[{"data":1,"prerenderedAt":-1},["ShallowReactive",2],{"detail-sidebar-cat-0-en-105":3,"doc-seo-450502-105":59,"doc-detail-450502-en":130},{"code":4,"msg":5,"data":6},0,"success",[7,13,18,23,28,33,38,43,48,51,55],{"id":8,"doc_module":4,"doc_module_name":9,"category_name":10,"show_sort_weight":11,"slug":12},1,"Document","Story & Novel",90,"story-novel",{"id":14,"doc_module":4,"doc_module_name":9,"category_name":15,"show_sort_weight":16,"slug":17},2,"Literature",80,"literature",{"id":19,"doc_module":4,"doc_module_name":9,"category_name":20,"show_sort_weight":21,"slug":22},4,"Exam",70,"exam",{"id":24,"doc_module":4,"doc_module_name":9,"category_name":25,"show_sort_weight":26,"slug":27},5,"Comic",60,"comic",{"id":29,"doc_module":4,"doc_module_name":9,"category_name":30,"show_sort_weight":31,"slug":32},6,"Technology",50,"technology",{"id":34,"doc_module":4,"doc_module_name":9,"category_name":35,"show_sort_weight":36,"slug":37},7,"Healthcare",40,"healthcare",{"id":39,"doc_module":4,"doc_module_name":9,"category_name":40,"show_sort_weight":41,"slug":42},8,"Research & Report",30,"research-report",{"id":44,"doc_module":4,"doc_module_name":9,"category_name":45,"show_sort_weight":46,"slug":47},9,"Religion & Spirituality",20,"religion-spirituality",{"id":46,"doc_module":4,"doc_module_name":9,"category_name":49,"show_sort_weight":46,"slug":50},"World Cup","world-cup",{"id":52,"doc_module":4,"doc_module_name":9,"category_name":53,"show_sort_weight":52,"slug":54},10,"Lifestyle","lifestyle",{"id":56,"doc_module":4,"doc_module_name":9,"category_name":57,"show_sort_weight":24,"slug":58},19,"General","general",{"code":4,"msg":60,"data":61},"ok",{"site_id":62,"language":63,"slug":64,"title":65,"keywords":66,"description":67,"schema_data":68,"social_meta":123,"head_meta":125,"extra_data":127,"updated_unix":129},105,"en","her2-expression-in-breast-cancer-evidence-gaps-and-challenges","HER2 expression in breast cancer - evidence gaps and challenges","","HER2-based classification in breast cancer is shifting as therapeutic response depends on the level of HER2 protein expression rather than a simple HER2-positive versus HER2-negative dichotomy. Breast cancers are now scored by immunohistochemistry into five subgroups, creating key treatment groups such as HER2-positive (IHC 2+ amplified and 3+) and HER2-negative, further subdivided into HER2-Low (IHC 1+ and 2+ non-amplified) and HER2-null (IHC 0). Emerging antibody-drug conjugate data, especially T-DXd, highlight differential outcomes across the HER2 spectrum and challenge the traditional diagnostic role of HER2. ",{"@graph":69,"@context":122},[70,84,105],{"@type":71,"itemListElement":72},"BreadcrumbList",[73,77,79,82],{"item":74,"name":75,"@type":76,"position":8},"https://docshare.wps.com","Home","ListItem",{"item":78,"name":9,"@type":76,"position":14},"https://docshare.wps.com/document/",{"item":80,"name":35,"@type":76,"position":81},"https://docshare.wps.com/document/healthcare/",3,{"item":83,"name":65,"@type":76,"position":19},"https://docshare.wps.com/document/her2-expression-in-breast-cancer-evidence-gaps-and-challenges/450502/",{"url":83,"name":65,"@type":85,"image":86,"author":91,"headline":65,"publisher":94,"fileFormat":97,"inLanguage":63,"description":67,"dateModified":98,"datePublished":99,"encodingFormat":97,"isAccessibleForFree":100,"interactionStatistic":101},"DigitalDocument",{"url":87,"@type":88,"width":89,"height":90},"https://docshare.wps.com/thumbnails/her2-expression-in-breast-cancer-evidence-gaps-and-challenges/450502.png","ImageObject",300,407,{"name":92,"@type":93},"Damian","Person",{"url":74,"name":95,"@type":96},"DocShare","Organization","application/pdf","2026-10-30","2026-09-30",true,{"@type":102,"interactionType":103,"userInteractionCount":34},"InteractionCounter",{"@type":104},"ViewAction",{"@type":106,"mainEntity":107},"FAQPage",[108,114,118],{"name":109,"@type":110,"acceptedAnswer":111},"How