Yale pathology researchers created a dependable test that precisely measures key proteins found in breast cancer cells that can help oncologists choose the most effective targeted therapies for patients, says a report published July 16 in Precision Oncology, a journal of the American Society of Clinical Oncology.
The assay, named Troplex™, was designed to help guide physician decision making by providing detailed information about the exact level of HER2 and TROP2 proteins in each patient’s tumor. Knowing those levels reveals the biology of the tumor, which can be used to determine which antibody-drug conjugate (ADC) would provide the most beneficial treatment, the study says.
“There is currently no way to choose between two targeted therapies with the same indication in advanced cancer. This assay provides a solution to that problem,” says senior author David L. Rimm, MD, PhD, Anthony N. Brady Professor of Pathology and professor of medicine (medical oncology) at Yale School of Medicine.
In addition to Rimm, nine researchers from the Department of Pathology, led by graduate student Jack Robbins, are authors of the study.
The biomarkers chosen for this report, HER2 and TROP2, typically are present in breast cancers for which there are three new ADCs approved by the Food and Drug Administration (FDA).
The study notes there is more than the usual amount of HER2 present in about 15-20% of breast cancers, in which case patients might benefit from a HER2-targeting drug called trastuzumab deruxtecan that has shown significant results, including improved survival rates compared to standard of care chemotherapy.
Similarly, TROP2 is “overexpressed” across many cancers, including triple-negative breast cancers associated with aggressive growth, metastasis, and poor prognoses. The FDA recently approved a drug that targets TROP2, sacituzumab govitecan, for use on certain metastatic breast cancers, including triple-negative breast cancer.
The study applied Troplex to hundreds of breast cancer cases and generated percentile scores to indicate a tumor's protein expression to show the potential for use of the assay to select the therapy biologically most likely to help the patients.
"The novelty of this assay is that it uses multiplex fluorescence and standardization to provide a measurement of the number of drug target molecules for two drug targets on a single slide,” says Rimm, a member of the Yale Cancer Center.
While recognizing limitations of the study, including that knowing exact amounts of these proteins does not yet correlate to a patient's specific response to treatment, trials are ongoing. Preliminary data from Rimm’s lab and others suggests that the levels of target will be directly and tightly correlated to ADC response.
The research reported in this news article was supported by the Breast Cancer Research Foundation, National Institutes of Health (awards P30CA016359 and F30CA287869), and Yale University. The content is solely the responsibility of the authors and does not necessarily represent the official views of the National Institutes of Health.