Metastatic breast cancer patients whose blood contains circulating tumor cells (CTCs) before or after treatment with high-dose chemotherapy and blood stem cell transplant have shorter survival periods, according to a new study by researchers at The University of Texas MD Anderson Cancer Center in Houston.
The findings were presented today in a poster session at the 33rd Annual CTRC-AACR San Antonio Breast Cancer Symposium.
In addition, patients with higher percentages of epithelial cells, or the presence of a specific cellular transition, had higher chances for relapse.
"Building on the information from this study, we eventually may be able to use these molecular markers to identify breast cancer patients with a high likelihood of developing metastasis or relapsing. This may allow physicians to design specific treatments to help patients achieve better outcomes," said James M. Reuben, Ph.D., professor in MD Anderson's Department of Hematopathology, and co-corresponding author of the study.
Stem cells have common receptor
High-dose chemotherapy followed by autologous hematopoietic peripheral blood stem cell transplantation (ASCT) offers modest complete response rates for some patients with metastatic breast cancer. However, tumor cells that spread to the bone may be recruited and mobilized along with hematopoietic stem cells to increase a patient's chance of relapse.
"We hypothesized that since the breast tumor cells have the same CXRX4 receptor as hematopoietic stem cells, we might mobilize or recruit tumor cells by using a growth factor proven to mobilize blood stem cells," Reuben said.
Epithelial-to-mesenchymal transition (EMT) is recognized as an important part of metastasis. Epithelial cells line the organs and cavities of the body and usually are not mobile. Mesenchymal cells are mobile and can differentiate into many cell types, for example, to repair injury. EMT has been shown to repress E-cadherin, decrease cell-cell adhesion and increase a cell's capacity to move. An estimated 80 percent of solid tumors are cancers of the epithelial tissue.
Blood examined for epithelial cells, CTC
Aphaeresis was used to harvest blood stem cells from 21 metastatic breast cancer patients before transplantation. To determine levels of CTCs, blood samples were collected before aphaeresis (baseline) and one month after transplantation.
"We used the flow cytometry method of staining for both epithelial and stem cell markers," said Hui Gao, Ph.D., a research scientist in MD Anderson's Department of Hematopathology and co-first author of the study. "Then we enumerated the percentages of epithelial cells and cancer stem cells to see how these correlated with patient survival."
Cells, survival correlated
The median time to follow-up after transplant was 16.4 months. At follow-up, eight women were cancer free, and 13 had relapsed. The median time to relapse was nine months, and median survival was 14.4 months.
CTCs were found in six patients before and in nine patients after transplant. Patients with more than five CTCs before transplant had shorter overall survival. If five or more CTCs were found after transplant, both relapse-free and overall survival times were shorter.
Patients with percentages of CD326+ epithelial cells above the median had shorter relapse-free survival times,10 months versus 23 months. Also, patients with CTCs with mesenchymal features had a shorter relapse-free survival, seven months, compared to those who had CTCs without such features, 23 months.
The researchers hope to carry the research forward into a prospective study in the near future.
"If we really can target CTCs with mesenchymal features, we may be able to control disease much more efficiently," said Naoto T. Ueno, M.D., Ph.D., professor in MD Anderson's Departments of Breast Medical Oncology and Stem Cell Transplantation and Cellular Therapy, and co-corresponding author of the study.
Co-authors with Gao, Reuben and Ueno include, from MD Anderson: Bang-Ning Lee, Ph.D.; Evan Cohen, B.S.; Michelle Davis, M.S.; and Antonio Giordano, M.D. Michael Mego, M.D., Ph.D., National Cancer Institute, Slovak Republic; and Massimo Cristofanilli, M.D., Fox Chase Cancer Center, also contributed to the research.
The research was funded by grants from The University of Texas Health Science Center, the National Cancer Institute, the State of Texas Rare and Aggressive Breast Cancer Research Program and an American Airlines Susan G. Komen Promise Grant.
About MD Anderson
The University of Texas MD Anderson Cancer Center in Houston ranks as one of the world's most respected centers focused on cancer patient care, research, education and prevention. MD Anderson is one of only 40 comprehensive cancer centers designated by the National Cancer Institute. For seven of the past nine years, including 2010, MD Anderson has ranked No. 1 in cancer care in "America's Best Hospitals," a survey published annually in U.S. News & World Report.
Laura Sussman | EurekAlert!
Oestrogen regulates pathological changes of bones via bone lining cells
28.07.2017 | Veterinärmedizinische Universität Wien
Programming cells with computer-like logic
27.07.2017 | Wyss Institute for Biologically Inspired Engineering at Harvard
Spectrally narrow x-ray pulses may be “sharpened” by purely mechanical means. This sounds surprisingly, but a team of theoretical and experimental physicists developed and realized such a method. It is based on fast motions, precisely synchronized with the pulses, of a target interacting with the x-ray light. Thereby, photons are redistributed within the x-ray pulse to the desired spectral region.
A team of theoretical physicists from the MPI for Nuclear Physics (MPIK) in Heidelberg has developed a novel method to intensify the spectrally broad x-ray...
Physicists working with researcher Oriol Romero-Isart devised a new simple scheme to theoretically generate arbitrarily short and focused electromagnetic fields. This new tool could be used for precise sensing and in microscopy.
Microwaves, heat radiation, light and X-radiation are examples for electromagnetic waves. Many applications require to focus the electromagnetic fields to...
Strong light-matter coupling in these semiconducting tubes may hold the key to electrically pumped lasers
Light-matter quasi-particles can be generated electrically in semiconducting carbon nanotubes. Material scientists and physicists from Heidelberg University...
Fraunhofer IPA has developed a proximity sensor made from silicone and carbon nanotubes (CNT) which detects objects and determines their position. The materials and printing process used mean that the sensor is extremely flexible, economical and can be used for large surfaces. Industry and research partners can use and further develop this innovation straight away.
At first glance, the proximity sensor appears to be nothing special: a thin, elastic layer of silicone onto which black square surfaces are printed, but these...
3-D shape acquisition using water displacement as the shape sensor for the reconstruction of complex objects
A global team of computer scientists and engineers have developed an innovative technique that more completely reconstructs challenging 3D objects. An ancient...
26.07.2017 | Event News
21.07.2017 | Event News
19.07.2017 | Event News
28.07.2017 | Health and Medicine
28.07.2017 | Power and Electrical Engineering
28.07.2017 | Life Sciences