title: Evaluation of the prognostic significance of disseminated tumor cells in the bone marrow of primary, non-metastatic breast cancer patients after a 7-year follow-up.
abstract: OBJECTIVE
  About 30% of primary, non-metastatic breast cancer patients show a relapse of the disease years after first diagnosis, probably due to early tumor cell spread to the bone marrow (BM). For disseminated tumor cells (DTCs) in the BM, tumor cell dormancy, stem cell-like features and discordant receptor status of DTCs as compared to the primary tumor have been described, explaining the failure of conventional therapies. Here, we demonstrate no prognostic impact of DTCs and explain these findings by early bisphosphonate intake.
  
  
  METHODS
  Bone marrow aspirates of 394 patients with first diagnosis of breast cancer diagnosed between July 1997 and February 2003 were evaluated for DTCs, applying immunocytochemistry. In addition to the given therapy including chemotherapy, radiotherapy and anti-hormonal therapy, oral clodronate therapy was recommended for at least 2 years for all DTC-positive patients. BM results were correlated with clinical prognostic factors and overall survival (OS).
  
  
  RESULTS
  Disseminated tumor cells were detected in 163/394 (41%) patients and significantly correlated with a histopathological lobular subtype (p = 0.032) and inversely with HER2 positivity (p = 0.01). After a median follow-up of 7 years, no significant differences with regard to OS could be demonstrated for DTC-positive patients as compared to patients with no DTCs in the BM at first diagnosis (p = 0.156).
  
  
  CONCLUSIONS
  In this study, we demonstrate no prognostic impact of DTCs, contradictory to previous findings. We speculate that the lack of impact of DTC-positivity on OS might be due to early clodronate intake, but further studies will have to prove whether the observed effect can be confirmed.
authors.affiliation: Department of Gynecology and Obstetrics, University Hospital Essen, University of Duisburg-Essen, Hufelandstrasse 55, 45122, Essen, Germany. oliver.hoffmann@uk-essen.de.
authors.forename: O
authors.identifier: http://orcid.org/0000-0003-3093-9054
authors.initials: O
authors.lastname: Hoffmann
authors.affiliation: Department of Gynecology and Obstetrics, University Hospital Essen, University of Duisburg-Essen, Hufelandstrasse 55, 45122, Essen, Germany.
authors.forename: I A
authors.initials: IA
authors.lastname: Schroer-Zuendorf
authors.affiliation: Department of Gynecology and Obstetrics, University Hospital Essen, University of Duisburg-Essen, Hufelandstrasse 55, 45122, Essen, Germany.
authors.forename: S
authors.initials: S
authors.lastname: Kasimir-Bauer
authors.affiliation: Department of Gynecology and Obstetrics, University Hospital Essen, University of Duisburg-Essen, Hufelandstrasse 55, 45122, Essen, Germany.
authors.forename: C
authors.initials: C
authors.lastname: Oberhoff
authors.affiliation: Department of Gynecology and Obstetrics, University Hospital Essen, University of Duisburg-Essen, Hufelandstrasse 55, 45122, Essen, Germany.
authors.forename: R
authors.initials: R
authors.lastname: Kimmig
authors.affiliation: Department of Gynecology and Obstetrics, University Hospital Essen, University of Duisburg-Essen, Hufelandstrasse 55, 45122, Essen, Germany.
authors.forename: M
authors.initials: M
authors.lastname: Heubner
mesh_terms: D000328:Adult; D000368:Aged; D050071:Bone Density Conservation Agents / Q000627:therapeutic use; D001853:Bone Marrow / Q000473:pathology*; D001943:Breast Neoplasms / Q000188:drug therapy / Q000378:metabolism / Q000473:pathology*; D017024:Chemotherapy, Adjuvant / Q000379:methods; D004002:Clodronic Acid / Q000627:therapeutic use; D005260:Female; D005500:Follow-Up Studies; D006801:Humans; D007150:Immunohistochemistry; D008875:Middle Aged; D009364:Neoplasm Recurrence, Local / Q000473:pathology*; D009360:Neoplastic Cells, Circulating / Q000378:metabolism; D017063:Outcome Assessment, Health Care; D011379:Prognosis
chemical_list: D050071:Bone Density Conservation Agents; D004002:Clodronic Acid
keywords: Adjuvant therapy; Clodronate; Disseminated tumor cells; Early breast cancer