Pharmacogenomics Implication of Tamoxifen in Breast Cancer Treatment: Clinical Relevance and Future Directions

Tamoxifen is a cornerstone therapy for estrogen receptor-positive (ER+) breast cancer, improving survival and reducing recurrence. Its efficacy and toxicity, however, vary due to genetic polymorphisms influencing metabolism and transport. Key genes, such as CYP2D6, CYP3A4, and ATP-binding cassette transporters (ABCB1, ABCC2), are crucial in forming and distributing active metabolites like endoxifen. This review explores tamoxifen pharmacogenetics through an analysis of literature from PubMed, Scopus, Google Scholar, and PharmaGKB. Genetic variations like CYP2D6*10 in Asians and CYP2D6*17/29 in Africans impact therapeutic outcomes. Barriers to personalized tamoxifen therapy include inconsistent guidelines, limited access to genetic testing, and underrepresentation of ethnic groups in research.The findings highlight the need for multidisciplinary approaches integrating genetic, clinical, and environmental factors to optimize therapy. Large-scale, diverse, population-specific studies are essential to establish universal pharmacogenetic guidelines.