Prognostic Value of Metabolic–Muscle Reserve Index in HR+/HER2− Metastatic Breast Cancer Treated with CDK4/6 Inhibitors

Background/Objectives: Despite the established benefits of cyclin-dependent kinase 4/6 (CDK4/6) inhibitors, survival outcomes remain heterogeneous among patients with hormone receptor-positive (HR+)/human epidermal growth factor receptor 2-negative (HER2−) metastatic breast cancer. We developed the Metabolic–Muscle Reserve Index (MMRI), integrating tumor metabolic activity, biochemical status, and skeletal muscle quantity, and investigated its relationship with progression-free survival (PFS) and overall survival (OS). Methods: We conducted a retrospective study involving 168 patients with HR+/HER2− metastatic breast cancer who were treated with CDK4/6 inhibitors. MMRI incorporated baseline PET/CT-derived maximum standardized uptake value (SUVmax), serum lactate dehydrogenase (LDH), albumin, and CT-derived psoas volume index (PVI). Receiver operating characteristic (ROC) analysis identified an exploratory MMRI cut-off. We examined survival using Kaplan–Meier analysis and Cox regression. Results: ROC analysis identified an MMRI cut-off of 10.68 for mortality discrimination, with an AUC of 0.642 (95% CI: 0.563–0.716). Patients with MMRI > 10.68 had shorter median PFS (14.1 vs. 28.1 months; p < 0.001) and OS (29.7 months vs. not reached; p < 0.001) than those with MMRI ≤ 10.68. In multivariable Cox analysis, higher MMRI was associated with shorter PFS (HR: 1.857, 95% CI: 1.329–2.596; p = 0.0003) and OS (HR: 1.974, 95% CI: 1.368–2.846; p = 0.0003). Conclusions: Patients with higher MMRI values experienced shorter PFS and OS during CDK4/6 inhibitor treatment for HR+/HER2− metastatic breast cancer. Given its modest discriminative performance, these findings remain exploratory and require prospective external validation before clinical application.