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Breast Cancer Research and Treatment

, Volume 173, Issue 3, pp 521–532 | Cite as

CYP2D6 as a treatment decision aid for ER-positive non-metastatic breast cancer patients: a systematic review with accompanying clinical practice guidelines

  • Britt I. Drögemöller
  • Galen E. B. Wright
  • Joanne Shih
  • Jose G. Monzon
  • Karen A. Gelmon
  • Colin J. D. Ross
  • Ursula Amstutz
  • Bruce C. CarletonEmail author
  • the CPNDS Clinical Recommendations Group
Review

Abstract

Purpose

Tamoxifen is one of the principal treatments for estrogen receptor (ER)-positive breast cancer. Unfortunately, between 30 and 50% of patients receiving this hormonal therapy relapse. Since CYP2D6 genetic variants have been reported to play an important role in survival outcomes after treatment with tamoxifen, this study sought to summarize and critically appraise the available scientific evidence on this topic.

Methods

A systematic literature review was conducted to identify studies investigating associations between CYP2D6 genetic variation and survival outcomes after tamoxifen treatment. Critical appraisal of the retrieved scientific evidence was performed, and recommendations were developed for CYP2D6 genetic testing in the context of tamoxifen therapy.

Results

Although conflicting literature exists, the majority of the current evidence points toward CYP2D6 genetic variation affecting survival outcomes after tamoxifen treatment. Of note, review of the CYP2D6 genotyping assays used in each of the studies revealed the importance of comprehensive genotyping strategies to accurately predict CYP2D6 metabolizer phenotypes.

Conclusions and recommendations

Critical appraisal of the literature provided evidence for the value of comprehensive CYP2D6 genotyping panels in guiding treatment decisions for non-metastatic ER-positive breast cancer patients. Based on this information, it is recommended that alternatives to standard tamoxifen treatments may be considered in CYP2D6 poor or intermediate metabolizers.

Keywords

Clinical practice guidelines CYP2D6 Pharmacogenomics Systematic review Tamoxifen 

Notes

Acknowledgements

The members of the Canadian Pharmacogenomics Network for Drug Safety Clinical Recommendations Group are: Vancouver, BC, Canada—University of British Columbia: Ursula Amstutz, Bruce C. Carleton, Wan C. Chang, Mary B. Connolly, Francois Dionne, Britt I. Drögemöller, Karen A. Gelmon, Gabriella Groeneweg, Catrina M. Loucks, Stuart M. MacLeod, Sheila Pritchard (Sheilapritchard@me.com), Shahrad R. Rassekh, Colin J.D. Ross, Shubhayan Sanatani, Joanne Shih, Reo Tanoshima, Sean A. Virani, Galen E.B. Wright. Calgary AB, Canada—University of Calgary: José G. Monzon. Edmonton AB, Canada—University of Alberta: Amit P. Bhavsar. London, ON, Canada—University of Western Ontario and London Health Sciences Centre: Michael J. Rieder. Toronto, ON, Canada—Sunnybrook Health Sciences Centre: Neil H. Shear; University of Toronto and Hospital for Sick Children: Shinya Ito, Ontario Cancer Institute: Geoffrey Liu. Montréal, QC, Canada—Philip Khayat. Stanford, CA, USA—Stanford University: Daniel Bernstein. Orlando, FL, USA—University of Florida: Lawrence J. Lesko. Singapore—Agency for Science, Technology and Research—Folefac Aminkeng.

Funding

This study was funded by Canadian Institutes of Health (CIHR) Research Meetings, Planning, and Dissemination Grant–Knowledge Translation Supplement (FRN 114403). BID received stipends from the CIHR, CIHR-DSECT and the Michael Smith Foundation for Health Research. GEBW received stipends from the CIHR and CIHR-DSECT.

Compliance with ethical standards

Conflict of interest

The authors declare no conflict of interest.

Ethical approval

This article does not contain any studies with human participants or animals performed by any of the authors.

Supplementary material

10549_2018_5027_MOESM1_ESM.doc (173 kb)
Supplementary material 1 (DOC 173 KB)
10549_2018_5027_MOESM2_ESM.xlsx (31 kb)
Supplementary material 2 (XLSX 30 KB)

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Copyright information

© Springer Science+Business Media, LLC, part of Springer Nature 2018

Authors and Affiliations

  • Britt I. Drögemöller
    • 1
    • 2
  • Galen E. B. Wright
    • 1
    • 3
  • Joanne Shih
    • 2
  • Jose G. Monzon
    • 4
  • Karen A. Gelmon
    • 5
  • Colin J. D. Ross
    • 2
    • 3
  • Ursula Amstutz
    • 6
  • Bruce C. Carleton
    • 1
    • 7
    • 8
    Email author
  • the CPNDS Clinical Recommendations Group
  1. 1.BC Children’s Hospital Research InstituteVancouverCanada
  2. 2.Faculty of Pharmaceutical SciencesUniversity of British ColumbiaVancouverCanada
  3. 3.Department of Medical Genetics, Faculty of MedicineUniversity of British ColumbiaVancouverCanada
  4. 4.Tom Baker Cancer CentreCalgaryCanada
  5. 5.BC Cancer Agency and University of British ColumbiaVancouverCanada
  6. 6.University Institute of Clinical Chemistry, Inselspital Bern University HospitalUniversity of BernBernSwitzerland
  7. 7.Division of Translational Therapeutics, Department of Pediatrics, Faculty of MedicineUniversity of British ColumbiaVancouverCanada
  8. 8.Pharmaceutical Outcomes ProgrammeBC Children’s Hospital Research InstituteVancouverCanada

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