# 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

## TL;DR

This review finds that BMI alone is not a reliable predictor of treatment outcomes for breast cancer patients taking CDK4/6 inhibitors, suggesting more detailed body composition analysis is needed.

## Contribution

The study systematically reviews the inconsistent role of BMI as a prognostic or predictive factor in HR+/HER2− breast cancer patients treated with CDK4/6 inhibitors.

## Key findings

- Four studies reported improved survival in higher BMI patients, but most found no significant BMI-outcome association.
- Computed tomography-based body composition metrics were more reliable than BMI for predicting prognosis.
- BMI alone is insufficient for predicting treatment response to CDK4/6 inhibitors in HR+/HER2− breast cancer.

## Abstract

This systematic review evaluated the association between BMI and clinical outcomes in patients with HR+/HER2− MBC receiving CDK4/6i. The 14 eligible studies yielded heterogenous results; while several investigations identified a prognostic advantage for overweight or obese patients, others failed to demonstrate a significant predictive correlation between BMI and survival outcomes. Current evidence indicates that BMI is an insufficient surrogate for body composition and does not consistently predict CDK4/6i efficacy. Further research integrating detailed anthropometric and metabolic profiling is needed to clarify the role of body composition in HR+/HER2− MBC.

Background/Objectives: 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. Methods: 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. Results: 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. Conclusions: 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.