{"entity":{"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","aka":[],"tldr":"Reclassifying 367 chemotherapy-naive triple-negative cancers put 38% in HER2-null, 38% in HER2-ultralow and 24% in HER2-low; the categories differed a little in size, grade and BRCA1 methylation but not in relapse over ten years.","summary":"367 patients with non-metastatic TNBC who never received chemotherapy were reclassified: HER2 0 tumours as HER2-null (no staining) or HER2-ultralow (10% or fewer cells with faint incomplete membrane staining); 1+ or non-amplified 2+ as HER2-low. 38.4% were null, 37.6% ultralow and 24.0% low. Ultralow tumours were more often associated with tertiary lymphoid structures (P 0.0259) and BRCA1 promoter methylation (P 0.0439) than low tumours, and were smaller and of lower stage and grade than null tumours. Age, nodal status, histology, molecular apocrine or basal-like phenotype, PIK3CA and PTEN status, CD3, CD20 and CD163 infiltrates and PD-L1 did not differ. Relapse-free survival at a median 10.3 years was unaffected by HER2 category.","asOf":"2026-09-24","links":[{"label":"Boissiere-Michot et al., Virchows Arch 2026: HER2-null, ultralow and low in 367 chemotherapy-naive non-metastatic TNBCs","url":"https://doi.org/10.1007/s00428-026-04425-1"},{"label":"PubMed","url":"https://pubmed.ncbi.nlm.nih.gov/41636845/"}],"tags":[],"related":["her2-ultralow","her2-low-ihc","her2-ihc-0"],"cancers":["tnbc","tnbc-early"],"sections":[],"technologies":[],"targets":["her2"],"drugs":[],"companies":[],"institutions":[],"pathways":[],"terms":["her2-low","ihc"],"trials":[],"people":[],"bottlenecks":[],"keyPapers":[],"journals":[],"dependsOn":[],"notes":[],"journal":"Virchows Archiv","year":2026,"doi":"10.1007/s00428-026-04425-1","pmid":"41636845","authors":"Boissiere-Michot F, Gudin-De-Vallerin A, Thezenas S, et al.","paperType":"observational","findings":["HER2-null 38.4%, ultralow 37.6%, low 24.0% of 367 TNBCs.","Ultralow tumours smaller, lower grade, more BRCA1 promoter methylation; no survival difference."],"whatItMeans":"Three-quarters of chemotherapy-naive TNBC would be low or ultralow by the DESTINY-Breast06 definitions, but ultralow is unlabelled in TNBC and carries no prognostic weight.","caveats":["Single French cohort of untreated patients, so favourable-risk.","Ultralow scoring has low inter-pathologist reproducibility."],"changedPractice":false,"participants":367},"route":"/key-papers/paper-boissiere-michot-her2-ultralow-tnbc-virchows-arch-2026/","neighbours":{"biomarker":[{"id":"her2-ihc-0","kind":"biomarker","name":"HER2 IHC 0 (HER2-negative, including ultralow)","route":"/biomarkers/her2-ihc-0/"},{"id":"her2-low-ihc","kind":"biomarker","name":"HER2-low (IHC 1+ or IHC 2+/ISH-negative)","route":"/biomarkers/her2-low-ihc/"},{"id":"her2-ultralow","kind":"biomarker","name":"HER2-ultralow (IHC 0 with membrane staining)","route":"/biomarkers/her2-ultralow/"}],"cancer":[{"id":"tnbc-early","kind":"cancer","name":"Early triple-negative breast cancer","route":"/cancers/tnbc-early/"},{"id":"tnbc","kind":"cancer","name":"Triple-negative breast cancer (TNBC)","route":"/cancers/tnbc/"}],"target":[{"id":"her2","kind":"target","name":"HER2","route":"/targets/her2/"}],"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/"}],"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/"}]}}