Optimizing tamoxifen therapy in breast cancer: a narrative review of dose escalation in patients with CYP2D6 polymorphisms

INTRODUCTION: The efficacy of tamoxifen in breast cancer endocrine therapy may be compromised by factors such as low adherence, drug interactions, and polymorphisms in CYP2D6, which is essential for converting tamoxifen into its active metabolite, endoxifen. Despite the recognized inter-individual variability, dose adjustment strategies based on CYP2D6 status or endoxifen levels have not yet been established as standard clinical practice. AREAS COVERED: This narrative review examines evidence on optimizing TAM therapy through dose escalation in patients with altered CYP2D6 function. We explore the impact of tamoxifen dose escalation on endoxifen concentrations, safety, and clinical efficacy in patients with altered CYP2D6 enzyme function. A literature search in PubMed and LILACS yielded articles published between 2015 and 2025, utilizing descriptors for tamoxifen, breast cancer, CYP2D6, and dose escalation/adjustment. RESULTS: Tamoxifen dose escalation strategies show promise in optimizing endoxifen concentrations for patients with impaired CYP2D6 metabolism, without significant short-term adverse effects. However, the lack of data on long-term toxicity and clinical efficacy raises concerns about the sustainability of this approach. For dose escalation to become standard practice, further research is essential to understand the long-term implications of higher tamoxifen doses on patient outcomes. its integration into clinical protocols requires comprehensive evidence clarifying long-term effects.