title: The persistence of isolated tumor cells in bone marrow from patients with breast carcinoma predicts an increased risk for recurrence.
abstract: BACKGROUND
  The prognostic significance of isolated tumor cells (ITCs) in bone marrow (BM) from patients with breast carcinoma at the time of their primary diagnosis recently was been confirmed by a large pooled analysis. If the persistence of ITCs after adjuvant therapy confers a similar risk for recurrence, then it would be an indication to consider secondary adjuvant therapy.
  
  
  METHODS
  The authors analyzed BM aspirates from 228 patients during recurrence-free follow-up at a median interval +/- standard deviation (SD) of 21.3 +/- 29.1 months after a primary diagnosis of breast carcinoma (pathologic T1 [pT1]-pT2, pN0-pN3, pM0). Carcinoma cells were detected using a standardized immunoassay with monoclonal antibody A45-B/B3 directed against cytokeratin (CK). Patients were followed for a median +/- SD of 49.8 +/- 32.1 months after their primary diagnosis.
  
  
  RESULTS
  Persistent ITCs in BM were detected in 12.7% of patients (n=29 patients). Positive BM status was more frequent (15.7%) within the first 21 months after primary diagnosis than after a follow-up > 21 months (9.7%). The Kaplan-Meier estimate for mean recurrence-free survival was 149.7 months (95% confidence interval [95% CI], 139.6-159.8 months) in patients with negative BM status and 86.5 months (95% CI, 65.7-107.4 months; P=0.0003) in patients with positive BM status at the time patients underwent follow-up BM aspiration. Patients who were without evidence of persistent ITCs had a significantly longer overall survival (162.1 months; 95% CI, 152.1-172.0 months) compared with patients who had positive BM status (overall survival, 98.7 months; 95% CI, 79.7-117.9 months; P=0.0008). In multivariate Cox regression analysis that included BM status, tumor size, lymph node status, and histopathologic grade, evidence of ITCs was an independent significant predictor for reduced disease-free survival (relative risk [RR], 4.57; P <0.0001) and overall survival (RR, 5.57; P=0.002). Persistent ITCs had the greatest prognostic relevance when they were detected between 25 months and 42 months after primary diagnosis (RR, 7.68).
  
  
  CONCLUSIONS
  Evidence of persistent ITCs in BM from patients with breast carcinoma indicated an increased risk for subsequent recurrence. Prospective trials should investigate the benefit of secondary adjuvant treatment on the basis of BM marrow status.
authors.affiliation: I. Frauenklinik, Klinikum der Ludwig-Maximilians-Universtitaet, Muenchen, Germany. janni@fk-i.med.uni-muenchen.de
authors.forename: Wolfgang
authors.initials: W
authors.lastname: Janni
authors.forename: Brigitte
authors.initials: B
authors.lastname: Rack
authors.forename: Christian
authors.initials: C
authors.lastname: Schindlbeck
authors.forename: Barbara
authors.initials: B
authors.lastname: Strobl
authors.forename: Dorothea
authors.initials: D
authors.lastname: Rjosk
authors.forename: Stephan
authors.initials: S
authors.lastname: Braun
authors.forename: Harald
authors.initials: H
authors.lastname: Sommer
authors.forename: Klaus
authors.initials: K
authors.lastname: Pantel
authors.forename: Bernd
authors.initials: B
authors.lastname: Gerber
authors.forename: Klaus
authors.initials: K
authors.lastname: Friese
mesh_terms: D001853:Bone Marrow / Q000378:metabolism / Q000473:pathology*; D001943:Breast Neoplasms / Q000401:mortality / Q000473:pathology*; D018572:Disease-Free Survival; D005260:Female; D005500:Follow-Up Studies; D006801:Humans; D007150:Immunohistochemistry; D007633:Keratins / Q000032:analysis; D008875:Middle Aged; D009362:Neoplasm Metastasis; D009364:Neoplasm Recurrence, Local; D012044:Regression Analysis; D012306:Risk; D015996:Survival Rate
chemical_list: D007633:Keratins