The impact of sarcopenia on adverse effects and survival in patients with metastatic hormone receptor-positive breast cancer treated with CDK4/6 inhibitors

Abstract

Breast cancer is the most commonly diagnosed malignancy worldwide. In hormone receptor-positive, human epidermal growth factor receptor 2-negative metastatic breast cancer (mBC), cyclin-dependent kinase 4/6 inhibitors (CDK4/6i) are the standard treatment. Sarcopenia, characterized by progressive muscle loss, is increasingly recognized as a factor influencing cancer outcomes. This study evaluated the impact of preexisting sarcopenia on overall survival, progression-free survival, and treatment-related adverse effects in patients receiving CDK4/6i therapy. A retrospective analysis was conducted on hormone receptor-positive mBC patients treated with CDK4/6i at Istanbul Training and Research Hospital between 2020 and 2024. Patients were classified as sarcopenic or non-sarcopenic based on pretreatment computed tomography muscle mass measurements. Survival outcomes were assessed using Kaplan-Meier analysis, and treatment-related adverse effects, including dose reductions, acute kidney injury, liver function test abnormalities, and neutropenia, were compared between groups. Among 111 patients, 20 (18%) were identified as sarcopenic. Sarcopenia was associated with significantly lower overall survival and progression-free survival compared to non-sarcopenic patients (P=.000). However, no significant differences were observed between groups in treatment-related adverse effects, including the need for dose reduction, acute kidney injury, liver function abnormalities, and neutropenia (P>.05). Sarcopenia negatively impacts survival outcomes in hormone receptor-positive mBC patients receiving CDK4/6i therapy. Routine screening and targeted interventions, such as nutritional support and physical activity programs, may help improve patient resilience and treatment efficacy. Further research is needed to develop strategies to mitigate sarcopenia's impact on survival in this patient population. © 2025 Elsevier B.V., All rights reserved.