CTCs in primary breast cancer (I).
ABSTRACT The prognostic and predictive value of circulating tumor cells (CTCs) in primary breast cancer patients is subject of several recent publications. In the context of neoadjuvant chemotherapy CTCs were detected in 22-23% of patients before and in 10-17% after systemic treatment. These findings did not correlate with primary tumor characteristics or tumor response rates. One major trial evaluated the prognostic value of CTCs in 2.026 primary breast cancer patients after tumor resection but before adjuvant chemotherapy. The prevalence of CTCs was 22%. In multivariate analysis, the presence of CTCs before treatment was shown to be an independent predictor for both disease-free (hazard ratio; HR 1.88) and overall survival (HR 1.91). Results demonstrate that not only the mere presence but also the quantity of CTCs is associated with worse outcome. The risk for recurrence or tumor-related death increased with higher numbers of CTCs detected (≥5 CTCs: HR 4.04 for DFS and 3.05 for OAS; p < 0.05). In subsequent analyses of smaller subgroups within this trial, using a cutoff for positivity of >1 CTC, 10% of patients with the detection of CTCs before chemotherapy remained CTC-positive after completion of chemotherapy. Eight percentage of initially negative patients showed CTCs immediately after chemotherapy. Early data demonstrate that persisting CTCs after cytostatic treatment correlate with a decreased disease-free survival (p = 0.0623). Increasing evidence confirms the prognostic relevance of CTCs in primary breast cancer. CTC detection could help to identify patients with increased risk for relapse. Present trials will show whether CTCs can also be used as a valid tool for treatment monitoring or direct treatment target.