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


METHODS
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.


CONCLUSIONS
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.
Kasimir-Bauer
S
S
University of Essen Medical School, Department of Internal Medicine (Cancer Research), West German Cancer Center, D-45122 Essen, Germany. sabine.kasimir-bauer@uni-essen.de
Mayer
S
S
Bojko
P
P
Borquez
D
D
Neumann
R
R
Seeber
S
S
D000903:Antibiotics, Antineoplastic / Q000627:therapeutic use; D000964:Antimetabolites, Antineoplastic / Q000627:therapeutic use; D000970:Antineoplastic Agents / Q000627:therapeutic use*; D018906:Antineoplastic Agents, Alkylating / Q000627:therapeutic use; D000972:Antineoplastic Agents, Phytogenic / Q000627:therapeutic use; D001854:Bone Marrow Cells / Q000166:cytology*; D001943:Breast Neoplasms / Q000188:drug therapy* / Q000473:pathology* / Q000532:radiotherapy; D002470:Cell Survival; D002945:Cisplatin / Q000627:therapeutic use; D003131:Combined Modality Therapy; D003520:Cyclophosphamide / Q000627:therapeutic use; D000077143:Docetaxel; D004305:Dose-Response Relationship, Drug; D004317:Doxorubicin / Q000627:therapeutic use; D004797:Enzyme-Linked Immunosorbent Assay; D015251:Epirubicin / Q000627:therapeutic use; D005260:Female; D005434:Flow Cytometry; D005472:Fluorouracil / Q000627:therapeutic use; D016179:Granulocyte Colony-Stimulating Factor / Q000627:therapeutic use; D006801:Humans; D007150:Immunohistochemistry; D018189:Immunomagnetic Separation; D007633:Keratins / Q000096:biosynthesis; D008875:Middle Aged; D009362:Neoplasm Metastasis; D017239:Paclitaxel / Q000031:analogs & derivatives / Q000627:therapeutic use; D018719:Erb-b2 Receptor Tyrosine Kinases / Q000096:biosynthesis; D012307:Risk Factors; D013234:Stem Cells / Q000166:cytology* / Q000378:metabolism; D043823:Taxoids; D013997:Time Factors; D014407:Tumor Cells, Cultured
D000903:Antibiotics, Antineoplastic; D000964:Antimetabolites, Antineoplastic; D000970:Antineoplastic Agents; D018906:Antineoplastic Agents, Alkylating; D000972:Antineoplastic Agents, Phytogenic; D002945:Cisplatin; D003520:Cyclophosphamide; D000077143:Docetaxel; D004317:Doxorubicin; D015251:Epirubicin; D005472:Fluorouracil; D016179:Granulocyte Colony-Stimulating Factor; D007633:Keratins; D017239:Paclitaxel; D018719:Erb-b2 Receptor Tyrosine Kinases; D043823:Taxoids