{"entity":{"id":"her2-ultralow","kind":"biomarker","name":"HER2-ultralow (IHC 0 with membrane staining)","aka":["HER2-ultralow","HER2 ultralow","ultralow","IHC 0 with faint staining","IHC >0 <1+"],"tldr":"HER2-ultralow is an IHC 0 result with a trace of membrane staining in a few cells. Since 2025, in hormone-receptor-positive breast cancer that has stopped responding to hormone therapy, it is enough for trastuzumab deruxtecan.","summary":"Ultralow is faint, incomplete membrane staining in 10 percent or fewer of tumour cells, a sub-band of the ASCO/CAP 0 score. DESTINY-Breast06 enrolled HER2-low and ultralow HR-positive metastatic breast cancer after endocrine therapy and showed a progression-free survival benefit over chemotherapy; the US label was amended in January 2025 and the FDA companion diagnostic list carries the PATHWAY 4B5 antibody with the detail 'HER2 ultralow expression (IHC 0 with membrane staining)'. Reproducibility between pathologists at this end of the scale is low, which is why re-review of 0 slides is often requested.","asOf":"2026-09-23","links":[{"label":"ENHERTU prescribing information (DailyMed)","url":"https://dailymed.nlm.nih.gov/dailymed/drugInfo.cfm?setid=7e67e73e-ddf4-4e4d-8b50-09d7514910b6"}],"tags":["biomarker","her2"],"related":["her2-ihc-0","her2-low-ihc"],"cancers":["her2-low-metastatic-breast-cancer","breast-hr-positive","tnbc"],"sections":[],"technologies":[],"targets":[],"drugs":["trastuzumab-deruxtecan","her2-testing-assays"],"companies":[],"institutions":[],"pathways":[],"terms":["her2-low","ihc"],"trials":[],"people":[],"bottlenecks":[],"keyPapers":["paper-boissiere-michot-her2-ultralow-tnbc-virchows-arch-2026"],"journals":[],"dependsOn":[],"notes":["Triple-negative breast cancer: ultralow (IHC 0 with faint incomplete membrane staining in 10% or fewer cells) was 37.6% of 367 untreated TNBCs, with 38.4% null (Boissiere-Michot 2026). DESTINY-Breast06 enrolled hormone receptor-positive disease only, so the ultralow label does not extend to TNBC; ultralow status carried no prognostic weight in TNBC."],"target":"her2","measurement":"ihc-score","scoringRule":{"text":"IHC 0 with faint, incomplete membrane staining in 10 percent or fewer of tumour cells; distinguished from IHC 0 with no staining.","quote":"HER2 ultralow expression (IHC 0 with membrane staining)","source":"https://www.fda.gov/medical-devices/in-vitro-diagnostics/list-cleared-or-approved-companion-diagnostic-devices-in-vitro-and-imaging-tools","sourceLabel":"FDA: List of FDA-Authorized Companion Diagnostic Devices"},"thresholds":[{"value":"IHC 0 with membrane staining, HR-positive, after endocrine therapy","drugId":"trastuzumab-deruxtecan","cancerId":"her2-low-metastatic-breast-cancer","regulator":"FDA","source":"https://dailymed.nlm.nih.gov/dailymed/drugInfo.cfm?setid=7e67e73e-ddf4-4e4d-8b50-09d7514910b6","quote":"Select patients for treatment of unresectable or metastatic HER2-low (IHC 1+ or IHC 2+/ISH-) or HER2-ultralow (IHC 0 with membrane staining) breast cancer with ENHERTU based on HER2 expression","status":"current"}],"tests":[],"assays":["her2-herceptest","her2-pathway-4b5"],"companionDiagnostics":[{"device":"PATHWAY anti-Her2/neu (4B5) Rabbit Monoclonal Primary Antibody","maker":"Ventana Medical Systems (Roche)","drugs":["trastuzumab-deruxtecan"],"indication":"Breast Cancer - Tissue","pma":"P990081/S055 (01/27/2025)","source":"https://www.fda.gov/medical-devices/in-vitro-diagnostics/list-cleared-or-approved-companion-diagnostic-devices-in-vitro-and-imaging-tools"}],"forPatient":"If your hormone-receptor-positive breast cancer was scored HER2 0, ask the pathologist whether any membrane staining was seen. If so it is ultralow, and trastuzumab deruxtecan is on label after hormone therapy stops working; if there was none, it is not."},"route":"/biomarkers/her2-ultralow/","neighbours":{"biomarker":[{"id":"her2-ihc-0","kind":"biomarker","name":"HER2 IHC 0 (HER2-negative, including ultralow)","route":"/biomarkers/her2-ihc-0/"},{"id":"her2-ihc-3-plus","kind":"biomarker","name":"HER2 IHC 3+ (HER2-positive by immunohistochemistry)","route":"/biomarkers/her2-ihc-3-plus/"},{"id":"her2-low-ihc","kind":"biomarker","name":"HER2-low (IHC 1+ or IHC 2+/ISH-negative)","route":"/biomarkers/her2-low-ihc/"}],"cancer":[{"id":"her2-low-metastatic-breast-cancer","kind":"cancer","name":"HER2-low and HER2-ultralow metastatic breast cancer","route":"/cancers/her2-low-metastatic-breast-cancer/"},{"id":"breast-hr-positive","kind":"cancer","name":"HR-positive / HER2-negative breast cancer","route":"/cancers/breast-hr-positive/"},{"id":"tnbc","kind":"cancer","name":"Triple-negative breast cancer (TNBC)","route":"/cancers/tnbc/"}],"drug":[{"id":"her2-testing-assays","kind":"drug","name":"HER2 IHC and ISH companion assays (HercepTest, PATHWAY 4B5, HER2 Dual ISH)","route":"/drugs/her2-testing-assays/"},{"id":"trastuzumab-deruxtecan","kind":"drug","name":"Trastuzumab deruxtecan","route":"/drugs/trastuzumab-deruxtecan/"}],"term":[{"id":"her2-low","kind":"term","name":"HER2-low and HER2-ultralow","route":"/terms/her2-low/"},{"id":"ihc","kind":"term","name":"Immunohistochemistry (IHC)","route":"/terms/ihc/"}],"paper":[{"id":"paper-schettini-her2-low-features-npj-breast-cancer-2021","kind":"paper","name":"Clinical, pathological, and PAM50 gene expression features of HER2-low breast cancer","route":"/key-papers/paper-schettini-her2-low-features-npj-breast-cancer-2021/"},{"id":"paper-boissiere-michot-her2-ultralow-tnbc-virchows-arch-2026","kind":"paper","name":"Exploring the spectrum of HER2 in non-metastatic triple negative breast cancer: from HER2-null to HER2-low, including HER2-ultralow status","route":"/key-papers/paper-boissiere-michot-her2-ultralow-tnbc-virchows-arch-2026/"}],"target":[{"id":"her2","kind":"target","name":"HER2","route":"/targets/her2/"}],"roadmap":[{"id":"tnbc-roadmap","kind":"roadmap","name":"Triple-negative breast cancer roadmap: from a remainder defined by three negative tests to immunotherapy, antibody-drug conjugates and the residual disease problem","route":"/roadmaps/tnbc-roadmap/"}],"idea":[{"id":"idea-tnbc-her2-ultralow-testing-uptake","kind":"idea","name":"Reflex re-scoring of HER2 0 versus 1+ with digital assistance so every eligible triple-negative patient reaches trastuzumab deruxtecan","route":"/ideas/idea-tnbc-her2-ultralow-testing-uptake/"}]}}