Lack of effect of adjuvant chemotherapy on the elimination of single dormant tumor cells in bone marrow of high-risk breast cancer patients

Purpose: There is an urgent need for markers that can predict the efficacy of adjuvant chemotherapy in patients with solid tumors. This study was desi gned to evaluate whether monitoring of micrometastases in bone marrow can p redict the response to systemic chemotherapy in breast cancer. Patients and Methods: Bone marrow aspirates of 59 newly diagnosed breast ca ncer patients with either inflammatory (n = 23) or advanced (> four nodes i nvolved) disease (n = 36) were examined immunocytochemically with the monoc lonal anticytokeratin (CK) antibody A45-B/B3 (murine immunoglobulin G(1); M icromet, Munich, Germany) before and after chemotherapy with taxanes and an thracyclines. Results: Of 59 patients, 29 (49.2%) and 26 (44.1%) presented with CK-positi ve tumor cells in bone marrow before and after chemotherapy, respectively. After chemotherapy, less than half of the previously CK-positive patients ( 14 of 29 patients; 48.3%) had a CK-negative bone marrow finding, and 11 (36 .7%) of 30 previously CK-negative patients were CK-positive. At a median fo llow-up of 19 months (range, 6 to 39 months), Kaplan-Meier analysis of 55 a ssessable patients revealed a significantly reduced overall survival (P = . 011; log-rank test) if CK-positive cells were detected after chemotherapy. In multivariate analysis, the presence of CK-positive tumor cells in bone m arrow after chemotherapy was an independent predictor for reduced overall s urvival (relative risk = 5.0; P = .016). Conclusion: The cytotoxic agents currently used for chemotherapy in high-ri sk breast cancer patients do not completely eliminate CK-positive tumor cel ls in bone marrow. The presence of these tumor cells after chemotherapy is associated with poor prognosis. Thus, bone marrow monitoring might help pre dict the response to systemic chemotherapy. (C) 2000 by American Society of Clinical Oncology.