Prognostic value of disseminated tumor cells in the bone marrow of patients with operable primary breast cancer: a long-term follow-up study

Ann Surg Oncol. 2013 Jun;20(6):1865-71. doi: 10.1245/s10434-012-2814-4. Epub 2012 Dec 21.

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.

MeSH terms

  • Adult
  • Bone Marrow / pathology*
  • Breast Neoplasms / metabolism
  • Breast Neoplasms / pathology*
  • Breast Neoplasms / surgery
  • Disease-Free Survival
  • Female
  • Follow-Up Studies
  • Humans
  • Kaplan-Meier Estimate
  • Lymphatic Metastasis
  • Middle Aged
  • Mucin-1 / metabolism*
  • Neoplasm Recurrence, Local / metabolism
  • Neoplasm Recurrence, Local / pathology*
  • Neoplasm Staging
  • Neoplastic Cells, Circulating / metabolism*
  • Proportional Hazards Models
  • Time Factors

Substances

  • MUC1 protein, human
  • Mucin-1