Longitudinal assessment of circulating tumor cells (CTCs) in the peripheral blood of patients with metastatic breast cancer (MBC) on treatment with CDK4/6 inhibitors.

Abstract

e13064 Background: The detection and enumeration of circulating tumor cells (CTCs) in the peripheral blood is an independent poor prognostic factor for patients (pts) with metastatic breast cancer (MBC), while longitudinal CTC assessment holds promising role also as a real-time biomarker for monitoring treatment efficacy and disease progression. CDK4/6 inhibitors represent a key treatment option for hormone receptor-positive (HR+) MBC. We herein aimed to assess the clinical value of CTCs and their kinetics for HR+ MBC pts treated with CDK4/6 inhibitors. Methods: Peripheral blood (PB) was obtained from pts with HR+ MBC: a) at baseline before the start of CDK4/6 inhibitors plus endocrine treatment (N = 39), and b) at the first evaluation of treatment response (N = 24/39 pts; paired samples). CTCs were in parallel isolated using Ficoll density gradient centrifugation, and the automated size-based Parsortix system (ANGLE plc). CTC detection and enumeration was performed by immunofluorescence staining for cytokeratins (CKs)/CD45/dapi and observation via fluorescence microscopy. Results: CTCs (CK+/CD45- cells) were detected by any assay in 15/39 (38.5%) of pts at baseline and in 5/24 (20.8%) at the first evaluation, with a total of 71 and 25 CTCs identified, respectively (mean CTC No per patient: n = 1.82 and 1.04). Overall 12 pts (50%) were CTC-positive at any time point, whereas 12 pts (50%) were consistently CTC-negative at both time points. A significant overall reduction in CTCs counts was observed from baseline to first evaluation (Sum of Ranks: 65 vs 13, p = 0.038, Wilcoxon t test). No associations were found between CTC detection or their kinetics, with clinicopathological features or treatment response. However, Kaplan Meier analysis revealed significantly reduced overall survival (OS) rates among pts with ≥ 5 CTCs at baseline (median OS: 18.0 versus 48.4 months; p = 0.010), at first evaluation (median OS: 18.0 versus 47.2 months; p = 0.000), or at any time point (median OS: 18.0 versus 47.2 months; p = 0.013). Conclusions: CTCs numbers significantly decreased during treatment in HR+ MBC pts receiving CDK4/6 inhibitors. The presence of ≥5 CTCs at any time point was strongly associated with significantly reduced overall survival, supporting their role as a negative prognostic biomarker in HR+ MBC.