"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.
They found that luminal A was not sensitive to the chemotherapy, suggesting that patients with this good-prognosis type can forgo chemotherapy in favor of hormone-based therapy. They showed that among the poor-prognosis tumor types, basal-like breast cancer was the most sensitive to the chemotherapy and luminal B the least.
"Luminal B tumors are a very poor prognosis group, and none of the current conventional therapies are particularly effective against it," Ellis says. "The ability to identify luminal B tumors accurately makes it possible to develop better therapies for this type."
Ellis says more than 20 drugs are available to treat breast cancer. The researchers are now investigating how each tumor type responds to these drugs to help determine the best treatment for each. Their 50-gene set can be assayed in preserved tumor samples left over from standard diagnostic procedures, so the group plans to study tumor samples from breast cancer cases going back a decade or more. Since the patients in these cases have already been treated, the researchers can relatively quickly discover how well various therapies worked for each breast cancer type.
The genomic test technology is patented and will be distributed through University Genomics, a company co-owned by Washington University, the University of Utah and the University of North Carolina. This year University Genomics is working with Associated Regional and University Pathologists Inc., a reference laboratory at the University of Utah, to provide a site where the 50-gene test will be available. Ellis is one of the inventors of the test and holds patents for the technology described in this news release.
Parker JS, Mullins M, Cheang MCU, Leung S, Voduc D, Vickery T, Davies S, Fauron C, He X, Hu Z, Quackenbush JF, Stijleman IJ, Palazzo J, Marron JS, Nobel AB, Mardis E, Nielsen TO, Ellis MJ, Perou CM, Bernard PS. Supervised risk predictor of breast cancer based on intrinsic subtypes. Journal of Clinical Oncology. Feb. 9, 2009 (advance online publication).
Funding from the National Cancer Institute, the Breast Cancer Research Foundation, the Susan G. Komen Foundation, the Huntsman Cancer Institute Foundation and the ARUP Institute for Clinical and Experimental Pathology supported this research.
Washington University School of Medicine's 2,100 employed and volunteer faculty physicians also are the medical staff of Barnes-Jewish and St. Louis Children's hospitals. The School of Medicine is one of the leading medical research, teaching and patient care institutions in the nation, currently ranked third in the nation by U.S. News & World Report. Through its affiliations with Barnes-Jewish and St. Louis Children's hospitals, the School of Medicine is linked to BJC HealthCare.
Siteman Cancer Center is the only federally designated Comprehensive Cancer Center within a 240-mile radius of St. Louis. Siteman Cancer Center is composed of the combined cancer research and treatment programs of Barnes-Jewish Hospital and Washington University School of Medicine. Siteman has satellite locations in West County and St. Peters, in addition to its full-service facility at Washington University Medical Center on South Kingshighway.
Gwen Ericson | EurekAlert!
Further reports about: > 50-gene set > Cancer > Genetic differences > HER2-enriched tumors > New genomic test > Oncology > breast cancer > breast cancer treatment > breast tissue > estrogen-receptor positive breast cancer > gene activity > genetic abnormalities > luminal A > luminal B > lymph-node negative breast cancer > molecular pathology
Scientists uncover the role of a protein in production & survival of myelin-forming cells
19.07.2018 | Advanced Science Research Center, GC/CUNY
NYSCF researchers develop novel bioengineering technique for personalized bone grafts
18.07.2018 | New York Stem Cell Foundation
A new manufacturing technique uses a process similar to newspaper printing to form smoother and more flexible metals for making ultrafast electronic devices.
The low-cost process, developed by Purdue University researchers, combines tools already used in industry for manufacturing metals on a large scale, but uses...
For the first time ever, scientists have determined the cosmic origin of highest-energy neutrinos. A research group led by IceCube scientist Elisa Resconi, spokesperson of the Collaborative Research Center SFB1258 at the Technical University of Munich (TUM), provides an important piece of evidence that the particles detected by the IceCube neutrino telescope at the South Pole originate from a galaxy four billion light-years away from Earth.
To rule out other origins with certainty, the team led by neutrino physicist Elisa Resconi from the Technical University of Munich and multi-wavelength...
For the first time a team of researchers have discovered two different phases of magnetic skyrmions in a single material. Physicists of the Technical Universities of Munich and Dresden and the University of Cologne can now better study and understand the properties of these magnetic structures, which are important for both basic research and applications.
Whirlpools are an everyday experience in a bath tub: When the water is drained a circular vortex is formed. Typically, such whirls are rather stable. Similar...
Physicists working with Roland Wester at the University of Innsbruck have investigated if and how chemical reactions can be influenced by targeted vibrational excitation of the reactants. They were able to demonstrate that excitation with a laser beam does not affect the efficiency of a chemical exchange reaction and that the excited molecular group acts only as a spectator in the reaction.
A frequently used reaction in organic chemistry is nucleophilic substitution. It plays, for example, an important role in in the synthesis of new chemical...
Optical spectroscopy allows investigating the energy structure and dynamic properties of complex quantum systems. Researchers from the University of Würzburg present two new approaches of coherent two-dimensional spectroscopy.
"Put an excitation into the system and observe how it evolves." According to physicist Professor Tobias Brixner, this is the credo of optical spectroscopy....
13.07.2018 | Event News
12.07.2018 | Event News
03.07.2018 | Event News
20.07.2018 | Power and Electrical Engineering
20.07.2018 | Information Technology
20.07.2018 | Materials Sciences