Seven researchers in the Fred Hutchinson/University of Washington Cancer Consortium have received grants from the Breast Cancer Research Foundation, or BCRF.
Their work will focus on almost every aspect of breast cancer: from its genetic drivers and potentially reducible risk factors, to treatment and survivorship, to new therapies and practices that could help those with metastatic, or stage 4, disease.
Fred Hutchinson Cancer Research Center scientists, who each received $175,000, include Senior Vice President and Clinical Research Division Director Dr. Nancy E. Davidson, holder of the Raisbeck Endowed Chair for Collaborative Research; cancer prevention researcher and author Dr. Anne McTiernan, and chemoprevention expert and translational researcher Dr. Thomas Kensler.
BCRF also awarded funds to University of Washington physician-scientists Dr. Julie Gralow, Dr. Nora Disis and Dr. Poorni Manohar as well as breast cancer geneticist Dr. Mary-Claire King. Gralow, Disis and King are faculty members in the Hutch’s Clinical Research Division. All are part of the Cancer Consortium’s Breast and Ovary Cancer Research Program.
Diet, exercise and gut microbiome
Davidson, a breast cancer researcher and medical oncologist at the Hutch’s clinical care partner Seattle Cancer Care Alliance, received funding to continue with the “Cook and Move for Your Life” randomized clinical trial, which is testing the effects of two different six-month diet and physical activity programs — one high-dose and one low-dose.
COVID-19 paused the trial and the researchers adjusted their interventions for a remote audience. They’ll now use web and text messaging platforms to communicate with participants, and all data collection will occur at home, including blood and stool collection.
In partnership with Hutch researcher Dr. Heather Greenlee, who directs the Integrative Medicine Program at SCCA, the trial seeks to test the effect of the intervention on changes in behavior as well as changes in biomarkers of inflammation in the blood. Data and biospecimens will be also used to measure the effects of diet and physical activity on the gut microbiota and bacteria metabolites that may be linked to breast cancer outcomes. The Hutch’s Dr. Neelendu Dey will lead the analyses on the effect of the intervention on the diversity and the abundance of gut microbial communities, their metabolites (e.g., short-chain fatty acids), and markers of systemic inflammation and gut barrier permeability, such as C-reactive protein and certain binding proteins.
Does physical activity prevent breast cancer?
Epidemiologist McTiernan will continue her research into the cancer prevention benefits of physical activity.
McTiernan’s ongoing ACE clinical trial is investigating the ACute Effects of Exercise in Women by examining blood and muscle tissue samples before and after 45 minutes of either exercise or rest. With the new BCRF funding, she and co-investigator Dr. Catherine Duggan, will use those biospecimens to look for breast cancer biomarkers related to inflammation and blood vessel growth and determine whether the effects of exercise are different in normal-weight women and obese or overweight women. The study, which is still recruiting, will also look at how exercise affects cell growth in a 3D model of breast tumor cells, and how exercise affects BRCA1 and p53 gene expression in lymphocytes, a type of white blood cell.
“If we find that acute exercise significantly alters these biomarkers,” she said, “it could help support guidelines for daily exercise for breast cancer prevention and could indicate that exercise, even without weight loss, is beneficial.”
Eating habits, estrogen and breast density
Translational cancer prevention researcher Kensler will continue his work examining the impact of diet on breast cancer risk. In a collaboration with epidemiologist Dr. Holly Harris, Kensler will examine whether a diet associated with estrogen levels is associated with breast cancer risk. He and his team will also assess breast density in younger women (under age 40), examining the influence of estrogen levels measured in the blood on breast density. And they will examine how breast density and body fat distribution are related, which may help us understand how body size impacts breast cancer risk. The study will also look at how diet earlier in a woman’s life impacts breast density.
“Our goal is to identify actionable ways that we can reduce breast cancer risk through dietary patterns,” he said, “and the identification of factors that influence breast density.”
Metastatic biopsies: are they being done?
Manohar, a health services researcher with the Hutchinson Institute for Cancer Outcomes Research and a breast oncologist at SCCA, will study the real-world use of biopsy in metastatic breast cancer recurrence to make sure these patients are receiving the appropriate treatment. She wants to determine if second biopsies are being performed when patients recur.
“In early breast cancer, hormone status is a defining factor in choosing therapy,” she said. “But when there’s a metastatic recurrence, national guidelines call for another biopsy. This is because 20-30% of the time there’s a mismatch in hormone status between early and advanced, or metastatic cancer.”
Clinicians who rely on the original biopsy or pathology report to select treatment for a new metastatic tumor, she said, could hit the cancer with the wrong targeted treatment unless they re-biopsy.
Bone mets, immunotherapy and more
Hutch / UW / SCCA physician-scientist Gralow will continue her research into bone metastasis and how bisphosphonates can be used to reduce the risk of bone metastasis and death. Gralow will continue to identify which patients are at risk for developing bone mets and which might benefit by receiving a bisphosphonate agent. She and her team are also studying the long-term effects of these drugs, including the incidence of fractures and dental problems.
Disis, a professor of medicine at the UW and a Hutch clinical researcher, will continue her work in metastatic breast cancer, particularly the triple-negative subtype. Disis has developed a new vaccine that targets breast cancer stem cells — the cells responsible for drug resistance and metastasis. In a Phase I clinical trial, the vaccine elicited a robust immune response. In mouse models of breast cancer, the vaccine shut down tumor promoting pathways, re-sensitizing the tumor to chemotherapy. (TNBCs rapidly develop drug resistance). With this new grant, Disis will prepare for a Phase II clinical trial for the vaccine, STEMVAC, by testing whether immunizing animals with triple-negative breast cancer with STEMVAC at the same time as they receive chemotherapy will be more effective than chemotherapy alone. The results will be the basis of a clinical trial in patients with metastatic TNBC to determine if the vaccination with chemotherapy can inhibit the development of drug resistance.
Lasker Award winner King will continue to lead the New York Breast Cancer Study which aims to identify all the genes responsible for inherited breast cancer among women of Ashkenazi Jewish ancestry. So far, King has identified several genetic causes of breast cancer beyond BRCA gene mutations in these women. With this new funding, she hopes to identify, through new technology, small structural deletions in DNA that previously have been undetectable.
The Breast Cancer Research Foundation, 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 and Ovary Cancer Research Program.
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Breast cancer researchers from Hutch / UW Cancer Consortium gain BCRF funding - Fred Hutch News Service
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