High independent prognostic and predictive value of circulating tumor cells compared with serum tumor markers in a large prospective trial in first-line chemotherapy for metastatic breast cancer patients

Circulating tumor cells (CTCs) are a prognostic marker in metastatic breast cancer, but comparisons with serum tumor markers (CA 15-3, carcinoembryonic antigen and lactate dehydrogenase) variations are needed. CTCs were counted with CellSearch® at baseline, before cycle 2 (C2) and cycle 3 or 4 (C3/4) in 267 metastatic breast cancer patients on first-line chemotherapy with/without targeted therapy. Baseline CTC detection rate was 65% with ≥1 CTC/7.5 ml threshold and 44% with ≥5 CTC/7.5 ml and was independent of subtypes (luminal, triple negative, human epithelial growth factor receptor 2 (HER2)+). CTCs were associated with tumor markers, bone/liver involvement, tumor burden and performance status. CTC detection ≥1 CTC/7.5 ml was a strong prognostic factor for progression-free survival (PFS), P < 0.0001. Threshold of CTC ≥5 was statistically significant for PFS and overall survival (OS), P = 0.03 on multivariate analysis. Among patients with ≥5 CTC/7.5 ml at baseline, 50% had