The National Cancer Institute has awarded $11.5 million to Fred Hutchinson Cancer Research Center to lead a five-year, Seattle-based breast cancer research consortium. The goal of the endeavor is to positively impact breast cancer prevention, detection, treatment and care of women who have or are at risk for the disease.
Known as the Seattle Cancer Consortium Breast SPORE (Specialized Program in Research Excellence), the initiative will involve 25 investigators at the Hutchinson Center and the University of Washington as well as project consultants from a variety of institutions in the U.S. and abroad.
Co-principal investigators Peggy L. Porter, M.D., and Martin (Mac) Cheever, M.D., members of the Hutchinson Center's divisions of Human Biology and Clinical Research, respectively, will lead the consortium.
"The collaborations that were formed between basic, clinical and translational scientists as part of the Hutchinson Center/University of Washington Cancer Consortium were key to the success of the breast cancer SPORE funding," said Porter, also a professor of pathology at the UW School of Medicine.
Developing targeted breast cancer treatments is the unifying mission behind the consortium's four scientific projects. Cancers are highly individual from a genetic and molecular perspective and they respond best to therapies aimed at specific mechanisms of cancer development. Because targeted therapies interfere with specific molecules involved in tumor growth, they often have less severe side effects than standard chemotherapy and radiation, which treat the cancer but damage healthy tissue.
"Our mission is to provide unique breast cancer treatment options that are developed from the science at the Hutchinson Center and the UW," said Cheever, who is also a professor of medicine and associate director of medical oncology at UW. He is an expert in cancer immunotherapy who is working to move cutting-edge science out of the lab and into the clinic, where it will be made available to cancer patients enrolled in clinical studies, a process known as translational research.
Below are brief descriptions of each project.
Project 1: Predicting mortality and response to therapy - Aggressive breast tumors often express abnormally low amounts of a cell cycle inhibitor called p27. Low levels of p27 are often a marker of poor outcome in breast cancer. This project will follow a small number of breast cancer patients who have survived at least five years to test the possibility that p27 expression in tumor cells predicts poor prognosis or poor response to anti-estrogen and/or anti-HER2 therapies. If this holds true, it will be possible to develop a test that will not only predict which women will fail treatment, but also will allow researchers new insight into which targeted therapies are needed to treat drug-resistant tumors. Project co-leaders: SPORE co-principal investigator Porter will lead this project along with James Roberts, M.D., Ph.D., a member of the Basic Sciences Division at the Hutchinson Center.
Project 2: Targeted T-cell immunotherapy of breast cancer - This project will evaluate new immunotherapeutic approaches for breast cancer in a phase 1 clinical trial in which cells of the immune system will be isolated and programmed to target and kill breast cancer cells and then transferred back to the patient. The results of this research, which aims to kill cancer without harming healthy tissue, will provide insights into the potential utility of adoptive T-cell therapy for breast cancer, as well as the broader application of this approach for the treatment of other solid tumors. Project co-leaders: Stanley Riddell, M.D., a member of the Hutchinson Center's Clinical Research Division; and Lupe Salazar, M.D., an assistant professor of medicine in the Department of Oncology at the University of Washington School of Medicine.
Project 3: Predicting poor prognosis and poor response to systemic therapy - Using PET and MRI imaging to measure glucose metabolism and blood flow, respectively, in patients with locally advanced breast tumors, Hutchinson Center researchers have identified a "metabolic signature" indicative of breast cancers that become resistant to systemic chemotherapy, which increases the likelihood of early relapse and death. This project aims to better understand the underlying biology of drug-resistant tumors and develop treatments that overcome drug resistance. By using imaging technologies to identify drug-resistant tumors, such patients can be directed toward therapy that is more likely to work in the long term. Project co-leaders: David Hockenberry, M.D., a member of the Clinical Research Division at the Hutchinson Center; and David Mankoff, M.D., professor of radiology at UW School of Medicine.
Project 4: Identifying genetic biomarkers that could prevent over- or under-treatment in women with breast cancer - The goal of this project is to identify markers of DNA damage repair as a way to predict outcome in breast cancer and prevent over- or under-treatment of the disease. Candidate biomarkers will be identified from tissue samples taken from a population-based group of approximately 2,000 survivors of invasive breast cancer who are being followed for recurrence and mortality. By identifying such markers, researchers hope to improve treatment decision-making. Project leader: Amanda Paulovich, M.D., Ph.D., an associate member of the Hutchinson Center's Clinical Research Division; project co-leader: Kathleen Malone, Ph.D., a member of the Hutchinson Center's Public Health Sciences Division.
Established by Congress in 1992, the SPORE program was created to promote collaboration between basic and applied scientists to speed the testing of new approaches to the prevention, early detection, diagnosis and treatment of a variety of cancers. The Hutchinson Center also leads SPORE initiatives in prostate and ovarian cancer research.
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