Photo by Clay Eals
Much as the war against terrorism en meshes ground troops, intelligence efforts and technology, a winning fight against breast cancer requires a combination of warriors, spies and tools.
The effort to head off this biological enemy, which strikes about 200,000 American women each year, relies on surgical strikes and drugs, epidemiological and molecular surveillance for risk factors and cancer genes, and an evolving armament of tools for prevention, screening, early disease detection and effective treatment.
All these tactics are used by the scientists in the Breast Cancer Research Program, who recognize that no single avenue of investigation will yield the best cures and prevention schemes for a disease expected to claim 40,000 lives in the United States this year.
Members of this diverse group of breast-cancer experts - including epidemiologists, oncologists, surgeons, geneticists, pathologists and other specialists from local institutions - have merged their talents to battle clinically important research problems in breast cancer.
The goal, said Dr. Peggy Porter, head of the program and an investigator in the Human Biology and Public Health Sciences divisions, is to continue the strong breast-cancer research at the participating institutions and build leading-edge collaborations in what is known as translational research.
"Our emphasis, and the emphasis in the field, is to maximize the exchange of laboratory discoveries and observations made in the clinic and in the population to improve clinical outcomes from breast cancer," she said.
"The opportunities to do this now are tremendous, as we have forged close ties with the Seattle Cancer Care Alliance, the University of Washington Academic Medical Center and the Center for Health Studies at Group Health Cooperative."
The Alliance outpatient clinic's location on the Day Campus, along with enhanced collaboration with the UW and other local institutions, make possible one of Fred Hutchinson's primary goals - to build research programs into breast cancer and other solid tumors whose stature matches the stellar reputation of the center's longstanding leadership in leukemia research and treatment.
Avon Foundation gift for new initiatives
The Breast Cancer Research Program, Porter said, has a well-established reputation for accomplishments in understanding environmental and genetic risk factors for breast cancer and for leading studies in breast-cancer prevention through diet, exercise and risk-reducing drugs.
New initiatives to involve scientists from all four divisions seek to increase research into cancer prevention, detection, and treatment. These efforts received a significant boost last year by a $2.5 million gift from the Avon Foundation.
Porter said the Avon funds support research in immunotherapy for breast cancer (a strategy to harness the power of the immune system to fight disease), innovative pilot projects in all areas of breast-cancer research and new breast imaging and screening strategies.
"Enormous progress has been made in using immunotherapy to treat cancers and diseases that affect the blood and immune system," she said, citing research by Clinical Research Division investigators. "We hope to take advantage of these findings to see whether similar strategies can be used against breast cancer."
The Avon gift also supports an important new collaboration with Harborview Medical Center that addresses the needs of underserved women with breast disease. Drs. Joann Elmore and Hannah Linden, physicians at Harborview, already have used funds to start an Avon Safety Net fund to pay for tests not covered by insurance as well as transportation, child care and hospice, when needed.
The Avon funds have helped to establish at Harborview a regional site for the Centers for Disease Control's Breast and Cervical Health Care program, which will provide previously unavailable breast and cervical cancer screening for low-income women.
The collaboration will help insure that advances in breast-cancer prevention, early detection, and treatment are available to women, regardless of their income and insurance status.
Basic research, clinical advances
Translational research encompasses a broad spectrum of research, including drug development and the identification of molecular signposts known as markers, that may reveal the earliest onset of cancer or offer insight into the best treatment strategy for a particular type of tumor.
Potential targets for drug development include molecules that regulate the cell cycle, a process that is disrupted in tumor cells. Such chemotherapeutic agents could emerge from interdisciplinary collaborations among Dr. Robert Livingston, a UW oncologist, Dr. Jim Roberts, a cell-cycle expert in the Basic Sciences Division, Dr. Julian Simon, a chemist in the Clinical Research and Human Biology divisions, and Porter, a pathologist.
Funding from the Breast Cancer Research Foundation to Porter and Livingston is supporting the construction and testing of tissue microarrays, which will be used to identify cell-cycle abnormalities that predict response to particular therapies.
With Porter, Drs. Janet Daling and Kathi Malone, epidemiologists in PHS, are particularly interested in identifying patient characteristics and new tumor markers that distinguish types of breast tumors, predict clinical outcome and let physicians tailor treatment to individuals.
The hunt for useful markers requires access to breast-tumor tissue samples.
Using Avon foundation funds to support database development and tissue collection, Porter and UW breast surgeons Drs. Ben Anderson, Gary Mann, Ray Yeung and Roger Moe, and Polyclinic breast surgeons Drs. Rick Clarfeld and Kristi Harrington, have established a breast-specimen repository that will make much-needed tissue and blood samples accessible to breast-cancer researchers.
Translational research goes beyond the laboratory, and the program's strength in cancer prevention and epidemiology continues to be an important part of the approach.
Epidemiologic studies provide clues to genetic and environmental risk factors that may translate into indicators of high risk or become the foundation for interventions to reduce risk, while prevention research tests potential interventions for their ability to reduce cancer risk.
Two studies conducted at the center exemplify the power of large cohorts to help define strategies for risk reduction.
A team of PHS investigators consisting of Drs. Ross Prentice, division director, and Garnet Anderson, Andrea LaCroix, Ruth Patterson and Shirley Beresford lead the center's program in the multi-site Women's Health Initiative.
