Minimal residual disease detection in peripheral blood of primary breast cancer patients – translational research in the SUCCESS-study.

Abstract

Abstract Abstract #5019 Background: The detection of occult tumor cells in the bone marrow of patients with breast cancer has been shown to be an independent predictive and prognostic factor for early disease recurrence and decreased overall survival. However, it is more feasible to monitor treatment efficacy by sampling peripheral blood. The translational research program of the German SUCCESS-trial evaluates Minimal Residual Disease (MRD) in peripheral blood during adjuvant treatment of breast cancer patients. Follow-up results of the detection of MRD at primary diagnosis and after adjuvant chemotherapy (CT) are presented.
 Patients and Methods: Cells were separated by Oncoquick® (Greiner-bio one, Frickenhausen, Germany) followed by labeling of epithelial cells with an anti-cytokeratine-antibody (directed against cytokeratins 8, 18 and 19) and immunocytochemical staining. Every preparation was screened by two independent persons. MRD was defined as one or more cytokeratine-positive cell.
 Results: 1237 breast cancer patients were analyzed at primary diagnosis. After completion of adjuvant CT 655 patients returned for a second blood sampling. The majority of the tumors was small (40.1% pT1, 52.7% pT2, 5.9% pT3, 1.1% pT4) but mostly of intermediate or unfavorable grade, (G1 4.6%, G2 48.9%, G3 46.2%). 65% of the patients were node-positive (35% pN0, 45.6% pN1, 13.8% pN2, 5.7% pN3) and a positive hormone receptor status was seen in 69.1%. In 25.4% the Her2 status was positive. In 20.3% of all patients MRD was found at primary diagnosis. After CT MRD was observed in 15,7%. The mean number of detected cells was 2.3 (range: 1-25) before and 2.1 (range 1-23) after chemotherapy. Neither tumor size (p=0.48, p=0.47), lymph node metastases (p=0.34, p=0.81), histopathological grading (p=0.83, p=0.85) nor hormone receptor status (p=0.72, p=0.65) of the primary tumor correlated with the presence of MRD before or after CT respectively. The Her2/neu status of the primary tumor did not correlate before, but after CT with the presence of the MRD (p=0.63, p=0.08).
 Conclusion: The detection of MRD in peripheral blood can be widely used and is suitable for repeated measurements. Further follow-up of the SUCCESS trial will show this method´s validity for risk stratification and monitoring of treatment efficacy in breast cancer patients. Citation Information: Cancer Res 2009;69(2 Suppl):Abstract nr 5019.