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

• Published in: Breast cancer research and treatment Vol. 173; no. 3; pp. 521 - 532
• Main Authors: Drögemöller, Britt I., Wright, Galen E. B., Shih, Joanne, Monzon, Jose G., Gelmon, Karen A., Ross, Colin J. D., Amstutz, Ursula, Carleton, Bruce C.
• Format: Journal Article
• Language: English
• Published: New York Springer US 01.02.2019; Springer; Springer Nature B.V
• Subjects: Alleles; Antineoplastic Agents, Hormonal - pharmacology; Antineoplastic Agents, Hormonal - therapeutic use; Biomarkers, Tumor; Breast cancer; Breast Neoplasms - diagnosis; Breast Neoplasms - genetics; Breast Neoplasms - therapy; Cancer metastasis; Cancer patients; Cancer research; Cancer therapies; Care and treatment; Clinical Decision-Making; Clinical practice guidelines; Confounding Factors (Epidemiology); CYP2D6 protein; Cytochrome P-450; Cytochrome P-450 CYP2D6 - genetics; Cytochrome P-450 CYP2D6 Inhibitors - pharmacology; Cytochrome P-450 CYP2D6 Inhibitors - therapeutic use; Cytochrome P450; Disease Management; Estrogen receptors; Estrogens; Evidence-based medicine; Female; Genetic diversity; Genetic research; Genetic screening; Genetic testing; Genetic Variation; Genotype; Genotyping; Humans; Literature reviews; Medicine; Medicine & Public Health; Metastases; Metastasis; Oncology; Patients; Pharmacogenetics; Phenols (Class of compounds); Phenotypes; Practice guidelines (Medicine); Practice Guidelines as Topic; Prognosis; Receptors, Estrogen - genetics; Receptors, Estrogen - metabolism; Review; Survival; Tamoxifen; Tamoxifen - pharmacology; Tamoxifen - therapeutic use; Clinical practice guidelines; Systematic review; Tamoxifen; CYP2D6; Pharmacogenomics
• ISSN: 0167-6806; 1573-7217
• DOI: 10.1007/s10549-018-5027-0

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.