Circulating tumor cells (CTCs) in metastatic breast cancer: Biological value beyond tumor burden.

Background: The detection of circulating tumor cells (CTCs) can predict progression-free (PFS) and overall survival (OS) in patients with metastatic breast cancer (MBC). We evaluated the prognostic significance of baseline CTCs in relation to standard measures of tumor burden. Furthermore, we assessed if the prognostic value of CTCs was related to any particular molecular phenotype. Patients and Methods: One hundred twenty-three consecutive MBC patients (pts) evaluated prospectively between 12/2000 and 5/2005 were included in this analysis. CTCs from 7.5 mL of whole blood were isolated and enumerated using CellSearch system. Prognostic value was determined by analyzing the following factors, baseline level of CTCs (negative: <5 CTCs/7.5 mL; positive: > 5 CTCs/7.5 mL), age (50 yrs/=50 yrs), hormonal receptor (HR), Her-2/neu status, metastatic site (visceral vs. non-visceral), Swenerton score, CA27.29 levels, and previous chemotherapy for MBC (none vs. pre-treated), Results: Median age was 52 years (range 24-88) and the median follow-up was 7.7 months (range 0-53.4 months). The median OS for the alive pts was 17.5 months. Fifty-two pts (42%) had positive CTCs and abnormal CA27.29 was detected in 80 pts (66%). The median OS for patients with negative vs. positive CTCs were 28.3 months (range 1.28 - 31.24) and 12.8 months (range 1.71 to 36.83) respectively (p=0.0001). In the multivariable model, HR status, CTCs, and CA27.29 level were the only factors significantly related to OS. CTCs demonstrated the strongest predictor for OS and were associated with 2.53 times the risk of death (p = 0.003). The prognostic value of CTCs was independent of line of treatment, site of recurrence and phenotype of the disease. Conclusions: CTCs demonstrated prognostic value independent of standard measures of tumor burden and phenotypic characteristics of the disease. CTCs are an important marker of tumor biology in metastatic breast cancer.