Prognostic significance of tumor cell detection in comparison to nodal status in 1026 patients with primary breast cancer

Consensus about risk-adapted systemic therapy of node negative breast cancer patients remains difficult because of the lack of reliable prognostic factors. Approximately 30% of nodal-negative breast cancer patients will relapse within 10 years and 10-20% of those with distant metastases will be lymph node-negative at the time of surgery. Evaluation of potentially new prognostic factors, therefore, have to concentrate on this issue. Tumor cell detection (TCD) in bone marrow indicates the presence of tumor cell shedding in malignant disease. In a prospective study we examined TCD immunocytologically in 1026 women who underwent primary breast cancer surgery at the Women's Hospital of the University of Heidelberg (1985-1995). Bone marrow aspiration at two sites on each anterior iliac crest was performed immediately after surgery under general anesthesia. Most patients received some type of systemic adjuvant treatment. The monoclonal antibody 2 E11, directed against the breast-mucin TAG 12, was used to detect tumor cells in bone marrow samples. The statistical analysis of follow-up data included Kaplan-Meier estimation of survival curves, logrank tests and multivariate Cox regression analysis with stratification by adjuvant therapy. TCD was positive in 53% of 480 node positive and in 31% of 546 node-negative patients. TCD correlated significantly with larger tumors (p < 0.001), lymph node involvement (p < 0.001), undifferentiated tumor grade (p < 0.006), and postmenopausal status (p = 0.018). After a median follow-up of 42 months tumor cell positive patients showed a reduced relapse free and overall survival (p(0.001). Multivariate Cox regression analysis showed that TCD was an independent prognostic factor superior to lymph node status, tumor stage, and grading. Especially in tumors less than 2 cm diameter TCD was the most powerful predictor of outcome (TCD: p < 0.001, RR 12.3; Nodal status: p = 0.096, RR 2.34). Tumor cell detection in bone marrow of breast cancer patients is a highly significant prognostic factor with a negligible morbidity (in comparison to nodal axillary dissection) and is the best marker of dissemination in node negative disease. Prospective randomized studies should be performed to determine whether axillary node dissection might be replaced by bone marrow aspiration and TCD in a defined subgroup of patients with small tumors.