Can CCR2+ non-classical monocytes serve as a diagnostic biomarker in HER2-negative breast cancer? A pilot study

HER2-negative breast cancers, particularly triple-negative (TNBC) and luminal B (LB) variants, require novel biomarkers for rapid diagnostic confirmation due to their aggressive nature and radiological challenges. This pilot study evaluated whether subset-specific CCR2 expression on peripheral monocytes could serve as a high-fidelity liquid biopsy biomarker. We analyzed monocyte subsets-classical (CD14++CD16-), intermediate (CD14++CD16+), and non-classical (CD14 + CD16++)-via flow cytometry in 60 HER2-negative breast cancer patients and 30 healthy controls. Results identified a significant systemic remodeling of the monocyte lineage. A dramatic, nearly four-fold increase in CCR2 expression was observed within the non-classical subset (18.32% vs. 4.29% in controls; p < 0.001). ROC analysis demonstrated that the percentage of CCR2+ non-classical monocytes distinguished cancer patients with 96% sensitivity and 96% specificity. Notably, this immunophenotypic shift was independent of tumor stage, grade, and systemic inflammatory markers. These findings suggest that 'inducible' non-classical monocytes could serve as a specific hallmark of early-stage HER2-negative breast cancer, potentially providing a minimally invasive tool for early diagnosis.