Britt I Drögemöller1,2, Galen E B Wright1,3, Joanne Shih2, Jose G Monzon4, Karen A Gelmon5, Colin J D Ross2,3, Ursula Amstutz6, Bruce C Carleton7,8,9. 1. BC Children's Hospital Research Institute, Vancouver, BC, Canada. 2. Faculty of Pharmaceutical Sciences, University of British Columbia, Vancouver, BC, Canada. 3. Department of Medical Genetics, Faculty of Medicine, University of British Columbia, Vancouver, BC, Canada. 4. Tom Baker Cancer Centre, Calgary, AB, Canada. 5. BC Cancer Agency and University of British Columbia, Vancouver, BC, Canada. 6. University Institute of Clinical Chemistry, Inselspital Bern University Hospital, University of Bern, Bern, Switzerland. 7. BC Children's Hospital Research Institute, Vancouver, BC, Canada. bcarleton@popi.ubc.ca. 8. Division of Translational Therapeutics, Department of Pediatrics, Faculty of Medicine, University of British Columbia, Vancouver, BC, Canada. bcarleton@popi.ubc.ca. 9. Pharmaceutical Outcomes Programme, BC Children's Hospital Research Institute, 950 West 28th Ave, Vancouver, BC, V5Z 4H4, Canada. bcarleton@popi.ubc.ca.
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.
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 cancerpatients. Based on this information, it is recommended that alternatives to standard tamoxifen treatments may be considered in CYP2D6 poor or intermediate metabolizers.
Entities:
Keywords:
CYP2D6; Clinical practice guidelines; Pharmacogenomics; Systematic review; Tamoxifen
Authors: Thomas P Ahern; Lindsay J Collin; James W Baurley; Anders Kjærsgaard; Rebecca Nash; Maret L Maliniak; Per Damkier; Michael E Zwick; R Benjamin Isett; Peer M Christiansen; Bent Ejlertsen; Kristina L Lauridsen; Kristina B Christensen; Rebecca A Silliman; Henrik Toft Sørensen; Trine Tramm; Stephen Hamilton-Dutoit; Timothy L Lash; Deirdre Cronin-Fenton Journal: Cancer Epidemiol Biomarkers Prev Date: 2020-01-13 Impact factor: 4.254
Authors: David Twesigomwe; Galen E B Wright; Britt I Drögemöller; Jorge da Rocha; Zané Lombard; Scott Hazelhurst Journal: NPJ Genom Med Date: 2020-08-03 Impact factor: 8.617