“Those of us involved in global health realize our commonality as people on this earth,” said Jeffrey Weitzel, M.D., Dr. Norman & Melinda Payson Professor in Medical Oncology and director of the Division of Clinical Cancer Genomics in the Department of Population Sciences at City of Hope. “We’re all brothers and sisters. We don’t want anybody to be left out given that preventive care can spare lives and lessen the burden of cancer. Our goal is to address disparities globally.”
A leading genetics researcher and physician scientist focused on breast cancer risk assessment and prevention, Weitzel has been at the forefront of developing low-cost genetic screening in Central and South American populations. He’s currently working with Gad Rennert, M.D., Ph.D., Director of Clalit National Israeli Cancer Control Center at Carmel Medical Center in Haifa, Israel, on an important study to search for genetic mutations that increase the risk of breast cancer among Israeli women. Ultimately, the scientists hope to better identify a wider swath of women who need early cancer screening and to develop more inclusive and cost-effective approaches to risk assessment in underserved communities around the world.
Weitzel and Rennert’s collaboration is the result of a grant from the Jacki and Bruce Barron Cancer Research Scholars’ Program, which was established in 2016 by a gift from the Harvey L. Miller Family Foundation to support the exchange of ideas, strategies and therapies between City of Hope and Israeli investigators backed by the Israel Cancer Research Fund.
“I’ve known Gaddi for years,” said Weitzel, who joined City of Hope in 1996. “This is a collaboration born of friendship. We were colleagues for some time but never had the modus and the opportunity to formally work together on a project, so this grant catalyzed a scientific collaboration.”
In the general population, women who get breast cancer are typically diagnosed in their sixties, but those with a genetic version of the disease tend to present with it at a much younger age. Scientists already know that inherited genetic mutations account for 5 to 10% of breast cancers, but most cancer screening focuses on the well-known BRCA1 and BRCA2 genes, and often only on the few recurrent (founder) mutations that are prevalent in Jewish populations. Weitzel and Rennert are investigating other genetic mutations to determine which are associated with increased risk of breast cancer in young women who do not have one of the founder BRCA mutations.
The pair’s current broader study of breast cancer susceptibility mutations is a continuation of a Barron-funded project they embarked upon in the program’s inaugural year that focused specifically on a search for germline mutations of the TP53 tumor-suppressor gene in Israeli breast cancer patients under the age of 35. Younger women with breast cancer who do not have a BRCA mutation not infrequently show a TP53 mutation as the cause. “We chose that gene first,” Weitzel said, “because it had been completely unstudied and it was responsible, at least in the European-based populations that we dealt with, for up to 7% of these women.”
As their partnership gained momentum, Weitzel and Rennert visited each other’s labs, leveraged events they were both attending to make time for project meetings and worked out the logistical kinks of the cross-Atlantic collaboration, which occasionally involved mollifying a suspicious New York Customs office that had confiscated samples. Though they did not find any inherited TP53 mutations in a small pilot sample set, they did identify other clinically actionable gene mutations that increase breast cancer risk. Rennert is now going back to share those results with Israeli families in his original registry to try and identify which of the women who did not have breast cancer may still be of concern because of these other mutations. “So the first phase of the project is already yielding changes in clinical care at the family level in Israel,” said Weitzel.
For their current study, Weitzel and Rennert have widened their scope to include women up to the age of 45 as they look for new gene variant patterns in those who are clinically most appropriate and most in need. To do this, they are comparing patient samples from an Israeli study with samples in City of Hope’s Clinical Cancer Genomics Community Research Network to identify recurring mutations relevant to a patient’s ethnicity or ancestral background.
Ultimately, they plan to create a risk scale based on the type of mutation a high-risk patient has, as well as to document and characterize these patterns so they can change policies and approaches to testing in Israel. Weitzel and Rennert hope to provide Israeli geneticists with a wider, more economical spate of tools that will allow them to be more inclusive in their studies.
“We want to reach the maximum number of people with an effective approach,” Weitzel said. “Our interest is in people getting the best care. I’m interested in expanding access to every possible population, because the potential for prevention is so real.”
As a bonus, Weitzel and Rennert can align their results with a huge breast cancer study already taking place in the U.S. “So there are other ways that this data, beyond going straight back to take care of patients, is going to be used to help collaborate in a broader sense at another level so we are able to understand how it compares with other world populations,” Weitzel said.
Weitzel considers this sort of international collaboration essential to enhancing doctors’ ability to treat a much broader portion of the world’s population. “When I look at the breadth of the science in the Barron program, it’s breathtaking,” he said. “Of all the Barron projects, we’re probably the closest to the bedside, and it’s hard to get that kind of thing funded because it’s like, ‘Oh, of course we should be doing comprehensive testing.’ But because that’s an obvious answer, [potential benefactors] don’t see the need for money.”
“Without this grant, Gaddi and I wouldn’t have been able to catalyze our collaboration,” Weitzel added. “We’re motivated clinician scientists from different sides of the Atlantic with different facets of expertise. So as we continue to dive deep, catalyzed by the Barron program support, we’re contributing to science, but in the meantime we’re making a difference in families today.”