Prognostic relevance of circulating tumor cells (CTCs) in peripheral blood of breast cancer patients before and after adjuvant chemotherapy: The German SUCCESS-Trial

Abstract

503 Background: The prognostic significance of CTCs in metastatic breast cancer has been demonstrated. If the presence of CTCs in early breast cancer would also predict an increased risk for relapse, this method might be used as an early marker for treatment efficacy and risk for disease recurrence. Methods: As part of the translational research project of the German SUCCESS-trial, we analyzed 23ml of peripheral blood from 1,500 N+ and high risk N- breast cancer pts before and after adjuvant taxane-based chemotherapy. The presence of CTCs was assessed with the CellSearchSystem (Veridex, USA). After immunomagnetic enrichment with an anti-Epcam-antibody, cells were labeled with anti-cytokeratin (8,18,19) and anti-CD45 antibodies to distinguish between epithelial cells and leukocytes. Results: In 10% of pts (n=143) >1 CTC was detected before the start of systemic treatment (mean 14, range 2–827). While we found 2 CTCs in 4% of pts, 3% had 3–5 CTCs and 1% 6–10 and >10 CTCs respectively. The presence of CTCs did not correlate with tumor size (p=0.32), grading (p=0.36), hormonal status (p=0.28) or HER2/neu status of the primary tumor (p=0.82), but with the presence of lymph node metastases (p=0.003). Three of 74 individuals without malignant disease (4%) showed more than 1 CTC. After completion of chemotherapy, 9% of pts (n=130) presented with >1 CTC (mean 6, range 2–124). Of those initially CTC positive, 10% remained positive (n=15), whereas of those initially CTC negative, 8% returned with a positive test (n=115, p=0.42). 21 recurrences occurred during a median follow-up of 12 months and 7 pts died of their disease. While the presence of CTCs before systemic treatment did not show prognostic relevance for DFS (p=0.89) and OAS (p=0.71), persistence of CTCs after chemotherapy was a significant predictor for both reduced DFS (p=0.04) and OAS (p=0.03). Conclusions: In a considerable number of pts CTCs in peripheral blood can be detected after the completion of chemotherapy. Preliminary results demonstrate a prognostic relevance of persisting CTCs after chemotherapy, thus indicating a potential role for treatment monitoring in early breast cancer. Longer follow-up of the SUCCESS-trial will have to be awaited to confirm these findings. Author Disclosure Employment or Leadership Consultant or Advisory Role Stock Ownership Honoraria Research Expert Testimony Other Remuneration Veridex Veridex Veridex Veridex