Eight researchers in the Fred Hutchinson/University of Washington Cancer Consortium have received grants totaling nearly $2 million from the Breast Cancer Research Foundation, or BCRF, funding that will continue to fuel their research through 2019. Most of the grants will go toward new therapies for patients with metastatic cancers.
The grants were part of a record-breaking $63 million given out this year to mark BCRF’s 25 years of impact in the breast cancer research field.
Fred Hutchinson Cancer Research Center scientists, who each received at least $250,000, include Senior Vice President and Clinical Research Division Director Dr. Nancy E. Davidson, pathologist Dr. Peggy Porter, cancer prevention researcher Dr. Anne McTiernan, and chemoprevention expert Dr. Thomas Kensler. Translational researcher Dr. Cyrus Ghajar, who focuses on disseminated tumor cells and their role in metastatic breast cancer, will collaborate with Davidson on a newly funded project; he also received funds to continue a three-year research award initiated last year.
BCRF also awarded funds to University of Washington physician-scientists Dr. Julie Gralow and Dr. Nora Disis as well as renowned breast cancer geneticist Dr. Mary-Claire King. Gralow and Disis are both faculty members in the Hutch’s Clinical Research Division. All are part of the Cancer Consortium’s Breast Cancer Research Program.
Making tumor cells more sensitive to chemotherapy
Davidson will continue her work to develop ways to make dormant disseminated tumor cells, or DTCs, and micrometastases (tiny undetected metastatic sites) more susceptible to chemotherapies. “Successfully eliminating these precursors of metastases before they emerge would be game-changing,” she said, “potentially eliminating late recurrences altogether.” She will focus on powerful enzymes called kinases and how they influence treatment resistance, with an eye toward predicting which drug combinations bring about kinase inhibition and the eventual destruction of micromets and DTCs. She will collaborate with Hutch researchers Drs. Kevin Cheung, Cyrus Ghajar, and Taran Gujral. Davidson, who in 2017 received BCRF’s Jill Rose Award, is the president and executive director of Fred Hutch’s clinical care partner, Seattle Cancer Care Alliance, and she holds the Hutch’s Endowed Chair for Breast Cancer Research.
Assessing Chernobyl's impact on breast cancer
Porter will further explore the relationship between low-dose radiation exposure and breast cancer by looking at the molecular changes experienced by women exposed to radiation from the Chernobyl nuclear accident. She will conduct whole-genome sequencing (also known as next-gen sequencing) on both tumor and saliva samples gathered from Chernobyl women diagnosed with breast cancer. Porter will then compare the frequency of somatic genomic changes – that is, noninherited mutations caused by environmental exposures – between those exposed to the highest and the lowest cumulative radiation doses. Porter heads the Seattle Cancer Consortium Breast Cancer SPORE (Specialized Program of Research Excellence).
Studying the link between physical activity and breast cancer
Epidemiologist McTiernan will continue her research into the cancer prevention benefits of physical activity, collaborating with Hutch researchers Drs. Catherine Duggan, C.Y. Wang, Jean De Dieu Tapsoba and Gujral, as well as the Fred Hutch Prevention Center. Her study will use biological information and samples of blood and muscle tissue gathered from women who participate in either 45 minutes of exercise or 45 minutes of rest. Her analyses of their information and samples will determine the immediate effects of exercise on biomarkers (including insulin, glucose, and insulin resistance) of breast cancer risk. Her research will further determine whether the benefits of exercise are the same for overweight or obese women as they are for normal-weight participants and whether exercise’s effects on muscle tissue can explain associations between physical activity and breast cancer risk.
Connecting the dots between diet and breast cancer
Translational cancer prevention researcher Kensler, who recently joined the Hutch from the University of Pittsburgh, will work with Hutch epidemiologist Dr. Holly Harris to examine the impact of diet on breast cancer risk. His study will look at two regimens – an inflammation-associated diet and an anti-inflammatory diet – and measure their impact on inflammatory markers and breast density.
The study will also provide dietary counseling to study participants. “Our goal is to identify actionable ways that we can reduce breast cancer risk through healthy dietary changes,” he said.
Focusing on breast cancer metastasis
In addition to his collaboration with Davidson, Cheung and Gujral, translational researcher Ghajar will continue his focus on dormant DTCs and the microenvironment that allows these tumor cells to grow into metastasis. This research, conducted in collaboration with Dr. Mina Bissell of the Lawrence Berkeley National Laboratory and Dr. David Lyden of Weill Cornell Medicine, will target both early and late metastasis in dormant niches with three promising drugs.
Fred Hutch clinical researcher and SCCA breast cancer oncologist Gralow will continue her research into bone metastasis, often the first site of recurrence of metastatic breast cancer. Gralow is analyzing tissue, serum and blood samples from patients to identify specific markers that can determine which patients are at risk for developing bone mets and might benefit most from a class of drugs known as bisphosphonates. In clinical trials, these drugs have been shown to reduce bone loss and fracture, and improve symptoms in patients with bone mets.
UW’s Disis, a professor of medicine and director of its General Clinical Research Center, will continue her research in immunotherapy to benefit metastatic breast cancer patients. She is testing a new form of immune therapy in which immune cells called T cells are “supercharged” with immune-regulating proteins called cytokines, turning them into T-helper cells. Boosting the numbers of these cells, she believes, will help sensitize the breast cancer tumor cells to chemotherapy, killing the cancer and stabilizing disease in metastatic patients.
Identifying genes behind hereditary breast cancer
Lasker Special Achievement Award winner King is the first person to demonstrate that breast cancer can be inherited via mutations in the cancer-risk gene BRCA1. She will continue collaborating with researchers in the New York Breast Cancer Study and the Middle East Breast Cancer Study to identify all the genes responsible for inherited predispositions to breast cancer. King and colleagues aim to pinpoint breast cancer risk among women of Ashkenazi Jewish and Arab ancestry. King is the American Cancer Society Professor at UW.
The BCRF, founded in 1993 by Evelyn H. Lauder, is dedicated to “being the end of breast cancer” by advancing the world’s most promising research. BCRF-funded investigators have been deeply involved in breast cancer prevention, diagnosis, treatment and survivorship.
The organization has also been a generous longtime funder of the Fred Hutch/UW Cancer Consortium’s Breast Cancer Research Program.
