title: Prognostic value of disseminated tumor cells in the bone marrow of patients with operable primary breast cancer: a long-term follow-up study.
abstract: BACKGROUND
  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.
  
  
  METHODS
  Here we present the largest single-center cohort of patients (n = 1378) with the longest observation time (median 82.0 months). Immunocytochemical staining was performed using murine monoclonal antibody 2E11 with the avidin-biotin complex technique.
  
  
  RESULTS
  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).
  
  
  CONCLUSIONS
  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.
authors.affiliation: Breast Unit, University of Heidelberg, Heidelberg, Germany.
authors.forename: Christoph
authors.initials: C
authors.lastname: Domschke
authors.forename: Ingo J
authors.initials: IJ
authors.lastname: Diel
authors.forename: Stefan
authors.initials: S
authors.lastname: Englert
authors.forename: Silvia
authors.initials: S
authors.lastname: Kalteisen
authors.forename: Luisa
authors.initials: L
authors.lastname: Mayer
authors.forename: Joachim
authors.initials: J
authors.lastname: Rom
authors.forename: Joerg
authors.initials: J
authors.lastname: Heil
authors.forename: Christof
authors.initials: C
authors.lastname: Sohn
authors.forename: Florian
authors.initials: F
authors.lastname: Schuetz
mesh_terms: D000328:Adult; D001853:Bone Marrow / Q000473:pathology*; D001943:Breast Neoplasms / Q000378:metabolism / Q000473:pathology* / Q000601:surgery; D018572:Disease-Free Survival; D005260:Female; D005500:Follow-Up Studies; D006801:Humans; D053208:Kaplan-Meier Estimate; D008207:Lymphatic Metastasis; D008875:Middle Aged; D018396:Mucin-1 / Q000378:metabolism*; D009364:Neoplasm Recurrence, Local / Q000378:metabolism / Q000473:pathology*; D009367:Neoplasm Staging; D009360:Neoplastic Cells, Circulating / Q000378:metabolism*; D016016:Proportional Hazards Models; D013997:Time Factors
chemical_list: C060192:MUC1 protein, human; D018396:Mucin-1