is HER2 expression in breast cancer reclassified, and why does it matter clinically?","Question",{"text":112,"@type":113},"HER2 status is scored using immunohistochemistry and, when appropriate, in situ hybridisation. New evidence supports multiple HER2 subgroups that better reflect differences in therapeutic response, particularly for ADC-based treatments.","Answer",{"name":115,"@type":110,"acceptedAnswer":116},"What distinguishes HER2-positive from HER2-negative categories under current scoring?",{"text":117,"@type":113},"HER2-positive includes IHC 3+ and IHC 2+ cases with HER2 gene amplification on reflex ISH testing. HER2-negative includes IHC 0 and IHC 1+, as well as IHC 2+ non-amplified tumors.",{"name":119,"@type":110,"acceptedAnswer":120},"What role do ADCs such as T-DXd play in defining HER2-Low disease?",{"text":121,"@type":113},"T-DXd can deliver potent cytotoxic agents to cells with low HER2 levels, enabling recognition of the HER2-Low concept. This drives reassessment of the clinical significance of HER2 categories along the full expression spectrum.","https://schema.org",{"og:url":83,"og:type":124,"og:title":65,"og:site_name":95,"og:description":67},"article",{"robots":126,"canonical":83},"index,follow",{"doc_id":128,"site_id":62},450502,1790953602,{"code":4,"msg":5,"data":131},{"doc_id":128,"user_id":132,"nickname":92,"user_avatar":133,"doc_module":4,"category_id":34,"category_name":35,"doc_title":65,"doc_description":67,"doc_content":134,"file_id":135,"file_url":136,"file_type":137,"file_size":138,"view_count":34,"is_deleted":4,"is_public":8,"is_downloadable":8,"audit_status":8,"page_count":139,"language":140,"language_code":63,"site_id":62,"html_lang":63,"table_of_contents":141,"faqs":142,"seo_title":143,"seo_description":67,"update_tm":144,"read_time":145,"preview_page_count":4},137451208677,"https://ap-avatar.wpscdn.com/davatar_155a257f0dc6eb9ab79c44ca47cae57d","npj | precision oncology Review  \n\n| Published in partnership with The Hormel Institute, University of Minnesota |  | |\n| --- | --- | --- |\n| [https://doi.org/10.1038/s41698-025-01209-9](https://doi.org/10.1038/s41698-025-01209-9) |  |  |\n| HER2 expression in breast cancer: evidence gaps and challenges\u003Cbr> Check for updates |  |  |\n| Nehal M Atallah1,2, Cecily Quinn3 & Emad Rakha 1,2,4  |  |  |\n| The classification of breast cancer (BC) based on HER2 expression is undergoing significant changes. While traditional approaches have focused on HER2-positive and HER2-negative categories, emerging evidence highlights varied therapeutic responses depending on the level of HER2 protein expression. Breast cancers are now immunohistochemically (IHC) scored into five subgroups, which define two primary therapeutic groups: HER2-positive (IHC 2+ amplified and 3 + ) and HER2-negative (IHC 0, 1 + , and 2+ non-amplified) . Recent advances, particularly in antibody-drug conjugates (ADCs), have led to further subclassification of HER2-negative BC into HER2-Low and HER2-null (IHC 0). Also, for HER-positive subgroups, a differential response to HER2-targeted therapies is seen. This evolving landscape challenges the traditional use of HER2asa diagnostic marker and underscores the need fora deeper understanding of HER2biology. This review addresses these complexities, focusing on the emerging HER2-Low and Ultralow subtypes, and evaluates the distinct therapeutic responses across the spectrum of HER2 expression in different BC subtypes. |  |  |\n| HER2protein isan epidermal growth factor receptor(EGFR)ofthe tyrosine kinase family and forms heterodimers with other