The Prognostic and Predictive Value of Body Mass Index in Patients with HR+/HER2− Breast Cancer Treated with CDK4/6 Inhibitors: A Systematic Literature Review

<b>Background/Objectives</b>: Cyclin-dependent kinase 4/6 inhibitors combined with endocrine therapy have become the standard of care for HR+/HER2- metastatic breast cancer. Given the metabolic functions of CDK4/6 and the endocrine activity of adipose tissue, body mass index has been proposed as a potential prognostic or predictive factor in this setting. This systematic review aimed to summarize current evidence on the association between BMI and treatment outcomes in HR+/HER2- MBC patients receiving CDK4/6i. <b>Methods</b>: A systematic literature search was conducted in PubMed and Scopus databases, covering publications from 2015 to 2025. We included real-world studies and clinical cohorts reporting survival outcomes of HR+/HER2- MBC patients treated with CDK4/6i in relation to BMI and other body composition parameters. <b>Results</b>: From 69 records identified, 14 studies met the inclusion criteria. Findings were heterogenous; four studies reported improved survival outcomes in higher BMI patients, whereas most identified no significant association. Studies incorporating computed tomography-based metrics demonstrated that body composition parameters such as visceral adiposity and skeletal muscle area were more reliable predictors of prognosis than BMI alone. <b>Conclusions</b>: Our findings indicate that BMI as a standalone metric is an insufficient predictor of clinical outcomes or treatment response for those receiving CDK4/6i, highlighting the need for precise body composition evaluation. More detailed anthropometric and metabolic profiling could clarify the clinical significance of adiposity in HR+/HER2- MBC.