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

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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.

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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.

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Author notes

  1. Britt I. Drögemöller and Galen E.B. Wright have contributed equally to this work.

Authors and Affiliations

  1. BC Children’s Hospital Research Institute, Vancouver, BC, Canada

    Britt I. Drögemöller, Galen E. B. Wright & Bruce C. Carleton

  2. Faculty of Pharmaceutical Sciences, University of British Columbia, Vancouver, BC, Canada

    Britt I. Drögemöller, Joanne Shih & Colin J. D. Ross

  3. Department of Medical Genetics, Faculty of Medicine, University of British Columbia, Vancouver, BC, Canada

    Galen E. B. Wright & Colin J. D. Ross

  4. Tom Baker Cancer Centre, Calgary, AB, Canada

    Jose G. Monzon

  5. BC Cancer Agency and University of British Columbia, Vancouver, BC, Canada

    Karen A. Gelmon

  6. University Institute of Clinical Chemistry, Inselspital Bern University Hospital, University of Bern, Bern, Switzerland

    Ursula Amstutz

  7. Division of Translational Therapeutics, Department of Pediatrics, Faculty of Medicine, University of British Columbia, Vancouver, BC, Canada

    Bruce C. Carleton

  8. Pharmaceutical Outcomes Programme, BC Children’s Hospital Research Institute, 950 West 28th Ave, Vancouver, BC, V5Z 4H4, Canada

    Bruce C. Carleton

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  1. Britt I. Drögemöller
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Consortia

the CPNDS Clinical Recommendations Group

  • Wan C. Chang
  • , Mary B. Connolly
  • , Francois Dionne
  • , Gabriella Groeneweg
  • , Catrina M. Loucks
  • , Stuart M. MacLeod
  • , Sheila Pritchard
  • , Shahrad R. Rassekh
  • , Shubhayan Sanatani
  • , Reo Tanoshima
  • , Sean A. Virani
  • , José G. Monzon
  • , Amit P. Bhavsar
  • , Michael J. Rieder
  • , Neil H. Shear
  • , Geoffrey Liu
  • , Philip Khayat
  • , Daniel Bernstein
  • , Lawrence J. Lesko
  •  & Folefac Aminkeng

Corresponding author

Correspondence to Bruce C. Carleton.

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The authors declare no conflict of interest.

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

Additional information

The members of the CPNDS Clinical Recommendations Group were listed in acknowlegements.

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Drögemöller, B.I., Wright, G.E.B., Shih, J. et al. CYP2D6 as a treatment decision aid for ER-positive non-metastatic breast cancer patients: a systematic review with accompanying clinical practice guidelines. Breast Cancer Res Treat 173, 521–532 (2019). https://doi.org/10.1007/s10549-018-5027-0

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  • DOI: https://doi.org/10.1007/s10549-018-5027-0

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