A set of 50 genes can be used to reliably identify the four known types of breast cancer, according to research conducted at Washington University School of Medicine in St. Louis and collaborating institutions.
Using this 50-gene set, oncologists can potentially predict the most effective therapy for each breast tumor type and thereby personalize breast cancer treatment for all patients.
"Unlike a widely used genomic test that applies only to lymph-node negative, estrogen-receptor positive breast cancer, this new genomic test is broadly applicable for all women diagnosed with breast cancer," says breast cancer specialist Matthew Ellis, M.D., Ph.D., a member of the Siteman Cancer Center at Barnes-Jewish Hospital and Washington University.
The study was reported Feb. 9, 2009, through advance online publication in the Journal of Clinical Oncology . Ellis' collaborators include co-authors Charles Perou, Ph.D., associate professor of genetics and pathology at the University of North Carolina at Chapel Hill School of Medicine, Philip S. Bernard, M.D., assistant professor of pathology and medical director of the molecular pathology laboratory at the University of Utah Huntsman Cancer Institute, and Torsten Nielsen, M.D., Ph.D., assistant professor of pathology and laboratory medicine at the University of British Columbia.
Breast cancer results from genetic abnormalities in breast tissue, but not all breast cancers have identical genetic alterations. Ellis and his colleagues analyzed the gene activity of more than 1,000 breast tumors to identify and validate the genetic signature of each of the four types of breast cancer. Although the cancer types are distinguished by thousands of genetic differences, the researchers were able to narrow the list down to a set of 50 of these genes that could uniquely identify each type.
These tumor types have been previously defined and are known as luminal A, luminal B, HER2-enriched and basal-like. The latter three types are generally considered types with a poor prognosis. Another genomic test commonly used in clinical practice, OncotypeDX, does not identify all four tumor types.
"Our test is the first to incorporate a molecular profile for the basal-like type breast cancers," says Ellis, professor of medicine in the Division of Medical Oncology at Washington University School of Medicine. "That's important because these breast cancers are arguably the most aggressive yet the most sensitive to chemotherapy. By identifying them we can ensure they are treated adequately."
Breast cancer experts typically also identify a fifth breast cancer type known as normal-like. The 50-gene set also recognizes the normal-like type. But the researchers found that instead of being a fifth type of breast cancer, the normal-like classification is an indicator that a sample contains insufficient tumor cells to make a molecular diagnosis and that a new sample needs to be taken.
In this study, the researchers also compared the activity of the 50-gene set to how well 133 breast cancer patients responded to standard chemotherapy. They found that their genetic test was highly sensitive and very predictive for chemotherapy response. The test was more predictive than typically used clinical molecular markers such as estrogen receptor status, progesterone receptor status or HER2 gene expression status.