Titles and Affiliations
Anthony N. Brady Professor of Pathology
Professor of Medical Oncology
Director, Yale Cancer Center Tissue Microarray Facility and Pathology Tissue Services
Pathology Research Professor, Department of Pathology
Research area
Developing more accurate assays to help clinicians personalize breast cancer treatment by matching patients with the best treatment for their breast cancer.
Impact
Chemotherapy can reduce the risk of recurrence of breast cancer, but there is no way to tell which patients will benefit. Clinicians face a similar challenge in determining which patients will benefit from targeted therapies including newer drugs called antibody-drug conjugates (ADCs). Dr. Rimm and his team are conducting several studies that focus on optimizing testing strategies to match patients to treatment more effectively. Dr. Rimm’s lab has demonstrated that an inexpensive test that measures the presence of a proliferation marker called Ki67 in tumor biopsies can identify which patients need chemotherapy, sparing those who do not the added side effects and cost of unnecessary treatment. His lab has also used novel methods to assess tumor infiltrating lymphocytes (TILs), a measure of the immune system status to better determine which patients will benefit from immunotherapy and may be able to forgo chemotherapy. Most recently, Dr. Rimm has leveraged his expertise in developing sensitive assays to match patients to newly approved antibody-drug conjugates (ADCs). The results of his studies can then be translated to the clinic to provide patients with the optimum treatment for their breast cancer.
Progress Thus Far
With BCRF funding, Dr. Rimm and his team developed a new assay that accurately and precisely measures protein targets of two ADCs—T-DXd (Enhertu®) and Sacituzumab govitecan (Trodelvy®)–that are FDA-approved for use in the metastatic setting: The Troplex™ assay tags HER2 and Trop2, flagging them with different markers, and enabling pathologists to precisely measure the amount of HER2 and TROP2 protein on tumor cells. Dr. Rimm’s team launched two clinical trials to validate Troplex™, the QuantifyHER trial and a separate trial to assess Trop2 levels, both conducted through the Translational Breast Cancer Research Consortium (TBCRC).
What’s next
In the coming year, the Rimm team will continue to focus on a range of different ADC targets relevant to breast cancer and then build assays to measure them. In other studies, they are looking at triple-negative breast cancer (TNBC), a particularly aggressive with limited treatment options. In TNBC, the immune system’s activity, particularly the number and type of lymphocytes in the tumor microenvironment, can shape how the cancer behaves, either controlling it or allowing it to progress. This makes the immune system a key player in TNBC biology. Dr. Rimm and his colleagues will assess the extent of TIL infiltration, which may help determine which patients receive which chemotherapy. Specifically, the team is working with the Southwest Oncology Group in a trial to determine if there is a level of TILs above which patients can be spared from toxic chemotherapy. In addition, his group will develop an assay to measure TILs and to increase the precision of the current pathology methods. Ultimately, Dr. Rimm hopes his studies will help advance precision medicine, providing sensitive assays to detect specific targets on breast tumor cells and tailor treatments to each patient.
If not for BCRF we would not have been able to produce and validate the quantitative ADC selector assay, which will help get the right drug to the right patients with metastatic breast cancer.
Biography
David Rimm, MD, PhD is a Professor in the Department of Pathology at the Yale University School of Medicine with a secondary appointment in Medicine (Oncology). He completed an MD-PhD at Johns Hopkins University Medical School followed by a Pathology Residency at Yale and a Cytopathology Fellowship at the Medical College of Virginia.
His lab group focuses on quantitative pathology using the AQUA® technology invented in his lab with projects related to predicting response to therapy, recurrence or metastasis in breast cancer. He is a member of a number of correlative science committees for multi-institutional breast cancer clinical trials including SWOG, ALLTO, and TEACH. He also serves on the Molecular Oncology committee for the College of American Pathologists. He is an author of over 280 peer-reviewed papers and 8 patents. He has served on advisory boards for Genentech, Novaritis, BMS, Perkin Elmer, Dako, ACD, Avida, OptraScan, Metamark Genetics and Genoptix.
