{"entity":{"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","aka":[],"tldr":"A 3,689-patient study showing that 36.6 percent of triple-negative tumours are HER2-low, that in triple-negative disease HER2-low tumours are biologically no different from HER2-zero ones, and that pathologists agree poorly on the score; the label matters only because a drug now depends on it.","summary":"Schettini, Chic, Brasó-Maristany, Paré and colleagues collected retrospective clinicopathological and PAM50 data from 3,689 patients with HER2-negative breast cancer. HER2-low (immunohistochemistry 1+ or 2+ without ERBB2 amplification) was more common in hormone receptor-positive disease (65.4 percent) than triple-negative disease (36.6 percent). Within hormone receptor-positive disease ERBB2 and luminal genes were more expressed in HER2-low than HER2 0 tumours, whereas in triple-negative disease no gene was differentially expressed by HER2 level; within HER2-low, ERBB2 levels were higher in hormone receptor-positive than triple-negative tumours; HER2-low was not associated with overall survival in either group; and reproducibility of the HER2-low call among pathologists was suboptimal.","asOf":"2026-09-24","links":[{"label":"NPJ Breast Cancer 2021","url":"https://doi.org/10.1038/s41523-020-00208-2"},{"label":"PubMed","url":"https://pubmed.ncbi.nlm.nih.gov/33397968/"}],"tags":["tnbc-evidence"],"related":["paper-destiny-breast04-nejm-2022","her2-low-ihc"],"cancers":["tnbc","breast-hr-positive","her2-low-metastatic-breast-cancer"],"sections":[],"technologies":["digital-pathology-ai"],"targets":["her2"],"drugs":["trastuzumab-deruxtecan"],"companies":[],"institutions":[],"pathways":[],"terms":["her2-low","her2-ultralow","ihc","pam50"],"trials":["destiny-breast04"],"people":["aleix-prat"],"bottlenecks":["b-biomarker-validation"],"keyPapers":[],"journals":[],"dependsOn":[],"notes":[],"journal":"NPJ Breast Cancer","year":2021,"doi":"10.1038/s41523-020-00208-2","pmid":"33397968","authors":"Schettini F, Chic N, Brasó-Maristany F, et al.","paperType":"observational","findings":["HER2-low in 36.6 percent of triple-negative vs 65.4 percent of hormone receptor-positive HER2-negative tumours.","No gene differentially expressed between HER2-low and HER2 0 triple-negative tumours; HER2-low not associated with overall survival.","Suboptimal inter-pathologist reproducibility of the HER2-low score."],"whatItMeans":"HER2-low is a drug eligibility label, not a biological subtype, in triple-negative disease; because a third of patients qualify for trastuzumab deruxtecan on a score pathologists disagree about, re-scoring and digital assistance for HER2 0 versus 1+ is a practical gap.","caveats":["Retrospective, multiple cohorts and scoring eras.","Predates the HER2-ultralow category and the DESTINY-Breast06 result in hormone receptor-positive disease."],"changedPractice":false,"participants":3689},"route":"/key-papers/paper-schettini-her2-low-features-npj-breast-cancer-2021/","neighbours":{"paper":[{"id":"paper-destiny-breast04-nejm-2022","kind":"paper","name":"DESTINY-Breast04: trastuzumab deruxtecan works in HER2-low breast cancer, creating a new treatable group","route":"/key-papers/paper-destiny-breast04-nejm-2022/"}],"biomarker":[{"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":"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/"}],"technology":[{"id":"digital-pathology-ai","kind":"technology","name":"Digital pathology & AI","route":"/technologies/digital-pathology-ai/"}],"target":[{"id":"her2","kind":"target","name":"HER2","route":"/targets/her2/"}],"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/"},{"id":"pam50","kind":"term","name":"PAM50 / intrinsic subtypes","route":"/terms/pam50/"}],"trial":[{"id":"destiny-breast04","kind":"trial","name":"DESTINY-Breast04","route":"/trials/destiny-breast04/"}],"person":[{"id":"aleix-prat","kind":"person","name":"Aleix Prat","route":"/people/aleix-prat/"}],"bottleneck":[{"id":"b-biomarker-validation","kind":"bottleneck","name":"Biomarkers are not validated or standardised","route":"/bottlenecks/b-biomarker-validation/"}],"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/"}]}}