|February 09, 2009|
|Scientists at the University of North Carolina at Chapel Hill have developed a new genomic test designed to help clinicians predict which breast cancer patients are most likely to survive the disease and which treatments may be most effective in increasing those chances of survival.
J.S. Marron, PhD, Amos Hawley Distinguished Professor of Biostatistics in the UNC Gillings School of Global Public Health, contributed to the study.
By specifically measuring the activity level of a small subset of the 20,000 plus genes that may be “turned on” or “turned off” within each tumor, the test can give patients a more accurate picture of how their disease might progress, researchers say.
Designed by a multi-institutional team of scientists, the relatively simple test was specifically designed to be performed using equipment present in many hospital laboratories, an advantage over other recently developed genomic tests that require more sophisticated technology and expertise.
“Here we have developed a method that can be used in the everyday clinic and has the potential to benefit all breast cancer patients,” said study co-author Charles Perou, PhD, associate professor of genetics and pathology in the UNC School of Medicine and a member of the UNC Lineberger Comprehensive Cancer Center. “Based on the genomics of a tumor, we can make good predictions about how a patient might do, but we can also define predictive markers that tell us which drugs to give patients.”
A report of the study appears in the Feb. 9 (Monday) online issue of the Journal of Clinical Oncology.
One in eight women in the United States will receive a diagnosis of breast cancer in her lifetime. The disease occurs when mutations accumulate in critical genes — such as those that control cell growth and division or the repair of damaged DNA — allowing cells to grow and divide uncontrollably to form a tumor. The specific genetic changes in these tumor cells determine in large part how aggressively the cancer will behave.
A major focus of Perou’s research is to provide more biological information that can be mobilized in the fight against breast cancer. He and his colleagues used DNA microarrays or “gene chips” to scan the thousands of genes within tumor samples taken from breast cancer patients. They found that the samples could be classified into five biologic groups or subtypes – Luminal A, Luminal B, HER2-enriched, Basal-like and Normal-like – and that each group had a specific genomic signature corresponding to distinct disease outcomes. The researchers then honed in on a small subset of 50 genes that can still identify these biologic groups as robustly as the original list of thousands of genes.
In this study, Perou and his colleagues modified their approach to measure the activity levels of those 50 genes using a technology called RT-PCR. Then, using a separate set of 761 patients, they validated the test’s ability to predict patients’ actual outcomes. The researchers also showed – using another group of 133 patients – that the test was able to predict response to a common chemotherapy regimen. Clinical trials currently are being conducted to confirm the study’s results in even larger numbers of patients.
“Here we’ve demonstrated that this test can predict the likelihood a patient will relapse and can define the biologic subtype of their tumor – pieces of information that together could be used to make treatment decisions,” Perou said. “We also found that patients in just two groups actually benefited from the chemotherapy regimen we studied, whereas the patients in the other three groups showed a much lower response rate. The idea is for clinicians to use this knowledge to help determine what drugs a patient should get and should not get.”
The multi-center study was led by researchers at UNC’s Lineberger Comprehensive Cancer Center; the University of Utah Huntsman Cancer Institute, Salt Lake City; and Washington University Siteman Cancer Center, St. Louis, Mo.
Along with Perou, co-authors include Matthew Ellis, MD, associate professor of medicine, Washington University School of Medicine; and Philip S. Bernard, MD, assistant professor of pathology and medical director of Huntsman’s molecular pathology laboratory. Study co-authors from Perou’s laboratory at UNC include Joel S. Parker, the lead author and graduate student; Xiaping He, research associate; and Zhiyuan Hu, former postdoctoral fellow and current director of UNC pathology-genomics laboratory. UNC College of Arts and Sciences statistics professors Andrew B. Nobel, Ph.D., and J.S. Marron, Ph.D., who is also Amos Hawley Distinguished Professor of Biostatistics in the UNC Gillings School of Global Public Health, also contributed to the study. Laboratories at the University of Utah, the University of British Columbia and Washington University contributed to the study as well.
Perou is one of the inventors of the test and has patents pending for the technology described in this news release. Along with colleagues at the Huntsman Cancer Institute and Siteman Cancer Center, he is a partner in the company, University Genomics, which is working to commercialize the test.
The research was supported by the National Institutes of Health.