Charles John Robbins III

Next-generation diagnostic approaches for HER2-low breast cancer and trastuzumab deruxtecan therapy: The current immunohistochemical (IHC) assays for determining HER2-low status are no better than a coinflip (due to an estimated 75% discordance rate amongst pathologists scoring 0 vs. 1+/2+). These legacy assays for HER2 were designed over 20 years ago to detect amplified HER2 cases, and are now are being wrongly applied to select patients for emerging HER2-low therapies (e.g. trastuzumab deruxtecan). In the Rimm lab, we have developed a solution: a high-sensitivity HER2 assay that is designed to quantify unamplified, low HER2 expression rather than rely on subjective semi-quantitative scoring by pathologists using legacy IHC assays. We plan to carefully evaluate the HS-HER2 assay and it's predictive value towards T-DXd response to in comparison to the legacy IHC assays. We expect that our results will encourage adoption of high-sensitivity, analytic assays for HER2 expression that oncologists can use to be certain their patients are receiving the best treatment option available. My research will also include investigating the biology of HER2-low breast cancer and the molecular mechanisms outside of HER2 expression associated with T-DXd antibody-drug conjugate response.

Mentor: David Rimm