Yale School of Medicine New Haven, Connecticut
Professor, Department of Pathology Director, Pathology Tissue Services Director, Translational Science in Pathology
To assess diagnostic tests that would help clinicians personalize breast cancer treatment by matching patients with the best treatment for their breast cancer.
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 new immunotherapy drugs. Dr. Rimm and his team are conducting several studies that focus on optimizing testing strategies to match patients to treatment more effectively. This includes tumor infiltrating lymphocyte (TIL) assessment that could identify patients with triple-negative breast cancer who may benefit from immunotherapies, a common tumor marker called Ki67 that can select patients for chemotherapy, and a more precise test to measure HER2 levels to match patients to a newly approved drug. Taken together, the results of these studies can be translated to the clinic to provide patients with the optimum treatment for their breast cancer.
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. While the potential of Ki67 as a tumor marker has been unclear, Dr. Rimm’s efforts to standardize the test may make it comparable to the Oncotype DX test at less than one-tenth of the cost. His lab has used novel methods to assess the immune system status (TIL score) in breast cancer biopsy specimens to better determine which patients will benefit from immunotherapy and forgo chemotherapy. Antibody drug conjugate (ADC), T-DXd, has been approved in the metastatic setting for HER2-positive patients including those designated as HER2-low. Current tools for determining HER2 levels are not sensitive enough to detect low levels of HER2 protein that may be recognized by T-DXd. For that reason, Dr. Rimm developed a new assay for accurate assessment of low HER2 protein levels.
Dr. Rimm will continue to work toward optimizing Ki67 for wider use in the clinic to determine which patients can avoid chemotherapy and validate an updated algorithm he has developed for automated TIL assessment. The Rimm lab will also continue to refine the assay for HER2-low detection, explore the biology of the HER2-low subtype, and conduct digital spatial profiling to distinguish the characteristics of high, low, and zero HER2 levels. Similar studies are underway to develop a quantitative diagnostic test to assess which patients will benefit from Sacituzumab Govitecan, an ADC that is approved for the treatment of metastatic triple-negative breast cancer. Dr. Rimm will employ several of the analytic tools in the chemistry toolbox to develop more accurate methods to personalize treatment and determine who should receive these new drugs for metastatic breast cancer and in which order they should receive them.
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.
2012
The Housewares Charity Foundation Award
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