HER2-ultralow rescoring finds ~45% prevalence inside “HER2-0” advanced breast cancer

HER2-ultralow refers to IHC 0 tumors with faint/incomplete membrane staining, a boundary that may matter as trastuzumab deruxtecan extends HER2-directed ADC activity below classic HER2-low disease. In a Mayo Clinic digital-slide rescoring cohort of advanced breast cancer originally called HER2 IHC 0 (Stages III–IV; n=300), 95% remained IHC 0 by at least one pathologist, but ~60% of those met HER2-ultralow criteria by at least one pathologist; per-reader ultralow prevalence was 43%–45%, with only 57% inter-pathologist concordance. Treatment patterns were similar between HER2-ultralow and “no observable staining,” and TTF differences were modest/noisy across HR+ and HR− subgroups, so the bigger finding is diagnostic reproducibility rather than evidence that ultralow biology alone changes outcomes.