title: Persistence of disseminated tumor cells in the bone marrow of breast cancer patients predicts increased risk for relapse--a European pooled analysis.
abstract: BACKGROUND
  The prognostic significance of disseminated tumor cells (DTC) in bone marrow (BM) of breast cancer patients at the time of primary diagnosis has been confirmed by a large pooled analysis. In view of the lack of early indicators for secondary adjuvant treatment, we here evaluated whether the persistence of DTCs after adjuvant therapy increases the risk of subsequent relapse and death.
  
  
  METHODS
  Individual patient data from 676 women with primary diagnosis of early breast cancer stages I-III from 3 follow-up studies were pooled. During clinical follow-up, patients underwent BM aspiration (BMA) to determine the presence of DTC. Tumor cells were detected by the standardized immunoassays. Univariate and multivariable proportional hazards models were estimated to assess the prognostic significance of DTC for disease-free survival (DFS) and overall survival (OS).
  
  
  RESULTS
  Patients were followed for a median of 89 months. BMA was performed at median 37 months after diagnosis of breast cancer. At follow-up BMA, 15.5% of patients had DTCs. The presence of DTC was an independent indicator of poor prognosis for DFS, distant DFS (DDFS), cancer-specific survival, and OS during the first 5 years following cancer diagnosis (log-rank test P < 0.001 values for all investigated endpoints).
  
  
  CONCLUSIONS
  Among breast cancer patients, persistent DTCs during follow-up significantly predicted the increased risk for subsequent relapse and death. Analysis of DTC might serve as a clinically useful monitoring tool and should be tested as an indicator for secondary adjuvant treatment intervention within clinical trials.
authors.affiliation: Frauenklinik der Heinrich-Heine-Universitat, Düsseldorf, Germany. wolfgang.janni@med.uni-duesseldorf.de
authors.forename: Wolfgang
authors.initials: W
authors.lastname: Janni
authors.forename: Florian D
authors.initials: FD
authors.lastname: Vogl
authors.forename: Gro
authors.initials: G
authors.lastname: Wiedswang
authors.forename: Marit
authors.initials: M
authors.lastname: Synnestvedt
authors.forename: Tanja
authors.initials: T
authors.lastname: Fehm
authors.forename: Julia
authors.initials: J
authors.lastname: Jückstock
authors.forename: Elin
authors.initials: E
authors.lastname: Borgen
authors.forename: Brigitte
authors.initials: B
authors.lastname: Rack
authors.forename: Stephan
authors.initials: S
authors.lastname: Braun
authors.forename: Harald
authors.initials: H
authors.lastname: Sommer
authors.forename: Erich
authors.initials: E
authors.lastname: Solomayer
authors.forename: Klaus
authors.initials: K
authors.lastname: Pantel
authors.forename: Jahn
authors.initials: J
authors.lastname: Nesland
authors.forename: Klaus
authors.initials: K
authors.lastname: Friese
authors.forename: Bjørn
authors.initials: B
authors.lastname: Naume
mesh_terms: D000368:Aged; D001706:Biopsy; D001853:Bone Marrow / Q000473:pathology*; D019046:Bone Marrow Neoplasms / Q000209:etiology / Q000556:secondary; D001943:Breast Neoplasms / Q000175:diagnosis* / Q000401:mortality / Q000473:pathology*; D002277:Carcinoma / Q000175:diagnosis* / Q000401:mortality / Q000473:pathology*; D005060:Europe; D005260:Female; D006801:Humans; D007150:Immunohistochemistry; D008875:Middle Aged; D009360:Neoplastic Cells, Circulating / Q000473:pathology*; D011237:Predictive Value of Tests; D011379:Prognosis; D012008:Recurrence; D012307:Risk Factors