The Fred Hutchinson Cancer Research Center in Seattle will oversee two major grants totaling nearly $8 million to develop a blood test that can be used in conjunction with mammography to improve early detection of breast cancer.
The first, a $7 million, four-year Breast Cancer Center of Excellence grant to Fred Hutchinson from the U.S. Department of Defense, will involve investigators from 10 institutions in Seattle, Houston and Los Angeles.
The second is a grant of nearly $1 million from a unique, multi-year, public-private partnership of the Avon Foundation and the National Cancer Institute called "Progress for Patients." The funds will be split equally among Fred Hutchinson, the University of Alabama, Fox Chase Cancer Center and M.D. Anderson Cancer Center.
Nicole Urban, Sc.D., a member of Fred Hutchinson's Public Health Sciences Division, will serve as principal investigator of both initiatives.
"Our goal for both projects is to evaluate a variety of breast-cancer biomarkers for their contribution to the early detection of breast cancer. Our vision is that a simple blood test could be used along with mammography to detect breast cancer early in the disease process. We are particularly interested in markers that identify aggressive forms of breast cancer that are missed by mammography," said Urban.
While mammography indeed saves lives - reducing deaths from breast cancer by up to 30 percent among women over age 50 - it misses about one in five breast cancers overall. Mammography is least effective in detecting cancer in younger women, who tend to have dense breast tissue that is difficult to X-ray. Other limitations of mammography in younger women include a high rate of false positives that result in unnecessary biopsies and the inability to distinguish between aggressive, life-threatening cancers versus slow-growing tumors that may not need treatment.
The central focus of the DoD project, called the Center for the Evaluation of Biomarkers for Early Detection of Breast Cancer, will be to develop and test a panel of serum biomarkers - substances in the blood, such as proteins, or specific genetic sequences - which are detected in higher-than-normal amounts in women with breast cancer. Blood and tissue samples will be obtained from 1,800 women undergoing mammography, biopsy or breast-cancer surgery during the next four years at two clinical sites: Swedish Medical Center in Seattle and Cedars-Sinai Medical Center in Los Angeles.
Biomarkers to be evaluated will include:
- Circulating breast-tumor cells, which can be identified by the fact that they contain specific genetic instructions for making proteins associated with breast tissue, such as the protein mammaglobin;
- Growth factors detectable in serum or plasma that are associated with angiogenesis, or blood-vessel development, often present in cancer because tumors need a blood supply to survive. Growth factors to be evaluated include vascular endothelial growth factor, or VEGF, which is associated with 80 percent of breast tumors and is an indicator of poor prognosis among women with estrogen-sensitive tumors;
- Lipid markers, or fatty acids, detectable in serum or plasma, which are associated with pathways of cancer development. Preliminary studies with various lipid markers have resulted in breast-cancer detection rates of up to 90 percent with a "false-positive" rate of only 5 percent;
- Antibodies to mutated or over-expressed proteins that are associated with aggressive breast cancer, such as Her2/neu and p53, which are found in 30 percent and 50 percent of breast tumors, respectively; and
- Other promising new markers that may become available from emerging new technologies such as proteomics, which can identify telltale "protein signatures" in the blood that are linked to diseases such as cancer.
Using biomarkers for cancer screening is not new; single-marker blood tests for prostate and ovarian cancer, for example, have been used widely for more than a decade. An enzyme called PSA, or prostate-specific antigen, is used to detect prostate cancer while it is still localized and treatable, while a protein called CA-125 can flag the recurrence of ovarian cancer. Studies are under way to test the effectiveness of CA-125 in detecting early-stage disease in asymptomatic women. However, no adequate breast-cancer biomarker has yet been identified, perhaps because there is no single pathway to breast-cancer development, Urban said.
"It is unlikely that we will ever find a single marker that will work perfectly to detect and diagnose breast cancer, because breast cancer is not one disease; not all breast cancers look the same at the molecular level," she said. "We challenge the paradigm that a single marker that detects all breast cancer is even necessary. Instead, we will seek a panel of about 10 synergistic markers that can be used in concert with each other."
There are several ways a breast-cancer biomarker panel could be used, Urban said. For example, a woman could have her blood tested in conjunction with her annual screening mammogram. If the mammogram were clearly positive, she would be referred for biopsy. If the mammogram findings were ambiguous, she would be referred for biopsy only if the marker panel suggested a malignancy. If the mammogram were negative but the blood test suggested cancer, she would be referred for additional tests such as MRI, or magnetic-resonance imaging. Such a marker panel also could be used between annual mammograms to find fast-growing cancers at an earlier stage than they would otherwise be identified, especially in high-risk women.
SOURCE:
Fred Hutchinson Cancer Research Center (http://www.fhcrc.org)
