Prognostic Value of Disseminated Tumor Cells in the Bone Marrow of Patients with Operable Primary Breast Cancer: A Long-term Follow-up Study

Abstract

Detection of disseminated tumor cells (DTC) in primary breast cancer (BC) patients' bone marrow (BM) seems to be a surrogate marker of tumor spread and an independent prognostic factor for disease-free and overall survival. Here we present the largest single-center cohort of patients (n=1378) with the longest observation time (median 82.0months). Immunocytochemical staining was performed using murine monoclonal antibody 2E11 with the avidin-biotin complex technique. At primary surgery, 49% of patients showed MUC-1 positive cells inside their BM. Patients without BM DTC had significantly more often T1-tumors (P=0.007) with less often affected axillary lymph nodes (P<0.001). We observed a significantly higher incidence of distant metastases in DTC positive patients (P<0.001). This leads to a reduced disease-free survival (P<0.0001). Furthermore, in DTC positive patients there was a higher mortality rate and, accordingly, a reduced overall survival (P<0.0001). Due to the presence of BM DTC, patients with a clinically poorer outcome can be identified at primary surgery. We therefore suggest that DTC analysis can be used as a prognostic factor and monitoring tool in clinical trials. Future study concepts relating to DTC should aim at identification of BC patients who may profit from adjuvant systemic therapy.