Circulating tumor cells in metastatic breast cancer: Biologic staging beyond tumor burden

Background: The detection of circulating tumor cells (CTCs) predicts overall survival in patients with metastatic breast cancer (MBC). However, it is unknown whether CTCs have superior value compared with other standard prognostic factors. We compared the prognostic significance of CTCs with clinical and laboratory measures of tumor burden and phenotypic subtype of disease. Patients and Methods: One hundred fifty-one patients with MBC evaluated between 2000 and 2006 were included in this retrospective analysis. Circulating tumor cells were isolated and enumerated in whole blood using an immunomagnetic bead system (CellSearch™ System). Overall survival was evaluated according to the level of CTCs (negative: <5 CTCs per 7.5 mL of blood; positive: ≥ 5 CTCs per 7.5 mL of blood), Swenerton score, cancer antigen 27-29 level, age (<50 years vs. ≥ 50 years), hormone-receptor status and HER2 status, metastatic site, and type and line of therapy. Results: The median age of patients was 53 years (range, 24-88 years), and 44% of the patients had > 5 CTCs. The median overall survival for negative versus positive CTCs were 29.3 months and 13.5 months, respectively (P <0.0001). In the multivariable Cox model, the detection of ≥ 5 CTCs demonstrated the highest hazard ratio with 2.2 times the risk of death (P = 0.003). The prognostic value was independent of measure of tumor burden and type and line of therapy, and phenotypic subtype of the disease. Conclusion: Circulating tumor cells have superior and independent prognostic value of tumor burden and disease phenotype and might represent an important marker of tumor biology in MBC. Detection of CTCs should be considered for new staging stratification of patients with MBC.