The WHI is a randomized clinical trial involving more than 67,000 women that evaluates breast-cancer incidence and other outcomes related to low-fat eating patterns, hormone-replacement therapy, and calcium and vitamin D supplementation.
Dr. Emily White, a PHS and UW epidemiologist, leads the Vitamins and Lifestyle Study, designed to investigate the association of supplemental vitamin C, vitamin E, calcium and multivitamin intake with total incidence of breast, lung, prostate and large-bowel cancers. These studies will provide data to understand the role that diet and vitamin supplements play in breast-cancer risk.
Inner workings of the program
The development of the program's infrastructure, a priority for Porter, has received strong institutional support from the center.
Porter led a group of basic and clinical breast researchers in a recent application for funding from the National Cancer Institute to establish a Specialized Program of Research Excellence (SPORE) in Breast Cancer.
"Coming together for the SPORE application was extremely useful for forming new collaborations that will enhance the program objectives and lead to future projects," she said. "We are in an excellent position to attract new investigators in breast-cancer research over the next few years and, as a group, to have a major impact on this disease."
Avon awards four grants for breast-cancer pilot projects
The Avon Foundation's Pilot Project Fund has awarded grants for four projects totaling $120,000 in its first round of applications.
The fund's goal is to provide support for developmental projects that focus on improving breast-cancer prevention, detection, diagnosis and/or treatment.
Criteria included an emphasis on interdisciplinary or translational research, an ability to attract scientists from other fields with innovative approaches to breast cancer, potential to improve services to vulnerable populations and potential for reducing incidence and mortality from breast cancer.
The four are:
- Identification of Genes that Regulate Cyclin E and p27, Dr. Bruce Clurman, Clinical Research and Human Biology divisions. This research aims to identify genes that regulate p27 and cyclin E, key components of the cell cycle, and to determine their relevance in cancer cells with abnormal cyclin E and p27 function.
- Studies of a Novel Bcl-xL Small Molecule Inhibitor in Animal Models of Breast Cancer, Dr. David Hockenbery, Clinical Research and Human Biology divisions. This pilot project will attempt to demonstrate activity of 2-MeAA in pre-clinical models of breast cancer. 2-MeAA is an inhibitor of Bcl-xL, a protein that blocks cell death that is frequently overproduced in cancer cells.
- Combined Oncolytic Adenoviral Therapy and Stimulation of an Anti-Tumor Immune Response, Dr. Andre Lieber, University of Washington. This project will investigate whether combining immuno-stimulatory mechanisms with cancer-fighting gene therapy enhances anti-tumor effects of the treatment.
- Mammographic Breast Density as a Noninvasive Surrogate Marker of Breast Epithelial Proliferative Activity in a Phytoestrogen Trial of Breast Cancer Survivors, Dr. Anne McTiernan, Public Health Sciences Division. This is an ancillary study for the UW/Seattle Cancer Care Alliance Phytoestrogen Trial, which studies the effect of a phytoestrogen intervention on normal breast tissue in postmenopausal breast-cancer patients. This study will measure mammographic density (using a specialized laser film digitizer) as a noninvasive marker for breast glandular proliferation.
Avon, breast-cancer program support immunotherapy
Dr. Nora Disis, an oncologist at the University of Washington, studies the immune response to HER2, an oncogene often overexpressed in breast-cancer.
She works to develop vaccines and effective immunologic treatments for breast and ovarian cancer. Through breast program initiatives, immunologists from the UW and Fred Hutchinson will join Disis to apply their expertise to immunotherapy strategies for breast cancer.
Dr. Stan Riddell in the Clinical Research Division, will welcome Dr. Wei Wang, a new Avon Fellow in Immunotherapy for Breast Cancer, into his lab in July.
A new proposal prepared by Riddell and Disis includes multiple approaches to immune modulation and projects from the labs of Drs. Thomas Spies and Cassian Yee from Clinical Research and Dr. Andre Leiber from the UW.
Studies on breast density, tamoxifen/raloxifene seek participants
Fred Hutchinson researchers seek healthy women to participate in a study to determine whether a medication gel applied to the breasts changes breast density thereby making it easier for doctors to interpret mammograms.
Participants will be randomly assigned to either a group that uses a gel containing 4-OHT (an investigational drug which is a derivative of tamoxifen) or a group that uses a placebo gel.
Both groups will apply the gel to their breasts once a day for six months.
Those eligible are premenopausal women between ages 18 and 45 who are not pregnant, breastfeeding or taking oral contraceptives. Participants also must have had a mammogram.
Participants will receive $150 for taking part in and completing the study.
The Breast Gel Study is funded by Besins International U.S. Inc.
The Study of Tamoxifen and Raloxifene (STAR), coordinated by the center-based Puget Sound Oncology Consortium, seeks women to participate in a study to prevent breast cancer.
To participate, women must be 35 years of age or older, have passed menopause and carry an increased breast-cancer risk based on age, family history and breast biopsy history.
Those deemed eligible to participate will be randomly assigned to take oral doses of tamoxifen or raloxifene daily for five years.
Twice a year, the women will undergo follow-up breast exams and health assessments, in addition to annual mammograms, pelvic exams and blood tests.
To learn more, call 206-667-6544.