Journal Article
. 2003 Sep; 21(18):3469-78.
doi: 10.1200/JCO.2003.02.009.

Detection of isolated tumor cells in bone marrow is an independent prognostic factor in breast cancer

G Wiedswang 1 E Borgen  R Kåresen  G Kvalheim  J M Nesland  H Qvist  E Schlichting  T Sauer  J Janbu  T Harbitz  B Naume  
  • PMID: 12972522
  •     80 citations


Purpose: This study was performed to disclose the clinical impact of isolated tumor cell (ITC) detection in bone marrow (BM) in breast cancer.

Patients And 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.

Conclusion: 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.

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