Circulating tumor cells in metastatic breast cancer: from prognostic stratification to modification of the staging system?

Background: The aim of the current study was to assess the prognostic value of baseline circulating tumor cells (CTCs) in a large cohort of patients with newly diagnosed metastatic breast cancer (MBC).

Methods: This retrospective study included 185 patients with newly diagnosed MBC evaluated between 2001 and 2007. CTCs were isolated and enumerated before patients started first-line treatment using the CellSearch system. Overall survival (OS) was calculated from the date of CTC measurement, estimated by the Kaplan-Meier product limit method, and compared between groups with the log-rank test. Cox proportional hazards models were fitted to determine the association between CTC levels and OS after controlling for other prognostic factors.

Results: The median age of the patients at the time of MBC diagnosis was 49 years. Fifty-six (30.3%) patients presented with de novo metastatic disease, and 129 (69.7%) presented with newly recurrent breast cancer. A total of 114 patients (61.6%) had CTC<5, and 71 (38.4%) had CTC >or= 5. The median OS was 28.3 months and 15 months (P< .0001) for patients with CTC<5 and CTC >or= 5, respectively. Superior survival among patients with CTC<5 was observed regardless of hormone receptor and HER-2/neu status, site of first metastases, or whether the patient had recurrent or de novo metastatic disease. In the multivariate model, patients with CTC >or= 5 had a hazards ratio of death of 3.64 (95% confidence interval, 2.11-6.30) compared with patients with CTC <5.

Conclusions: The results of this large retrospective study confirms that CTCs are a strong independent predictor of survival among women with either de novo or newly recurrent MBC. CTCs should be considered as a new stratification method for women with newly diagnosed MBC.