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Survival of Tumor Cells in Stem Cell Preparations and Bone Marrow of Patients with High-Risk or Metastatic Breast Cancer after Receiving Dose-intensive or High-Dose Chemotherapy¹

University of Essen Medical School, Department of Internal Medicine (Cancer Research), West German Cancer Center, D-45122 Essen [S. K-B., S. M., P. B., D. B., S. S.], and Bayer Vital GmbH, D-51368 Leverkusen [R. N.], Germany

Purpose: We evaluated whether dose-intensive or high-dose chemotherapy can eliminate micrometastases in high-risk breast cancer patients.

Experimental Design: We monitored cytokeratin (CK)/17-1A positive cells in the bone marrow (BM) and peripheral blood stem cells (PBSC) and studied Her-2/neu serum levels of patients with locally advanced (n = 13; group 1) and metastatic breast cancer (n = 30; group 2) using immunomagnetic separation, immunocytochemistry, and ELISA.

Results: CK+ cells were found in the BM of 3 of 13 (23%) group 1 patients before but not after chemotherapy, resulting in an overall survival (OS) of 92% after a median follow-up of 33 months. Contamination of PBSC in 2 of 9 (22%) patients was not associated with decreased survival. In group 2 patients, the CK+ rate was 60% (18 of 30 patients) before and 40% (4 of 10 patients) after therapy with an OS rate of 43% after 29 months. PBSC samples were positive in 7 of 24 (29%) patients. CK+ BM and PBSC led to a rapid progress and short OS, whereas tumor cell-free BM and PBSC resulted in a mean OS of 30 months. The antigen 17-1A was detected on most CK+ cells in both patient groups before therapy, on all of CK+ PBSC, and on CK+ cells in group 2 patients after therapy. Increased Her-2/neu levels were found in group 2 patients before chemotherapy.

Conclusion: Micrometastatic cells are present in PBSC grafts and can survive even high-dose chemotherapy. The presence of immunotherapeutic target antigens supports the idea that a combined chemoimmunotherapy might be successful in eliminating minimal residual disease.

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