ligand-bound EGFR family members such as HER3 and HER4, which activates downstream signalling pathways to promote cell proliferation, cell invasion, angiogenesis and to protect cells against apoptosis (Fig. 1)1–3. Normal tissues have a low complement of HER2 membrane protein. Breast cancer (BC) tissue may have up to25–50copies ofthe HER2 gene and up to40–100fold increase in HER2protein resulting in up to2million receptors expressed atthe tumour cell surface4. Although HER2 overexpression confers a poor prognosis (due to the effect on cell proliferation, migration, invasion, and survival, all hallmarks of cancer), it offers a unique opportunity to utilise oncogenic therapies that target HER2, improving BC patient outcome5.\u003Cbr>In diagnostic pathology, the HER2status ofabreast tumour is assessed using a combination of immunohistochemistry (IHC) to evaluate HER2 protein expression levels, and/or in situ hybridisation (ISH) to assess HER2 gene status, the only two techniques currently validated for clinical use6,7. HER2positivityin BC is defined as protein overexpression(IHC score3 + ) or HER2 equivocal protein expression (IHC score of 2 + )with evidence of HER2 gene amplification on ISH reflex testing6. This scoring system was developed to predict response to anti-HER2 therapies such as trastuzumab8 that showed efficacy limited to patients with HER2-positive BC. According to this definition, tumours with equivocal HER2 expression without evidence of HER2 gene amplification and tumours with low or undetectable | levels of HER2 protein (IHC score 1+ or 0, respectively) are defined as HER2 negative to reflect the lack of response to anti-HER2 targeted therapies including trastuzumab and the antibody-drug conjugate (ADC) trastuzumab emtansine (T-DM1)9. Recently, the historical HER2 negative group has been sub-classified into2subgroups;HER2-Low(IHC score1 + , and2 + /ISH-negative)and HER20(IHC score0)toreflectthe difference in potential response to the novel HER2-based ADC therapy (trastuzumab deruxtecan (T-DXd)).\u003Cbr>T-DXd, which delivers potent cytotoxic agents to cells with low HER2 levels, has opened a new therapeutic option for this BC patient population and has led to recognition of the concept of HER2-Low BC9–11. Fig. 2 provides a chronological outline of the United States Food and Drug Administration (FDA) app","cbCaiti1TYreUi9o","https://ap.wps.com/l/cbCaiti1TYreUi9o","pdf",3446782,18,"English","# HER2-based classification shifts in breast cancer\n## HER2 biology and diagnostic assessment\n## HER2-Low and HER2-ultralow subtypes\n## Therapeutic implications and evidence gaps\n## Differential responses in HER2-positive disease","[{\"question\":\"How is HER2 expression in breast cancer reclassified, and why does it matter clinically?\",\"answer\":\"HER2 status is scored using immunohistochemistry and, when appropriate, in situ hybridisation. New evidence supports multiple HER2 subgroups that better reflect differences in therapeutic response, particularly for ADC-based treatments.\"},{\"question\":\"What distinguishes HER2-positive from HER2-negative categories under current scoring?\",\"answer\":\"HER2-positive includes IHC 3+ and IHC 2+ cases with HER2 gene amplification on reflex ISH testing. HER2-negative includes IHC 0 and IHC 1+, as well as IHC 2+ non-amplified tumors.\"},{\"question\":\"What role do ADCs such as T-DXd play in defining HER2-Low disease?\",\"answer\":\"T-DXd can deliver potent cytotoxic agents to cells with low HER2 levels, enabling recognition of the HER2-Low concept. This drives reassessment of the clinical significance of HER2 categories along the full expression spectrum.\"}]","HER2 expression in breast cancer - evidence gaps and challenges | PDF",1790733330,45]