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 chemotherapy.

Abstract

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.

• Authors: S Kasimir-Bauer, S Mayer, P Bojko, D Borquez, R Neumann, S Seeber
• Journal: Clinical cancer research : an official journal of the American Association for Cancer Research (Clin Cancer Res) Vol. 7 Issue 6 Pg. 1582-9 (Jun 2001) ISSN: 1078-0432 [Print] United States
• PMID: 11410494 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)

Chemical References

• Antibiotics, Antineoplastic
• Antimetabolites, Antineoplastic
• Antineoplastic Agents
• Antineoplastic Agents, Alkylating
• Antineoplastic Agents, Phytogenic
• Taxoids
• Granulocyte Colony-Stimulating Factor
• Docetaxel
• Epirubicin
• Keratins
• Doxorubicin
• Cyclophosphamide
• Receptor, ErbB-2
• Paclitaxel
• Cisplatin
• Fluorouracil

Topics

• Antibiotics, Antineoplastic (therapeutic use)
• Antimetabolites, Antineoplastic (therapeutic use)
• Antineoplastic Agents (therapeutic use)
• Antineoplastic Agents, Alkylating (therapeutic use)
• Antineoplastic Agents, Phytogenic (therapeutic use)
• Bone Marrow Cells (cytology)
• Breast Neoplasms (drug therapy, pathology, radiotherapy)
• Cell Survival
• Cisplatin (therapeutic use)
• Combined Modality Therapy
• Cyclophosphamide (therapeutic use)
• Docetaxel
• Dose-Response Relationship, Drug
• Doxorubicin (therapeutic use)
• Enzyme-Linked Immunosorbent Assay
• Epirubicin (therapeutic use)
• Female
• Flow Cytometry
• Fluorouracil (therapeutic use)
• Granulocyte Colony-Stimulating Factor (therapeutic use)
• Humans
• Immunohistochemistry
• Immunomagnetic Separation
• Keratins (biosynthesis)
• Middle Aged
• Neoplasm Metastasis
• Paclitaxel (analogs & derivatives, therapeutic use)
• Receptor, ErbB-2 (biosynthesis)
• Risk Factors
• Stem Cells (cytology, metabolism)
• Taxoids
• Time Factors
• Tumor Cells, Cultured