Rethinking HER2: A Pan-Cancer Look at IHC, ERBB2, and Tumor-Agnostic Testing

HER2 has long been synonymous with breast cancer, but a growing body of evidence shows it's expressed, at some level, across nearly every solid tumor type. In this episode of Targeted Talks, host Sabrina Serani sits down with Dr Aditya Shreenivas (City of Hope National Medical Center) and Dr Razelle Kurzrock (Medical College of Wisconsin Cancer Center) to unpack their new real-world analysis, published in ESMO Open, using data made available by Caris Life Sciences, examining HER2 immunohistochemistry (IHC) expression and ERBB2 alterations across more than 200,000 tumors.

The conversation traces how HER2 evolved from a breast cancer biomarker to a tumor-agnostic target, following the accelerated approval of fam-trastuzumab deruxtecan (T-DXd; Enhertu) for HER2 IHC 3+ solid tumors. Drs Shreenivas and Kurzrock walk through the study's key findings: how ERBB2 amplification and mutation status each relate to HER2 IHC expression, why that relationship is more complex—and more clinically important—for mutations than for amplifications, and what it means when the biomarkers disagree. They also dig into overall survival data showing that the prognostic benefit of high HER2 expression is largely concentrated in breast and gastric cancers, where HER2-targeted therapies are already standard of care, vs rarer tumor types like salivary gland and endometrial cancer, where the picture looks different.

Listeners will come away with a clearer sense of why HER2 should be treated as a continuous variable rather than a binary positive/negative result, why routine HER2 IHC testing matters for every patient with unresectable or metastatic disease, and where the open questions remain, including discordant cases where amplification and IHC don't line up.

A must-listen for oncologists, pathologists, and researchers working across breast, GI, gynecologic, and rare solid tumors who want a real-world, pan-cancer view of the evolving HER2 landscape.