[{"data":1,"prerenderedAt":-1},["ShallowReactive",2],{"doc-seo-373965-105":3,"detail-sidebar-cat-0-en-105":85,"doc-detail-373965-en":134},{"code":4,"msg":5,"data":6},0,"ok",{"site_id":7,"language":8,"slug":9,"title":10,"keywords":11,"description":12,"schema_data":13,"social_meta":78,"head_meta":80,"extra_data":82,"updated_unix":84},105,"en","standardizing-the-pathologic-assessment-of-her2-ultralow-breast-cancer-insights-from-a-national-italian-project","Standardizing the pathologic assessment of HER2-(ultra)low breast cancer - insights from a national Italian project","","Novel therapies for HER2-(ultra)low breast cancer have shifted HER2 status from a simple binary system to a multi-tier framework defined by immunohistochemistry (IHC). Pre-analytical and analytical variables can affect accurate identification of HER2 expression at the lowest IHC range. A national Italian project evaluated diagnostic challenges and classification practices through surveys, whole-slide image scoring, and on-site discussions, then compared results with an expert panel. Agreement was substantial overall but decreased in the most challenging ultralow spectrum cases.",{"@graph":14,"@context":77},[15,34,56],{"@type":16,"itemListElement":17},"BreadcrumbList",[18,23,27,31],{"item":19,"name":20,"@type":21,"position":22},"https://docshare.wps.com","Home","ListItem",1,{"item":24,"name":25,"@type":21,"position":26},"https://docshare.wps.com/document/","Document",2,{"item":28,"name":29,"@type":21,"position":30},"https://docshare.wps.com/document/healthcare/","Healthcare",3,{"item":32,"name":10,"@type":21,"position":33},"https://docshare.wps.com/document/standardizing-the-pathologic-assessment-of-her2-ultralow-breast-cancer-insights-from-a-national-italian-project/373965/",4,{"url":32,"name":10,"@type":35,"image":36,"author":41,"headline":10,"publisher":44,"fileFormat":47,"inLanguage":8,"description":12,"dateModified":48,"datePublished":49,"encodingFormat":47,"isAccessibleForFree":50,"interactionStatistic":51},"DigitalDocument",{"url":37,"@type":38,"width":39,"height":40},"https://docshare.wps.com/thumbnails/standardizing-the-pathologic-assessment-of-her2-ultralow-breast-cancer-insights-from-a-national-italian-project/373965.png","ImageObject",300,407,{"name":42,"@type":43},"MrHarris58","Person",{"url":19,"name":45,"@type":46},"DocShare","Organization","application/pdf","2026-11-01","2026-09-23",true,{"@type":52,"interactionType":53,"userInteractionCount":55},"InteractionCounter",{"@type":54},"ViewAction",10,{"@type":57,"mainEntity":58},"FAQPage",[59,65,69,73],{"name":60,"@type":61,"acceptedAnswer":62},"Why was standardization needed for HER2-(ultra)low breast cancer assessment?","Question",{"text":63,"@type":64},"Because multi-tier HER2 classification based on IHC introduces sensitivity to pre-analytical and analytical factors, making accurate identification at the lowest expression range challenging.","Answer",{"name":66,"@type":61,"acceptedAnswer":67},"How was the national Italian project conducted?",{"text":68,"@type":64},"A total of 121 pathologists completed an online survey, scored eight HER2-(ultra)low IHC whole-slide images, and joined on-site meetings to discuss results and evaluate additional challenging WSIs.",{"name":70,"@type":61,"acceptedAnswer":71},"What were the main findings on agreement with the expert panel?",{"text":72,"@type":64},"Overall agreement was substantial (69%), with higher agreement in the online phase than the on-site phase. Discordances were most common in the on-site cohort and within the HER2 0+/ultralow spectrum.",{"name":74,"@type":61,"acceptedAnswer":75},"What does the study conclude about clinical practice?",{"text":76,"@type":64},"Accurate classification of HER2-(ultra)low breast cancers remains complex, and variability in difficult cases supports the need for standardized assessment