Breast cancer may be several diseases

$8.5 million study seeks best therapy for each

Physicians have come to understand that what we call breast cancer is really several — probably at least five — different diseases that need different treatments and have different outcomes. Now researchers at Washington University School of Medicine in St. Louis and collaborating institutions in the United States and Canada plan to evaluate these breast cancer subtypes and determine the likely prognosis and most effective treatment for each.

The group is headed by Matthew J. Ellis, M.D., Ph.D., the Anheuser-Busch Endowed Professor in Medical Oncology, and funded by a new $8.5 million, five-year grant from the National Cancer Institute (NCI).

“We’re working to develop a new diagnostic and treatment paradigm,” says Ellis, a breast-cancer specialist with the Siteman Cancer Center at Washington University School of Medicine and Barnes-Jewish Hospital. “We’re analyzing the genes active in breast tumors to characterize the biological behaviors of each breast-cancer subtype. This will enable us to more effectively classify breast tumors and then to work to optimize treatment protocols based on this information.”

Older methods of determining breast cancer treatment relied mainly on tumor location, size and spread. The rise of genetic analyses uncovered genetic indicators, such as overexpression of the HER2 gene in some breast cancers, that may lead to treatment with specifically targeted drugs.

But scientists recognize that cancer is a complex disease that accumulates many, perhaps thousands of genetic abnormalities. So researchers like Ellis have begun using tools that can simultaneously measure the activity of many genes to look for larger patterns of gene activity associated with a particular cancer.

“In a sense, we are looking for the genetic signatures of each breast cancer subtype,” Ellis says. “Previous research has shown that you can delineate categories of breast tumors based on their genetic signatures. But right now the categories are a little like rough estimates, because there is ambiguity about which genes should be considered markers for each cancer subtype.”

Scientists have outlined five categories of breast tumors referred to as Luminal A and B, Normal Breast-like, HER2-positive and Basal-like, but the profile of gene activity that uniquely characterizes each has not been thoroughly settled.

With the new grant, which originates from the NCI’s Specialized Program for the Evaluation of Cancer Signatures (SPECS), Ellis’s group will analyze gene expression in breast tumor tissues that have been banked from patients diagnosed 10 to 15 years ago. They will test the activity of a set of 100 carefully selected genes in each tumor, and this “cold case” detective work should allow them to definitively assign genetic signatures to the established breast tumor categories.

Moreover, because the patients in the study have already undergone treatment and extensive follow-up, the researchers can compare their breast-cancer categories to each patient’s treatment protocol to quickly resolve the question of which therapies work best for each cancer subtype.

“Our long-term goal is to develop a broadly applicable subtyping test for all patients with early-stage breast cancer,” Ellis says. “This should lead to highly effective, personalized treatments that improve outcomes for breast cancer patients.”

The research project is a collaboration among Washington University School of Medicine, the University of North Carolina-Chapel Hill, the University of Utah Huntsman Cancer Center, the University of British Columbia and the Cancer and Leukemia Group B—a network of university medical centers, community hospitals and oncology specialists.

Washington University School of Medicine’s full-time 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 NCI-designated Comprehensive Cancer Center within a 200-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.