Dr Rimm on the Limitations of HER2 IHC Assays in Breast Cancer

David Rimm, MD, PhD, Anthony N. Brady Professor of Pathology, professor, medicine, Medical Oncology, Yale School of Medicine; director, Physician Scientist Training Program, Pathology Research, director, Tissue Microarray Facility, director, Yale Pathology Tissue Services, Pathology, Yale Cancer Center, discusses the limitations of current HER2 immunohistochemistry (IHC) assays in breast cancer, and how inaccurate testing results impact outcomes for patients with low HER2 expression.

Rimm begins by clarifying that the IHC test for HER2 is a companion diagnostic rather than a standard diagnostic test, meaning it is specifically used to determine eligibility for certain therapies. In this case, the companion diagnostic is primarily associated with the agent fam-trastuzumab deruxtecan-nxki (Enhertu; T-DXd), he adds. T-DXd is a highly effective drug that has significantly improved treatment outcomes for patients with HER2-low or HER2-positive cancers, Rimm states. However, the ability of this diagnostic test to accurately identify patients who have the potential to benefit from HER2-targeted therapies such as T-DXd remains a concern, he emphasizes.

The test categorizes HER2 expression levels, and patients are classified as HER2 0, 1+, 2+, or 3+. However, this grading system isn't always precise, Rimm notes. One major issue is that patients identified as 1+ may actually have no detectable HER2 expression, yet they might still be given the drug, which would provide little or no therapeutic benefit, Rimm explains. On the other hand, some patients classified as IHC 0 may have enough HER2 expression to benefit from the treatment but are excluded due to insufficient HER2 detection by the IHC test, he details. This diagnostic inaccuracy results in potentially effective therapy being withheld from patients who could respond well to it, Rimm concludes.

The limitations of the IHC test highlight a gap between diagnostic precision and the potential for therapeutic benefit, Rimm summarizes. As HER2-targeted therapies continue to expand, refining the accuracy of companion diagnostics becomes increasingly important. Ensuring that the right patients are selected for treatment using more reliable detection methods could further enhance outcomes and expand the reach of these agents.