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!
First-time reconstruction of infectious bat influenza viruses
25.10.2016 | Universitätsklinikum Freiburg
The nanostructured cloak of invisibility
25.10.2016 | Max-Planck-Institut für Intelligente Systeme
Terahertz excitation of selected crystal vibrations leads to an effective magnetic field that drives coherent spin motion
Controlling functional properties by light is one of the grand goals in modern condensed matter physics and materials science. A new study now demonstrates how...
Researchers from the Institute for Quantum Computing (IQC) at the University of Waterloo led the development of a new extensible wiring technique capable of controlling superconducting quantum bits, representing a significant step towards to the realization of a scalable quantum computer.
"The quantum socket is a wiring method that uses three-dimensional wires based on spring-loaded pins to address individual qubits," said Jeremy Béjanin, a PhD...
In a paper in Scientific Reports, a research team at Worcester Polytechnic Institute describes a novel light-activated phenomenon that could become the basis for applications as diverse as microscopic robotic grippers and more efficient solar cells.
A research team at Worcester Polytechnic Institute (WPI) has developed a revolutionary, light-activated semiconductor nanocomposite material that can be used...
By forcefully embedding two silicon atoms in a diamond matrix, Sandia researchers have demonstrated for the first time on a single chip all the components needed to create a quantum bridge to link quantum computers together.
"People have already built small quantum computers," says Sandia researcher Ryan Camacho. "Maybe the first useful one won't be a single giant quantum computer...
COMPAMED has become the leading international marketplace for suppliers of medical manufacturing. The trade fair, which takes place every November and is co-located to MEDICA in Dusseldorf, has been steadily growing over the past years and shows that medical technology remains a rapidly growing market.
In 2016, the joint pavilion by the IVAM Microtechnology Network, the Product Market “High-tech for Medical Devices”, will be located in Hall 8a again and will...
14.10.2016 | Event News
14.10.2016 | Event News
12.10.2016 | Event News
25.10.2016 | Life Sciences
24.10.2016 | Earth Sciences
24.10.2016 | Life Sciences