Detection of circulating tumor cells: Prognostic and predictive role

Background: The effectiveness of CTC determination on progression free survival (PFS) and overall survival (OS) in early and advanced breast cancer as an adjunct to standard care of treatment was evaluated. Methods: Between November 2008 and March 2009, 22 metastatic and 12 early stage breast carcinoma patients, admitted to Ankara Oncology Training and Research Hospital and gave informed consent to participate, were included in this prospective trial. Patients' characteristics, treatment schedules and survival data were evaluated. Physical examination and routine radiological assessment were done regularly for the evaluation of response. CTC was detected by CellSearch method before and 9 to 12 weeks after the initiation of chemotherapy. Results: All patients were female. Median age was 48.0 (range: 29-65) and 52.5 (range: 35-66) in early stage and metastatic groups, respectively. CTC was positive (≥5) in 3 (13.6%) patients before chemotherapy and 6 (27.3%) patients at anytime during chemotherapy in the metastatic group whereas CTC was positive in only one patient in early stage group before and at anytime during chemotherapy. The median follow-up was 22.0 (range: 21-23) and 19.0 (range: 5-23) months in the early stage and metastatic groups, respectively. In the metastatic group, both median PFS and OS were significantly shorter in CTC positive patients compared to CTC negative patients (PFS: 4.0 vs 14.0 months, Log-Rank p=0.013; and OS: 8.0 months vs. 20.5 months, Log-Rank p<0.001). OS was affected from multiple visceral metastatic sites (p=0.055) and higher grade (p=0.044) besides CTC positivity (log rank p<0.001). Radiological response of chemotherapy during chemotherapy cycles was also correlated with better survival (p<0.001). Conclusions: As a result, CTC positivity was confirmed as a prospective marker even in a small patient population, in this single center study. Measurement of CTC by CellSearch method in metastatic breast carcinoma may be an indicative of early risk of relapse or death and even as less as two times of measurement during the whole chemotherapy program may be enough to have a decision but this finding should be confirmed with prospective trials in larger study populations.