Prognostic relevance of circulating tumor cells (CTCs) in peripheral blood of breast cancer patients before and after adjuvant chemotherapy – translational research program of the German SUCCESS-trial.

Abstract

Abstract #303

Background:
The detection of Disseminated Tumor Cells in the Bone Marrow (BM) of Breast Cancer patients has shown prognostic significance in all stages of the disease. An alternative towards BM examination could be the analysis of peripheral blood for Circulating Tumor Cells (CTCs), which has demonstrated prognostic significance in metastatic disease. We analyzed peripheral blood samples from pts. Before and after adjuvant taxane-based chemotherapy as part of the translational research program of the German SUCCESS-trial.
Methods: Peripheral blood samples (23 ml each) from 1500 N+ and high risk N- breast cancer pts were analyzed for the presence of CTCs with the CellSearchSystem (Veridex, USA) before and after adjuvant chemotherapy. After automated immunomagnetic enrichment with an anti-Epcam-antibody, cells are labelled with anti-cytokeratin (8,18,19) and anti-CD45 antibodies to distinguish between epithelial cells and leukocytes. Samples are screened automatedly and positive events are visualised on a screen for re-evaluation.
Results: In143 pts (10 %) more than 1 CTC was detected before the start of systemic treatment (mean 14, range 2-827). 2 CTCs were found in 4 % of pts, 3 % had 3-5 CTCs and 1 % 6-10 and >10 CTCs, resp. The presence of CTCs did not correlate with tumor size (p=.32), grading (p=.36), hormonal status (p=.28) or Her2 status of the primary tumor (p=.82), but with the presence of lymph node metastases (p=.003). As negative control, three of 74 healthy individuals 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 % turned positive after chemotherapy (n=115, p=.42).
21 recurrences have been reported during a median follow-up time of 12 months, and 7 pts have died of their disease. While detection of CTCs before systemic treatment did not show prognostic relevance for DFS (p=.89) and OAS (p=.71), presence of CTCs after chemotherapy was a significant predictor for both reduced DFS (p=.04) and OAS (p=.03).
Conclusions:
Our preliminary results demonstrate prognostic relevance of the presence of CTCs after adjuvant chemotherapy for the first time. Even in the adjuvant setting as well as during follow up, the examination of CTCs could be a valuable tool for monitoring the disease and the effectiveness of therapies. Longer follow-up of the SUCCESS-trial will have to be awaited to confirm these findings.

Citation Information: Cancer Res 2009;69(2 Suppl):Abstract nr 303.