Detection of minimal residual disease (MRD) in peripheral blood of primary breast cancer patients: Translational research in the SUCCESS study

Abstract

565 Background: Patients with detection of MRD in bone marrow are known to have an increased risk for recurrence and a poorer clinical outcome. However, peripheral blood would be the preferable compartment to monitor treatment efficacy due to increased feasibility. The translational research program of the German SUCCESS-trial was established to evaluate MRD in peripheral blood at 4 different time points during adjuvant systemic treatment of breast cancer patients. Here first results of the detection of MRD at primary diagnosis and after adjuvant chemotherapy will be presented. Patients and Methods: Cells were separated by Ficoll-Hypaque density- gradient centrifugation followed by labelling of epithelial cells with the anti-cytokeratine-antibody A45-B/B3 (directed against cytokeratines 8, 18 and 19) and immunohistochemically staining with neu-fuchsin. All preparations were screened by two independent persons. Results: 328 breast cancer patients were analyzed at primary diagnosis. Among those, 133 patients returned for a 2nd blood sampling after completion of adjuvant chemotherapy. Most of the tumors were small (43% pT1, 51% pT2, 4% pT3, 1% pT4) but of intermdediate or unfavourable grade, (G1 7%, G2 48%, G3 45%). 66% of the patients were node-positive (34% pN0, 38% pN1, 20% pN2, 8% pN3) and a positive hormone receptor status was seen in 71%. In 22% the Her2-status was positive. MRD in peripheral blood was found in 31% of all patients before and in 9% after chemotherapy. The mean number of detected cells was 2 (range 1- 9). In 87,2 % of the patients who showed MRD at the first measurement no MRD was detected after chemotherapy. 16% of patients without detection of MRD at primary diagnosis showed MRD after chemotherapy. Neither tumor size (p= 0.624), lymph node metastases (p= 0.450), histopathological grading (p= 0.168), hormone receptor status (p= 0.270) or Her2/neu status of the primary tumor (p= 0.893) correlated with the presence of MRD. Conclusions: The detection of MRD in peripheral blood can be widely used and is suitable for repeated measurements. Further follow-up will show, if this method can be used for risk stratification and monitoring of treatment efficacy in adjuvant breast cancer. No significant financial relationships to disclose.