Research collaboration seeks blood test for aggressive breast cancer Well-documented breast cancer tissue collection meets high throughput proteomics to find aggressive-tumor markers in blood
Mammography and biopsies help find breast cancer, but even biopsies won't tell the doctor if the cancer will spread. Now, a two-year research project hopes to find proteins in blood that could alert doctors to patients harboring not just breast cancer, but the nastiest versions of the disease.
The project takes advantage of one of the most comprehensive collections of breast cancer clinical samples, located at the Walter Reed-Windber Clinical Breast Care Project in Washington, D.C. and Windber, Penn., and advanced proteomics technology at the Department of Energy's Pacific Northwest National Laboratory in Richland, Wash. The collaborators are searching for proteins that indicate aggressive breast cancer and that can be detected by a simple blood test. The Department of Defense is providing about $2 million over two years for the study, to be split between the organizations.
"This is an example of expertise in two areas coming together with a plan whose results will be greater than the sum of its parts," says Col. Craig Shriver, M.D., director of the Clinical Breast Care Project.
Although scientists have identified two genes that predispose young women to breast cancer, the vast majority of cases in pre-menopausal women have no obvious genetic link. A blood-borne biomarker would add substantially to the tools available to fight the disease. Many groups are looking for such biomarkers, but access to a 30,000-sample blood and tissue collection, and cutting-edge high-throughput proteomics sets this project apart.
"We're looking for aggressive cancer indicators in pre-menopausal women, and the Army has both the tissue samples and the matching plasma," says cancer biologist Karin Rodland of PNNL, who will work with PNNL's Dick Smith, lead investigator on the proteomics half of the project.
The cancer indicators they are seeking are proteins that arise from genes that have run amuck in cancer. Comparing proteins that work in cancer cells to those in normal cells might reveal how the cells maintain and disperse the cancer throughout the body.
"The genes are the generals giving orders. And those proteins are the foot soldiers who take those orders and accomplish the goal based on the local conditions they find," says Shriver. "Until we know what's going on at the protein level, we don't know how the orders are being applied in the cells."
In addition to finding a tool to fight cancer, Shriver says, the project will likely suggest details of the inner workings of breast cancer cells.
"Hunting for biomarkers is a difficult process," adds geneticist Richard Mural, chief scientific officer at Windber. "But this project will generate unique and new data."
The military might seem an odd place to turn to study what largely afflicts women, but a fifth of the Army's active duty contingent are women, and many of the rest are married to women. In concert with Windber, the Army opened the Clinical Breast Care Project in 2001 to focus solely on breast health to assure the well-being of the force. Since then, they have collected more than 30,000 breast cancer and blood samples from about 4000 female patients.
The clinical sample collection is one key to the project's success, the researchers say. The samples follow the course of the disease, which is one of the best ways to track the growth and spread of cancer, says Mural. Blood samples have been collected before and after surgical treatment, and workers gather the clinical and family histories from the women. Pathologists examine the cancer tissue and the samples are handled and stored under strict protocols, Mural says.
The team will compare the proteins of cancers that stayed in the breast to cancers that spread to lymph nodes, which the scientists hope will reveal proteins that metastasizing tumors use to make their way through the body. The team will also compare diseased tissues from pre- and post-menopausal women. This will ferret out proteins from cancers that hit young women, which are generally more life-threatening than disease that shows up in the years after menopause.
To avoid complications from healthy tissue, Mural's team at Windber will use lasers to carefully snip the cancerous cells from the surrounding breast tissue, and then send the cancer cells to Smith and Rodland for proteomics analysis at the DOE's Environmental Molecular Sciences Laboratory on the PNNL campus. Cutting away the healthy tissue will result in very small samples, but EMSL is set up to study samples that are up to a thousand times smaller than other labs, says Smith.
"PNNL's tissue proteomics is at the cutting edge of the technology," says Mural. "What they can do isn't happening elsewhere."
Rodland says the task is daunting because the biomarkers are at very low concentrations and are hidden in the noise of thousands of proteins. Smith adds that PNNL's methods and instruments can identify many more proteins and allow samples from more patients to be analyzed than other labs.
After identifying proteins that might qualify as biomarkers, the researchers will scour the blood samples to determine whether the proteins are there as well as in the tissue, and ensure that the proteins only show up in the blood samples of women who had aggressive cancer. At the end of two years, the researchers expect to have a handful of biomarkers that can then be tested in women newly diagnosed with breast cancer.
|Contact: Mary Beckman|
DOE/Pacific Northwest National Laboratory