{"entity":{"id":"her2-low-ihc","kind":"biomarker","name":"HER2-low (IHC 1+ or IHC 2+/ISH-negative)","aka":["HER2-low breast cancer","HER2-low readout","IHC 1+ or 2+/ISH-","HER2 low expression","HER2-low (IHC 1+ or IHC 2+/ISH-)"],"tldr":"HER2-low is not a new stain but a new reading of the old one: 1+ or 2+ without gene amplification. It covers about half of breast cancers and makes them eligible for trastuzumab deruxtecan.","summary":"HER2-low is defined in the trastuzumab deruxtecan label as IHC 1+ or IHC 2+ with a negative in situ hybridisation result, determined by an FDA-authorised test. DESTINY-Breast04 (2022) established the category in metastatic breast cancer after one or two lines of chemotherapy, and DESTINY-Breast06 (2025) extended it, with HER2-ultralow, to HR-positive disease after endocrine therapy. The FDA companion diagnostic list carries the PATHWAY 4B5 antibody with the detail 'HER2-low expression (IHC 1+ or IHC 2+/ISH non-amplified)'. Outside breast cancer HER2-low is a trial category, not a label one.","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-1-plus","her2-ihc-2-plus","her2-ultralow"],"cancers":["her2-low-metastatic-breast-cancer","breast-hr-positive","tnbc-metastatic","breast-cancer"],"sections":[],"technologies":[],"targets":[],"drugs":["trastuzumab-deruxtecan","her2-testing-assays"],"companies":[],"institutions":[],"pathways":[],"terms":["her2-low","ihc","fish"],"trials":[],"people":[],"bottlenecks":[],"keyPapers":[],"journals":[],"dependsOn":[],"notes":[],"target":"her2","measurement":"ihc-score","scoringRule":{"text":"IHC 1+, or IHC 2+ with a non-amplified in situ hybridisation result, by an FDA-authorised HER2 assay.","quote":"HER2-low expression (IHC 1+ or IHC 2+/ISH non-amplified)","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 1+ or IHC 2+/ISH-","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":"HER2-low (IHC 1+ or IHC 2+/ISH-) breast cancer, as determined by an FDA-authorized test, who have received a prior chemotherapy in the metastatic setting or developed disease recurrence during or within 6 months of completing adjuvant chemotherapy","status":"current"}],"tests":[],"assays":["her2-herceptest","her2-pathway-4b5","her2-ish"],"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/S047 (09/30/2022)","source":"https://www.fda.gov/medical-devices/in-vitro-diagnostics/list-cleared-or-approved-companion-diagnostic-devices-in-vitro-and-imaging-tools"},{"device":"VENTANA HER2 Dual ISH DNA Probe Cocktail","maker":"Ventana Medical Systems (Roche)","drugs":["trastuzumab-deruxtecan"],"indication":"Breast Cancer - Tissue","pma":"P190031/S015 (05/15/2026)","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 breast cancer report says 1+, or 2+ with a negative ISH, it is HER2-low. That does not change first treatment, but once the cancer has spread and chemotherapy (or, for hormone-receptor-positive cancers, hormone therapy) has stopped working, trastuzumab deruxtecan is an on-label option. A report written before 2022 may only say 'HER2-negative'; the underlying score can be looked up."},"route":"/biomarkers/her2-low-ihc/","neighbours":{"biomarker":[{"id":"her2-ihc-0","kind":"biomarker","name":"HER2 IHC 0 (HER2-negative, including ultralow)","route":"/biomarkers/her2-ihc-0/"},{"id":"her2-ihc-1-plus","kind":"biomarker","name":"HER2 IHC 1+","route":"/biomarkers/her2-ihc-1-plus/"},{"id":"her2-ihc-2-plus","kind":"biomarker","name":"HER2 IHC 2+ (equivocal, reflex to ISH)","route":"/biomarkers/her2-ihc-2-plus/"},{"id":"her2-ihc-3-plus","kind":"biomarker","name":"HER2 IHC 3+ (HER2-positive by immunohistochemistry)","route":"/biomarkers/her2-ihc-3-plus/"},{"id":"her2-ultralow","kind":"biomarker","name":"HER2-ultralow (IHC 0 with membrane staining)","route":"/biomarkers/her2-ultralow/"}],"cancer":[{"id":"breast-cancer","kind":"cancer","name":"Breast cancer (all types)","route":"/cancers/breast-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-metastatic","kind":"cancer","name":"Metastatic triple-negative breast cancer","route":"/cancers/tnbc-metastatic/"}],"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":"fish","kind":"term","name":"FISH / ISH (in situ hybridisation)","route":"/terms/fish/"},{"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/"}],"target":[{"id":"her2","kind":"target","name":"HER2","route":"/targets/her2/"}]}}