David Rimm, MD, PhD

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 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 a 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 antibody-drug conjugates. Taken together, the results of these studies can be translated to the clinic to provide patients with the optimum treatment for their breast cancer.

Progress Thus Far

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 also used novel methods to assess tumor infiltrating lymphocytes (TILs), a measure of the immune system status in breast cancer biopsy specimens to better determine which patients will benefit from immunotherapy and forgo chemotherapy. Most recently, Dr. Rimm developed a new assay for accurate assessment of low HER2 protein levels to match patients with the new antibody drug conjugate (ADC), T-DXd, which has been approved in the metastatic setting for HER2-positive patients including those designated as HER2-low.,. 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 TNBC.

What’s next

Dr. Rimm will continue developing objective methods for assessing tumor infiltrating lymphocytes (TILs) which can indicate the likelihood of response to therapy in triple-negative breast cancer (TNBC). His team is looking at AI-based computational approaches to best capture the prognostic value of TILs. Dr. Rimm hopes that this tool can ultimately help to determine which patients with TNBC could forego chemotherapy. 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. Using several of the analytic tools in the chemistry toolbox His team hopes to develop more accurate methods to personalize treatment and determine who should receive which drugs and in which order.