Sarah L. Sammons, MD, Dana-Farber Cancer Institute, Boston, MA, explains the definition of HER2-ultralow breast cancer, how it differs from HER2-low disease, and its proportion within hormone receptor-positive breast cancers. Dr Sammons describes the evolution of HER2 biomarker classification over the past five years, with HER2-low defined as immunohistochemistry 1+ or 2+ with FISH non-amplified status. HER2-ultralow, which emerged as a clinically relevant biomarker following the DESTINY-Breast06 trial (NCT04494425) demonstrating benefit from trastuzumab deruxtecan (T-DXd), represents what was historically considered HER2-zero disease but includes any HER2 expression on tumor cells (less than 10% but greater than zero). This category requires pathologist confirmation of any HER2 expression in cancer cells, expanding the population of patients who may benefit from HER2-directed antibody-drug conjugate therapy. This interview took place at the San Antonio Breast Cancer Symposium (SABCS) 2025 Meeting in San Antonio, TX.
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