title: Detection of isolated tumor cells in bone marrow is an independent prognostic factor in breast cancer.
abstract: OBJECTIVE
  This study was performed to disclose the clinical impact of isolated tumor cell (ITC) detection in bone marrow (BM) in breast cancer.
  
  
  METHODS
  BM aspirates were collected from 817 patients at primary surgery. Tumor cells in BM were detected by immunocytochemistry using anticytokeratin antibodies (AE1/AE3). Analyses of the primary tumor included histologic grading, vascular invasion, and immunohistochemical detection of c-erbB-2, cathepsin D, p53, and estrogen receptor (ER)/progesterone receptor (PgR) expression. These analyses were compared with clinical outcome. The median follow-up was 49 months.
  
  
  RESULTS
  ITC were detected in 13.2% of the patients. The detection rate rose with increasing tumor size (P =.011) and lymph node involvement (P <.001). Systemic relapse and death from breast cancer occurred in 31.7% and 26.9% of the BM-positive patients versus 13.7% and 10.9% of BM-negative patients, respectively (P <.001). Analyzing node-positive and node-negative patients separately, ITC positivity was associated with poor prognosis in the node-positive group and in node-negative patients not receiving adjuvant therapy (T1N0). In multivariate analysis, ITC in BM was an independent prognostic factor together with node, tumor, and ER/PgR status, histologic grade, and vascular invasion. In separate analysis of the T1N0 patients, histologic grade was independently associated with both distant disease-free survival (DDFS) and breast cancer-specific survival (BCSS), ITC detection was associated with BCSS, and vascular invasion was associated with DDFS.
  
  
  CONCLUSIONS
  ITC in BM is an independent predictor of DDFS and BCSS. An unfavorable prognosis was observed for node-positive patients and for node-negative patients not receiving systemic therapy. A combination of several independent prognostic factors can classify subgroups of patients into excellent and high-risk prognosis groups.
authors.affiliation: Surgical Department, Ullevål University Hospital, Kirkeveien 165, N-0407 Oslo, Norway. gro.wiedswang@ulleval.no
authors.forename: G
authors.initials: G
authors.lastname: Wiedswang
authors.forename: E
authors.initials: E
authors.lastname: Borgen
authors.forename: R
authors.initials: R
authors.lastname: Kåresen
authors.forename: G
authors.initials: G
authors.lastname: Kvalheim
authors.forename: J M
authors.initials: JM
authors.lastname: Nesland
authors.forename: H
authors.initials: H
authors.lastname: Qvist
authors.forename: E
authors.initials: E
authors.lastname: Schlichting
authors.forename: T
authors.initials: T
authors.lastname: Sauer
authors.forename: J
authors.initials: J
authors.lastname: Janbu
authors.forename: T
authors.initials: T
authors.lastname: Harbitz
authors.forename: B
authors.initials: B
authors.lastname: Naume
mesh_terms: D001707:Biopsy, Needle; D001853:Bone Marrow / Q000473:pathology*; D001943:Breast Neoplasms / Q000401:mortality / Q000473:pathology* / Q000628:therapy; D003131:Combined Modality Therapy; D018572:Disease-Free Survival; D005260:Female; D006801:Humans; D007150:Immunohistochemistry; D008207:Lymphatic Metastasis; D015999:Multivariate Analysis; D009362:Neoplasm Metastasis; D009364:Neoplasm Recurrence, Local; D011379:Prognosis; D015996:Survival Rate