Abstract
PURPOSE: Circulating tumor cells (CTCs) are strongly prognostic for overall survival (OS) in metastatic breast cancer although additional prognostic biomarkers are needed. We evaluated the complementary prognostic value of tumor-derived extracellular vesicles (tdEVs) next to CTCs. METHODS: We applied the open-source ACCEPT software to archived CellSearch images from the prospective clinical trial SWOG0500 to enumerate CTCs and tumor-derived extracellular vesicles (tdEVs) before and after one cycle of chemotherapy. RESULTS: CTCs enumerated by ACCEPT were strongly correlated with classical ocular enumeration (correlation r = 0.98). OS was worse with elevated tdEVs (median OS for high/medium/low groups: 17.1 v 29.0 v 43.3 months; P < .0001). In patients with longer OS by CTC counts (< 5 CTC/7.5 mL blood), elevated tdEV levels were independently associated with poorer OS (multivariable analysis P < .001). OS was also longer for patients with low tdEVs after one cycle of chemotherapy (median OS for high/medium/low group: 10.8 v 17.8 v 26.7; P < .0001). CONCLUSION: This study highlights the complementary prognostic significance of tdEVs in metastatic breast cancer before and after one cycle of chemotherapy.