Is HER2-Low a New Clinical Entity or Merely a Biomarker for an Antibody Drug Conjugate?

Following the FDA's approval of trastuzumab deruxtecan (T-DXd) for advanced HER2-low breast cancer, there's debate on whether HER2-low should be a distinct clinical category or just a biomarker for specific treatments. Recognizing HER2-low as a separate subtype would necessitate revising clinical guidelines for HER2 scoring and testing in breast cancer, as well as therapeutic indications. This editorial reviews available data on HER2-low breast cancer and discusses recent updates from the ASCO/CAP guidelines on distinguishing HER2-low from HER2-negative breast cancer.