Evaluation of circulating tumor cells in patients with breast cancer: multi-institutional clinical trial in Japan

BACKGROUND: With the development of the CellSearch System, it has become possible to measure circulating tumor cell (CTC) levels with high reproducibility, and the CTC test is currently being used clinically for patients with metastatic breast cancer in the United States. It is imperative that the clinical significance of the CTC test also be examined in Japan. METHODS: Using the CellSearch System, CTC levels were evaluated in 57 healthy individuals and patients with benign breast disease; 30 patients with primary breast cancer (stages 1-3); and 38 patients with metastatic breast cancer. First, the relationship between CTC levels and the presence of metastasis was examined using a cutoff score of 2 CTCs per 7.5 ml whole blood. Then, the patients with metastatic breast cancer were divided into two groups, using a cutoff score of 5 CTCs per 7.5 ml blood, and progression-free survival (PFS) and overall survival (OS) were compared in the two groups. RESULTS: When the clinical cutoff score was set at 2 CTCs per 7.5 ml blood, 0% of the healthy individuals and patients with benign breast disease (0/57), 3.3% of the patients with primary breast cancer (1/30), and 50% of the patients with metastatic breast cancer (19/38) were identified as as having 2 CTCs per 7.5 ml blood. Additionally, with a cutoff score of 5 CTCs, 11 patients were reported to have 5 or more CTCs and both PFS (P = 0.0036) and OS (P = 0.04) were worse for this patient population than for the population with fewer than 5 CTCs. CONCLUSION: As concluded in a similar clinical trial in the United States, for patients with breast cancer, measuring CTC levels can be both an accurate indicator of metastases and an important measure of patient prognosis.