, et al. Biology (Basel). 2022 Dec 28;12(1):51. doi: 10.3390/biology12010051. Biology (Basel). 2022. PMID: 36671744 Free PMC article. Review.
Pharmacogenomic Testing: Clinical Evidence and Implementation Challenges.
Hippman C, Nislow C. Hippman C, et al. J Pers Med. 2019 Aug 7;9(3):40. doi: 10.3390/jpm9030040. J Pers Med. 2019. PMID: 31394823 Free PMC article. Review.

See all "Cited by" articles

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

Publication types

Actions
Actions
Actions

MeSH terms

Actions
Actions
Actions
Actions
Actions
Actions
Actions
Actions
Actions
Actions
Actions
Actions
Actions

Substances

Actions
Actions
Actions
Actions
Actions

Grants and funding

LinkOut - more resources

Full Text Sources
Other Literature Sources
- scite Smart Citations
Medical
- MedlinePlus Health Information

Save citation to file

Email citation

Add to Collections

Add to My Bibliography

Your saved search

Create a file for external citation management software

Your RSS Feed

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

Affiliations

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

Authors

Affiliations

Abstract

Conflict of interest statement

Figures

Similar articles

Cited by

References

Publication types

MeSH terms

Substances

Grants and funding

LinkOut - more resources

Full Text Sources

Other Literature Sources

Medical

Abstract

Conflict of interest statement

Figures

Similar articles

Cited by

References

Publication types

MeSH terms

Substances

Related information

Grants and funding

LinkOut - more resources

Full Text Sources

Other Literature Sources

Medical