ABSTRACTThe prognostic value of the circulating tumor cells (CTCs), defined as EpCAM+, Cytokeratin (8, 18, 19)+ and CD45-nucleated cells, has been provided in metastatic breast cancer (mBC), with Level I of evidence. However, CTCs belong to a heterogeneous pool of rare cells, and there isn’t consensus on an univocal definition of CTCs. Here, we present a definition of metabolically altered CTCs (MBA-CTC) as CD45-negative cells with an increased extracellular acidification rate (iECAR), supported by the presence of iECAR among the hallmarks of cancer. We tested the prognostic value of MBA-CTC present in mBC patients before starting a new systemic therapy (T0) and 3-4 weeks after (T1). Samples were analyzed in parallel with CellSearch platform (CS). Standard RECIST criteria were used to determine patients’ responses to treatment.In our cohort of n=31 mBC patients, a level of MBA-CTCs above the cut-off was associated with: i) a shorter median PFS both pre-therapy (123 days vs 306; p<0.0001) and during therapy (139 vs 266 days; p= 0.0009); ii) a worse OS both pre-therapy (p=0.0003, 82% survival vs 20%) and during therapy (p=0.0301, 67% survival vs 38%); iii) good agreement with therapy response (kappa=0.685). Both the trend of MBA-CTCs over time and the combined results of the two assays (MBA and CS) enabled more accurate stratification. MBA and CS results showed fair (K=0.33) and poor (K=0.077) agreement at T0 and T1, respectively. This fact and the increased accuracy in combining results suggest that the assays detect different CTC subsets. In conclusion, MBA-CTCs does provide prognostic information at least equivalent to CS, and are even more informative when analyzed over time or combined with CS-CTCs.
Prognostic value of HER2-positive circulating tumor cells in patients with metastatic breast cancer
