Purpose: This study was performed to disclose the clini-cal 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 nodepositive 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 diseasefree 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