procedures.","https://schema.org",{"og:url":32,"og:type":79,"og:title":10,"og:site_name":45,"og:description":12},"article",{"robots":81,"canonical":32},"index,follow",{"doc_id":83,"site_id":7},373965,1790926841,{"code":4,"msg":86,"data":87},"success",[88,92,96,100,105,110,114,119,124,127,130],{"id":22,"doc_module":4,"doc_module_name":25,"category_name":89,"show_sort_weight":90,"slug":91},"Story & Novel",90,"story-novel",{"id":26,"doc_module":4,"doc_module_name":25,"category_name":93,"show_sort_weight":94,"slug":95},"Literature",80,"literature",{"id":33,"doc_module":4,"doc_module_name":25,"category_name":97,"show_sort_weight":98,"slug":99},"Exam",70,"exam",{"id":101,"doc_module":4,"doc_module_name":25,"category_name":102,"show_sort_weight":103,"slug":104},5,"Comic",60,"comic",{"id":106,"doc_module":4,"doc_module_name":25,"category_name":107,"show_sort_weight":108,"slug":109},6,"Technology",50,"technology",{"id":111,"doc_module":4,"doc_module_name":25,"category_name":29,"show_sort_weight":112,"slug":113},7,40,"healthcare",{"id":115,"doc_module":4,"doc_module_name":25,"category_name":116,"show_sort_weight":117,"slug":118},8,"Research & Report",30,"research-report",{"id":120,"doc_module":4,"doc_module_name":25,"category_name":121,"show_sort_weight":122,"slug":123},9,"Religion & Spirituality",20,"religion-spirituality",{"id":122,"doc_module":4,"doc_module_name":25,"category_name":125,"show_sort_weight":122,"slug":126},"World Cup","world-cup",{"id":55,"doc_module":4,"doc_module_name":25,"category_name":128,"show_sort_weight":55,"slug":129},"Lifestyle","lifestyle",{"id":131,"doc_module":4,"doc_module_name":25,"category_name":132,"show_sort_weight":101,"slug":133},19,"General","general",{"code":4,"msg":86,"data":135},{"doc_id":83,"user_id":136,"nickname":42,"user_avatar":137,"doc_module":4,"category_id":111,"category_name":29,"doc_title":10,"doc_description":12,"doc_content":138,"file_id":139,"file_url":140,"file_type":141,"file_size":142,"view_count":55,"is_deleted":4,"is_public":22,"is_downloadable":22,"audit_status":22,"page_count":143,"language":144,"language_code":8,"site_id":7,"html_lang":8,"table_of_contents":145,"faqs":146,"seo_title":147,"seo_description":12,"update_tm":148,"read_time":117},687212988360,"https://ap-avatar.wpscdn.com/davatar_276721f389ce27ea32af1340a28f341c","PATHOLOGICA 2025;117:559-570 DOI: 10.32074/1591-951X-1565  \nReceived: July 31, 2025  \nAccepted: October 28, 2025  \nCorrespondence  \nCristian Scatena  \nE-mail: [cristian.scatena@unipi.it](cristian.scatena@unipi.it)[ ](cristian.scatena@unipi.it)Isabella Castellano  \nE-mail: isabella.castellano@unito. it  \nHow to cite this article: Cerbelli B, Marletta S, Amato M, et al. Standardizing the pathologic assessment of HER2-(ultra)low breast cancer: insights from a national Italian project. Pathologica 2025;117:559-570 . [https://doi](https://doi). org/10.32074/1591-951X-1565  \n© Copyright by Società Italiana di Anatomia Patologica e Citopatologia Diagnostica, Divisione Italiana della International Academy of Pathology  \n OPEN ACCESS  \nThis is an open access journal distributed in accordance with the CC-BY-NC-ND (Creative Commons AttributionNonCommercial-NoDerivatives 4.0 International) license: the work can be used by mentioning the author and the license, but only for non-commercial purposes and only in the original version. For further information: [https://creativecommons](https://creativecommons). org/licenses/by-nc-nd/4.0/deed.en  \nOriginal article  \nStandardizing the pathologic assessment of HER2-(ultra)low breast cancer: insights from a national Italian project  \nBruna Cerbelli\\#, Stefano Marletta2,3\\#, Michelina Amato4 , Michela Campora5 , Leopoldo Costarelli 4 , Antonio Cossu6 , Veronica Errigo7 , Gerardo Ferrara8 , Maria Pia Foschini9 , Renato Franco10 , Nicola Fusco11 , Antonio Marchetti12 , Mauro G Mastropasqua13 , Enrico Orvieto14 , Francesca Pietribiasi15 , Moira Ragazzi16 , Antonio Rizzo17 , Alfredo Santinelli18 , Fabrizio Zanconati19 ,  \nGiulia d’Amati1 , Cristian Scatena20 , Isabella Castellano21 and GIPaM working group  \n1 Department of Radiology, Oncology and Pathology, Sapienza, University of Rome, Rome, Italy; 2 Department of Biomedical Sciences, Humanitas University, Pieve Emanuele (Milan), Italy; 3 Division of Pathology, Humanitas Istituto Clinico Catanese, Catania, Italy; 4 Department of Pathology, San Giovanni-Addolorata Hospital, Rome Italy; 5 Department of Pathology, Santa Chiara Hospital, APSS Trento, Trento, Italy; 6 Department of Medical, Surgical and Experimental Sciences, University of Sassari, Sassari, Italy; 7 Anatomical Pathology Unit, Ospedale San Paolo, Savona, Italy; 8 Pathological Anatomy and Cytopathology Unit, Istituto Nazionale Tumori, IRCCS Fondazione G. Pascale, Naples, Italy; 9 Department of Biomedical and Neuromotor Sciences, University of Bologna, Anatomic Pathology at Bellaria Hospital, Bologna, Italy; 10 Department of Mental and Physical Health and Preventive Medicine, Pathology Unit, University of Campania “Luigi Vanvitelli”, Naples, Italy; 11 Division of Pathology, IEO, European Institute of Oncology IRCCS, Milan, Italy; Department of Oncology and HematoOncology, University of Milan, Milan, Italy; 12 Department of Medical, Oral and Biotechnological Sciences, Centre for Advanced Studies and Technology (CAST), University of Chieti, Chieti, Italy; 13 Department of Precision a14ndDeRegparteneramenttvfePMeathilcoinegy, and JULSSon8ianBerAicrea,aS, ScanhoBoorltoolMHicpiinetal,, UVincversnza,ityItaolfy;B1a5riDi“AvidioonMoroof Pa”t,hBaroloig,Iy,taly; Santa Croce Hospital, Moncalieri, Turin, Italy; 16 Pathology Unit, Arcispedale Santa Maria Nuova, Azienda Unità Sanitaria Locale-IRCCS di Reggio Emilia, Reggio Emilia, Italy; 17 Division of Pathology, Clinical Institute Humanitas Catania Cubba, Misterbianco (Catania), Italy; 18 Anatomic Pathology, Azienda Sanitaria Territorialedi Pesaro-Urbino, Pesaro, Italy; 19 Department of Medical, Surgical and Health Sciences, University of Trieste, Trieste, Italy; 20 Division of Pathology, Department of Translational Research and New Technologies in Medicine and Surgery, University of Pisa, Pisa, Italy; 21 Department of Medical Science, University of Turin, Turin, Italy \\#these authors are equally contributed  \nSummary  \nObjective. Novel therapies for HER2-(","cbCairriPjCMXvZ5","https://ap.wps.com/l/cbCairriPjCMXvZ5","pdf",954395,12,"English","# Summary\n## Objective\n## Material and methods\n## Results\n## Conclusions","[{\"question\":\"Why was standardization needed for HER2-(ultra)low breast cancer assessment?\",\"answer\":\"Because multi-tier HER2 classification based on IHC introduces sensitivity to pre-analytical and analytical factors, making accurate identification at the lowest expression range challenging.\"},{\"question\":\"How was the national Italian project conducted?\",\"answer\":\"A total of 121 pathologists completed an online survey, scored eight HER2-(ultra)low IHC whole-slide images, and joined on-site meetings to discuss results and evaluate additional challenging WSIs.\"},{\"question\":\"What were the main findings on agreement with the expert panel?\",\"answer\":\"Overall agreement was substantial (69%), with higher agreement in the online phase than the on-site phase. Discordances were most common in the on-site cohort and within the HER2 0+/ultralow spectrum.\"},{\"question\":\"What does the study conclude about clinical practice?\",\"answer\":\"Accurate classification of HER2-(ultra)low breast cancers remains complex, and variability in difficult cases supports the need for standardized assessment procedures.\"}]","Standardizing the pathologic assessment of HER2-(ultra)low breast cancer - insights from a national Italian project | PDF",1790200916]