Influence of CYP2D6 gene variants on the response to tamoxifen in oncologic patients.
DOI:
https://doi.org/10.69849/wszcwa29Keywords:
CYP2D6, Tamoxifen, Pharmacogenomics, Breast cancer, Therapeutic responseAbstract
Tamoxifen is the standard therapy for hormone receptor-positive (ER+) breast cancer; however, its efficacy depends on hepatic bioactivation by the CYP2D6 enzyme into its active metabolite, endoxifen. This study investigated the influence of CYP2D6 gene variants on the therapeutic response to tamoxifen. An integrative literature review was conducted, guided by the PRISMA protocol, searching PubMed, Scopus, Web of Science, and SciELO databases (2005-2023). The results demonstrate that poor (PM) and intermediate (IM) metabolizers have reduced endoxifen levels, resulting in significantly higher tumor recurrence rates (up to 29%) compared to normal metabolizers (14.9%). It was observed that protection against contralateral breast cancer is compromised in low enzymatic activity profiles, while ultrarapid metabolizers face a higher risk of discontinuation due to toxicity. The conclusion highlights that prior CYP2D6 genotyping and monitoring of drug interactions (such as the use of inhibitory antidepressants) are fundamental for precision medicine. Dose adjustment or therapy substitution in deficient profiles is essential to optimize survival and reduce therapeutic failures, reinforcing the pharmacist's role in personalizing oncological therapy.
References
BOUCENNA, Amira et al. Influence of CYP2D6, CYP2C19 and CYP3A5 polymorphisms on plasma levels of tamoxifen metabolites in Algerian women with ER+ breast cancer. Egyptian Journal of Medical Human Genetics, [S. l.], v. 23, n. 1, 2022. DOI: https://doi.org/10.1186/s43042-022-00332-7.
BROOKS, Jennifer D. et al. CYP2D6 phenotype, tamoxifen, and risk of contralateral breast cancer in the WECARE Study. Breast Cancer Research, [S. l.], v. 20, n. 1, 2018. DOI: https://doi.org/10.1186/s13058-018-1083-y.
DECENSI, Andrea et al. Association of CYP2D6 genotype and tamoxifen metabolites with breast cancer recurrence in a low-dose trial. npj Breast Cancer, [S. l.], v. 7, n. 1, 2021. DOI: https://doi.org/10.1038/s41523-021-00236-6. Acesso em: 15 set. 2025.
GOETZ, Matthew P. et al. Pharmacogenetics of tamoxifen biotransformation is associated with clinical outcomes of efficacy and hot flashes. Journal of Clinical Oncology: Official Journal of the American Society of Clinical Oncology, [S. l.], v. 23, n. 36, p. 9312–9318, 2005. DOI: https://doi.org/10.1200/JCO.2005.03.3266. Disponível em: https://pubmed.ncbi.nlm.nih.gov/16361630/. Acesso em: 14 set. 2025.
HE, Wei et al. CYP2D6 Genotype Predicts Tamoxifen Discontinuation and Prognosis in Patients With Breast Cancer. Journal of Clinical Oncology, [S. l.], v. 38, n. 6, p. 548–557, 2020. DOI: https://doi.org/10.1200/jco.19.01535.
HERTZ, Daniel L.; MCLEOD, Howard L.; IRVIN, William J. Tamoxifen and CYP2D6: A Contradiction of Data. The Oncologist, [S. l.], v. 17, n. 5, p. 620–630, 2012. DOI: https://doi.org/10.1634/theoncologist.2011-0418. Acesso em: 8 set. 2025.
KHALAJ, Zahra et al. Clinical Trial: CYP2D6 Related Dose Escalation of Tamoxifen in Breast Cancer Patients With Iranian Ethnic Background Resulted in Increased Concentrations of Tamoxifen and Its Metabolites. Frontiers in Pharmacology, [S. l.], v. 10, 2019. DOI: https://doi.org/10.3389/fphar.2019.00530.
LAMMERS, L. A. et al. The impact of CYP2D6-predicted phenotype on tamoxifen treatment outcome in patients with metastatic breast cancer. British Journal of Cancer, [S. l.], v. 103, n. 6, p. 765–771, 2010. DOI: https://doi.org/10.1038/sj.bjc.6605800. Acesso em: 15 set. 2025.
PROVINCE, M. A. et al. CYP2D6 Genotype and Adjuvant Tamoxifen: Meta-Analysis of Heterogeneous Study Populations. Clinical Pharmacology & Therapeutics, [S. l.], v. 95, n. 2, p. 216–227, 2013. DOI: https://doi.org/10.1038/clpt.2013.186.
SCHROTH, Werner. Association Between CYP2D6 Polymorphisms and Outcomes Among Women With Early Stage Breast Cancer Treated With Tamoxifen. JAMA, [S. l.], v. 302, n. 13, p. 1429, 2009. DOI: https://doi.org/10.1001/jama.2009.1420.
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Copyright (c) 2026 Maria Eduarda Toledo Dias, Danielly Beraldo dos Santos Silva (Autor)
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