Positron-emission tomography as a predictor of response to first-line cyclin-dependent kinase 4/6 inhibitors in patients with metastatic ER-positive HER2-negative breast cancer.

Cyclin-dependent kinase 4/6 inhibitors (CDK4/6i) are the standard first-line treatment for metastatic estrogen receptor-positive, HER2-negative breast cancer, yet acquired resistance remains a major challenge. Reliable biomarkers for prognostic stratification are therefore needed. We retrospectively analyzed 174 patients treated with first-line CDK4/6i between 2018 and 2023 who underwent baseline 18F-fluorodeoxyglucose positron emission tomography. Associations between baseline SUVmax and clinical outcomes were assessed using Kaplan-Meier estimates, Cox proportional hazards models, logistic regression for early progression, and receiver-operating characteristic (ROC) analysis for cut-off determination. Higher SUVmax was significantly associated with shorter progression-free survival (PFS; HR 1.11, 95% CI 1.05-1.16, p < 0.001) and overall survival (OS; HR 1.10, 95% CI 1.02-1.18, p = 0.016). Patients with SUVmax <8.0 experienced markedly longer PFS and improved 2-year PFS compared with those with SUVmax ≥8.0. Similarly, 2-year OS was substantially higher among patients with lower SUVmax values. In multivariable analysis, SUVmax remained an independent prognostic factor for PFS. Higher SUVmax was also associated with early progression, with an 18% increase in odds per unit (OR 1.18, 95% CI 1.05-1.33). These findings demonstrate that baseline SUVmax is a strong and readily accessible prognostic biomarker in patients receiving CDK4/6i, helping to identify individuals at elevated risk of early disease progression. Prospective validation is warranted.