December 11, 2010
CTCs Predict Poor Outcome From Blood Stem Cell Transplantation Therapy For Metastatic Breast Cancer
Metastatic breast cancer patients who had circulating tumor cells (CTCs) in their blood before or after high-dose chemotherapy (HDCT) followed by autologous stem cell transplantation had poor outcomes, according to researchers from the University of Texas MD Anderson Cancer Center.
Patients with CTCs in their blood before chemotherapy treatment had reduced survival and those with these cells in their blood after the stem cell transplant recurred faster and died earlier. These findings were presented at the 33rd Annual CTRC-AACR San Antonio Breast Cancer Symposium, held Dec 8-12.While it has been known that CTCs in metastatic breast cancer are linked to cancer recurrence and lower survival, this study adds several new insights, the researchers said. One is that the process of collecting hematopoietic progenitor cells appears to recruit CTCs from bone marrow into the blood, and the other is that these CTCs are likely to be responsible for cancer recurrence.
"Our group had previously shown that metastatic breast cancer patients with CTCs in their blood relapsed faster and now we see that these same cells can be recruited from bone marrow and that they may have the same effect on disease outcome," said the lead researcher Hui Gao, Ph.D., a research scientist working in the laboratory of James M. Reuben, Ph.D.
"Furthermore, some CTCs seem to have the characteristic markings of stem-like cells, but we don't know yet if they are cancer stem cells," Gao said.
The 21 patients included in this study were younger women (average age of 44) diagnosed with metastatic breast cancer who were offered high-dose chemotherapy followed by stem cell transplant. Before chemotherapy, patients were given a growth factor treatment to recruit hematopoietic progenitor cells from bone marrow, then the cells were harvested from their blood.
CTCs were found in six patients before transplant and in nine patients one month after. Researchers determined that more than five CTCs at baseline was associated with shorter overall survival and that five or more CTCs after transplant was linked to both shorter relapse-free survival and overall survival.
The process of using growth factors to mobilize hematopoietic stem cells also appears to mobilize some CTCs that have lost their epithelial properties and undergo mesenchymal transition, according to the researchers. Such cells are not easily detected by the conventional CTC detection assays and the importance of this observation might be overlooked by the clinicians.
High-dose chemotherapy followed by stem cell transplant did reduce the number of existing CTCs in some patients, but increased CTCs in other patients. Patients who recurred faster and had shorter survival had a higher percentage of epithelial cells with stem-like markings mixed in with blood hematopietic progenitor cells that were mobilized by the growth factor to enter blood stream.
"When we enriched for hematopoietic progenitor cells, we found some CTCs within the milieu of cells we collected," Gao said.
In some cases, mobilization may have facilitated the release of cancer stem cells from the bone marrow that were associated with shorter relapse-free survival. However, mobilized CTCs can be removed from the final transplanted product using a procedure to positively select for CD34+ hematopoietic progenitor cells. This procedure may account for the fact that the patients with low CTCs did well.
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