Comparative Analysis of Breast Cancer Contamination in Mobilized and Nonmobilized Hematopoietic Grafts
Available from: Stefan Gluck
- "Are tumor cells also mobilized along with stem cells? In a subsequent study by Ross to compare the contamination between mobilized and nonmobilized grafts, there was no significant difference. Glück et al. in their study found that the contamination dropped significantly after one cycle of induction chemotherapy but further cycles may not be beneficial. "
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ABSTRACT: Circulating tumor cell (CTC) measurement in peripheral blood of patients with breast cancer offers prognostic information. In this review, we will try to identify evidence that could be used for prognosis, predictive power to draw this tool to clinical utility. We reviewed 81 manuscripts, and categorized those in discovery datasets, prognostic factors in metastatic breast cancer, identification of clinical utility in early breast cancer and in novel approaches. With each patient responding differently to chemotherapy, more efficient markers would improve clinical outcome. Current CTC diagnostic techniques use epithelial markers predominantly; however, the most appropriate method is the measurement of circulating DNA. It has been hypothesized that micrometastasis occurs early in the development of tumors. That implies the presence of CTCs in nonmetastatic setting. The origin of stimulus for malignant transformation is yet unknown. The role of microenvironment as a stimulus is also being investigated. It has been shown that CTCs vary in numbers with chemotherapy. The markers, which are followed-up in the primary tumors, are also being studied on the CTCs. There is discordance of the human epidermal growth factor receptor-2 status between the primary tumor and CTCs. This review summarizes our current knowledge about the CTCs. With genetic profiling and molecular characterization of CTCs, it is possible to overcome the diagnostic difficulties. Evidence for clinical utility of CTC as prognostic and predictive marker is increasing. Appropriate patient stratification according to CTC determination among other tests, would make personalized cancer therapy more feasible.
Available from: Luigi Rigacci
- "cells. Breast tumour cells in BM and peripheral blood are capable of in vitro clonogenic growth (Ross et al, 1995), and tumour involvement of either autologous BM graft or PBSC collections has been associated with shorter disease-free and overall survival in stage II–III patients subjected to AT (Harbeck et al, 1994; Pedrazzoli et al, 1997; Hurd & Peters, 1995; Vredenburgh et al, 1997); furthermore, an inverse correlation has been suggested to exist between overall survival after AT and the amount of contaminating cancer cells in the BM (Ross et al, 1996). However, in other studies, tumour contamination of PBSC collections in stage IV patients seemed to have no impact on overall survival (Ybanez et al, 1995). "
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ABSTRACT: There is considerable interest in an autologous transplantation (AT) programme for patients with high-risk breast cancer; however, the issue of the incidence of occult bone marrow (BM) micrometastasis at diagnosis, and the cancer contamination of peripheral blood stem cell (PBSC) collections used for haematological rescue, is still debated. The presence of BM micrometastasis was evaluated in bilateral BM biopsies obtained at diagnosis of 33 patients with stage II/IIIA breast cancer using: (i) a 'nested' reverse transcriptase-polymerase chain reaction (RT-PCR) assay for cytokeratin 19 (K19) mRNA, (ii) histology, and (iii) immunohistochemistry (IHC) analysis with a panel of three monoclonal antibodies. The RT-PCR assay only was used to determine contamination of PBSC collections obtained after priming with recombinant human granulocyte-colony stimulating factor (rhG-CSF). K19 transcripts in one or both BM samples were detected in 48% of patients at diagnosis, with an overall 85% concordance with the results of IHC analysis. On the other hand, 56% of PCR- and IHC-positive BM samples were diagnosed as 'normal' on histological analysis. 57% of patients showed K19 mRNA in at least one PBSC collection; the possibility to have contaminated PBSC collections was significantly higher in patients with K19 positivity in BM at diagnosis. In four patients who had shown K19 positivity in BM and in PBSC collections, immunoselected CD34+ cells used for haematological rescue were K19-negative. There was a trend towards longer relapse free survival (RFS) in patients transplanted with K19-negative PBSC collections as compared to the others. In conclusion, a substantial proportion of patients with high-risk non-metastatic breast cancer present occult BM micrometastasis at diagnosis and also show cancer contamination of PBSC collections used for AT. These might represent a category of patients with poorer prognosis after AT, and possible candidates for more intensive and/or alternative therapeutic regimens, including AT with purged PBSCs.
Available from: Guenter Schlimok
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ABSTRACT: Twenty-one high-risk patients with primary stage II/III breast cancer were treated with high-dose chemotherapy comprising etoposide, ifosfamide, carboplatin and epirubicin (VIC-E). Tumor cells of epithelial origin were analyzed using the monoclonal antibodies CK2 (IgG1) and A45-B/B3 (IgG1) against cytokeratin (CK) components in bone marrow (BM) aspirates prior to chemotherapy, and in peripheral blood stem cell transplants (PBSCT). They were separated after the first (21/21 patients) and the second cycle (16/21 patients) of induction chemotherapy with VIP-E (etoposide, ifosfamide, cisplatin, epirubicin). Preliminary results showed CK positive tumor cells in 40% (14/35) of the analyzed transplants. In 7/12 (58.3%) patients, CK positive tumor cells were detectable in BM prior to treatment. Sixteen patients were separated after the 1st and 2nd cycle of VIP-E. PBSCT of 14/16 patients were assessable for presence of CK positive tumor cells. Our preliminary results demonstrate a lower tumor cell contamination of PBSCT separated after the 2nd cycle of induction therapy (14.3%) compared to contamination after the first induction therapy (64.3%). To date, 4/21 patients have experienced a relapse, and three of these patients had tumor cell positive transplants. Due to the small patient number only a trend towards a superior relapse-free survival in the patient group with CK negative transplants can be shown by Kaplan-Meier analysis.
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