Experienced innovator’s technology reduces false-positive results from imaging
With plenty of innovations under his belt, David Walt, PhD, is not one to sit on his laurels. One of his latest innovations stems from the dreaded diagnoses of breast cancer that friends and family have faced and the subsequent tests and treatments they have tolerated often with side effects and exhausting emotions.
Because screening for breast cancer is often centered on imaging—detecting whether a mass or calcification is visible on a radiologist’s screen—following up with biopsies remain the time-honored way to confirm cancer. But in 80 percent of those undergoing biopsies, no cancer will be found, according to the American Cancer Society. False positives on mammography are common; estimates suggest that in women who obtain an annual mammogram over a 10-year period, half will receive a false-positive determination at some point, inciting alarm. Conversely, the high false negative rate (1 out of 8) of current screening methods misses cancers that require treatment.
Could there be a way to cut down on the false positives, and have a less worrisome, cost-effective way for practitioners to arrive at a diagnosis faster without biopsies or other testing? Finding cancers sooner with greater accuracy, especially for aggressive cancers, leads to earlier treatments and better outcomes may be realized.
The Walt Lab at Brigham and Women’s Hospital, with its 25 staff members, has come up with a blood biomarker test that when integrated with mammography may actually help patients avoid follow-up procedures like biopsies, CTs, ultrasounds and MRIs, and the delays in needed treatment that may follow.
Starting in 2016, the team has worked with a panel of 24 biomarkers (biologic molecules found in blood to identify conditions) of proteins to test for breast cancer in women, which yielded an 87 percent accuracy rate. (A previous study on mice showed the panel detected an early tumor that extrapolated would be only 1 mm in diameter in humans.)
Differentiating this blood test for cancer
Blood tests for cancer are not new; in fact, there are lots of blood tests for cancer. They typically look at DNA coming from cancer cells—called cell-free DNA. Most of the tests can detect a variety of cancers but with varying sensitivities and specificities. Breast cancer has been one that has not had good sensitivity to date.
Yet simply detecting breast cancer is insufficient. Physicians need to be able to subtype the cancer into whether it is estrogen-receptor positive, progesterone-receptor positive, and/or HER2-receptor positive because the different subtypes require different treatments. Typically, subtyping is done by biopsy of the tumor and sent to pathology for staining and analysis.
Walt’s test, however, is aimed at both detecting the presence of breast cancer and its subtype. The individual protein assays are 1000 times more sensitive than in other tests.
Presently, the inability to differentiate aggressive from indolent, or slow-growing cancer, is a clinical problem that leads to overdiagnosis and overtreatment. With the blood test, some cancers might be watched over time by physicians, suggesting that immediate treatment would not be indicated. But ideally, no biopsy would be taken.
The lab’s goal is on greater accuracy from the technology, perhaps 95 percent. To that end, the team has begun identifying and exploring an additional 50 biomarkers and plans to run human samples to test them.
A collaboration formed with Canon Medical Systems
Canon Medical Systems, a global leader of diagnostic imaging equipment, has been interested in the technology, and a Mass General Brigham collaborative project is currently in the works, thanks in part to Seema Basu, PhD, Strategic Innovation Leader.
“This is a very exciting collaboration,” says Basu. “We value industry alliances that enable us to bring together complementary resources and expertise to accelerate discoveries and projects such as this one towards solutions for patients.”
“Seema was instrumental in putting together this collaboration,” says Walt. “She served as a ‘matchmaker’ of sorts to produce this collaboration with Canon.” Walt also gives a shout out to Hui Wang, PhD, Senior Manager, Business Development and Licensing at Mass General Brigham Innovation. “She has been super helpful in keeping this project on track.”
More studies will be conducted. Under consideration is participating with the Nurses Health Study, one of the largest investigational studies for risk factors for chronic disease. The team also plans to collect samples from 600 women presenting for mammograms at Brigham and Women’s Faulkner Hospital. Sampling will be completed at the end of the year and then analyzed.
Funding and assistance from visiting scientists at Canon complement the five-year grant the team has already received from the U.S. Department of Defense’s Congressionally Directed Medical Research Program on breast cancer, about $5 million. The program accelerates high-impact research with clinical relevance, encouraging innovation and stimulating creativity to address the end of breast cancer.
Canon has been conducting advanced technology research with Massachusetts General Hospital and Brigham and Women’s Hospital for more than a decade. “We are thrilled to be part of this innovation journey with Dr. David Walt, and look forward to bringing impactful contributions to patient diagnosis and clinical workflow,” says Sarika Verma, PhD, from the Collaborative Innovation Center of Canon Medical Research USA.
Yet the Walt Lab is not solely focused on breast cancer. Comprised of scientists, engineers, chemists, biologists, biomedical engineers, computer scientists, and physicians, the lab is also developing new technologies focused on diagnosing disease processes for infectious diseases and neurodegenerative diseases.
Walt’s other innovations
Walt is an accomplished innovator; his previous pioneering work on microwell arrays for single-molecule detection and genetic measurements has revolutionized the process of genetic and proteomic analysis, enabling the cost of DNA sequencing and genotyping to plummet nearly a millionfold in the last decade. Earlier this month, Walt was awarded the 2023 Fritz J. and Dolores H. Russ Prize by the National Academy of Engineering for his work in the development of microwell arrays.
Walt serves on the Brigham Ignite Executive Steering Committee, and has affiliations with Dana Farber Cancer Institute, the Broad Institute, and the Wyss Medical Institute at Harvard University. He is the scientific founder of Illumina; its technology is used by popular genotyping services like 23andMe, which analyze DNA for ancestry composition and genetic health risks. He has also founded Quanterix, and has co-founded multiple other life sciences startups including Ultivue, Arbor Biotechnologies, Sherlock Biosciences, Vizgen, and Torus Biosciences.
In addition to his passions–four grandchildren, first, then deep-sea fishing from his Rockport home–Walt is very proud of his team members who have been trained and are being trained at the lab and who are now involved in developing important innovations.
“I live and love science,” he says. “It’s a privilege to have a career where you can discover and invent things that sometimes can solve patient problems, moving the needle so that we reduce the disease burden,” he says. “I do this happily with great colleagues and collaborations.”
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