Cyclin-dependent kinase 4/6 inhibitors (CDK4/6i) have improved progression-free survival (PFS), overall survival (OS), and quality of life in advanced breast cancer. Although [¹⁸F]FDG-PET/CT is an established imaging option in selected patients with metastatic breast cancer, its optimal use for treatment response assessment, particularly during CDK4/6i therapy, remains to be clarified. This study evaluated the prognostic value of metabolic response measured by [¹⁸F]FDG-PET/CT in patients treated with CDK4/6i.

The study included ninety-seven patients (median age 61; interquartile range [IQR] 53–72 years) with advanced hormone receptor-positive/human epidermal growth factor receptor 2-negative (HR+/HER2-negative) breast cancer treated with CDK4/6i, who underwent [¹⁸F]FDG-PET/CT at baseline and for response assessment. The majority (72%) were treated in the first-line setting. Maximum standardized uptake value (SUV_max) at the first response assessment (SUV_as) and percentage of SUV_max change from baseline to first response assessment (ΔSUV_max) were evaluated as prognostic factors for PFS and OS.

With a median follow-up of 27.5 months, median PFS was 33.1 months, with a 2-year PFS of 65.6% [95% confidence interval [CI]: 54.8–75.4%]. Eight OS events occurred; the 3-year OS was 91.7% [95% CI 80.6–96.6%], and median OS was not reached. The median ΔSUV_max reduction was 57% (IQR 33–73%). A greater ΔSUV_max reduction was associated with longer PFS in multivariable analysis (p = 0.003). Associations with OS were also observed but should be considered exploratory because of the limited number of events.

These findings suggest [¹⁸F]FDG-PET/CT metabolic response as a potential prognostic tool in advanced HR+/HER2-negative breast cancer treated with CDK4/6i, though larger studies are needed for confirmation.