[{"data":1,"prerenderedAt":-1},["ShallowReactive",2],{"detail-sidebar-cat-0-en-105":3,"doc-seo-331865-105":59,"doc-detail-331865-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","management-of-neuroendocrine-breast-carcinoma-nebc-review-of-literature","Management of Neuroendocrine Breast Carcinoma (NEBC) - Review of Literature","","Extra pulmonary high-grade poorly differentiated neuroendocrine carcinomas (EP-NECs) are rare, and primary neuroendocrine carcinoma of the breast (NEBC) is even rarer, often under 0.1% of all breast cancers. Owing to low incidence, heterogeneous histology, and inconsistent immunohistochemical (IHC) diagnostic criteria, NEBC is frequently misdiagnosed and its management does not reliably follow standard breast cancer guidelines. This review synthesizes current evidence on histopathology, IHC features, treatment approaches, and prognosis, emphasizing the diagnostic value of proper IHC studies.",{"@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/management-of-neuroendocrine-breast-carcinoma-nebc-review-of-literature/331865/",{"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/management-of-neuroendocrine-breast-carcinoma-nebc-review-of-literature/331865.png","ImageObject",300,407,{"name":92,"@type":93},"Patrick","Person",{"url":74,"name":95,"@type":96},"DocShare","Organization","application/pdf","2026-10-29","2026-09-21",true,{"@type":102,"interactionType":103,"userInteractionCount":44},"InteractionCounter",{"@type":104},"ViewAction",{"@type":106,"mainEntity":107},"FAQPage",[108,114,118],{"name":109,"@type":110,"acceptedAnswer":111},"Why is primary neuroendocrine carcinoma of the breast (NEBC) often misdiagnosed?","Question",{"text":112,"@type":113},"NEBC is extremely rare and lacks uniform histological and immunohistochemical (IHC) diagnostic criteria. As a result, IHC neuroendocrine markers may not be routinely used, leading to diagnostic confusion with other breast cancer types.","Answer",{"name":115,"@type":110,"acceptedAnswer":116},"How have WHO classifications for breast neuroendocrine neoplasms changed?",{"text":117,"@type":113},"The WHO 2003 classification defined NECB using neuroendocrine marker positivity in more than 50% of tumor cells. In 2012, the 50% cutoff was removed and categories were reorganized, and in 2019 breast NENs were reclassified into well-differentiated NET or poorly differentiated NEBC, including small cell and large cell NEC.",{"name":119,"@type":110,"acceptedAnswer":120},"What clinical and biological features are commonly associated with NEBC?",{"text":121,"@type":113},"The typical median age is reported around 60–70 years with female predominance. Specific endocrine symptoms are not consistently notable, but hormone receptor (ER and PR) expression is typically observed, and endocrine syndromes may occur in limited reports.","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},331865,1790124134,{"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":44,"is_deleted":4,"is_public":8,"is_downloadable":8,"audit_status":8,"page_count":34,"language":139,"language_code":63,"site_id":62,"html_lang":63,"table_of_contents":140,"faqs":141,"seo_title":142,"seo_description":67,"update_tm":143,"read_time":144},549758146520,"https://ap-avatar.wpscdn.com/avatar/80002397d8c0411e94?_k=1775819394049821470","Edited by:  \nMauro Cives, University of Bari Aldo Moro, Italy  \nReviewed by: Eleonora Pelle,  \nMoffitt Cancer Center, United States Eleonora Lauricella,  \nAzienda Ospedaliero Universitaria Consorziale Policlinico di Bari, Italy  \n*Correspondence  \nA. Mohamed,  [amr.mohamed@uhhospitals.org](amr.mohamed@uhhospitals.org)  \nReceived: 25 September 2023  \nAccepted: 15 January 2024  \nPublished: 09 February 2024  \nCitation: Mohamed A, Zeidalkilani J, Asa SL, Trybula M and Montero AJ (2024) Management of Neuroendocrine Breast Carcinoma (NEBC): Review of Literature.  \nOncol. Rev. 18:12114.  \ndoi: 10.3389/or.2024.12114  \nManagement of Neuroendocrine Breast Carcinoma (NEBC): Review of Literature  \nA. Mohamed 1 *, J. Zeidalkilani 2, S. L. Asa 3, M. Trybula 1 and Alberto J. Montero 1  \n1Division of Hematology and Medical Oncology, University Hospitals Seidman Cancer Center, Cleveland, OH, United States, 2Department of Medicine, University Hospitals Seidman Cancer Center, Cleveland, OH, United States, 3Department of Pathology, University Hospitals Seidman Cancer Center, Case Comprehensive Cancer Center, Case Western Reserve University, Cleveland, OH, United States  \nExtra pulmonary high-grade poorly differentiated neuroendocrine carcinomas (EP-NECs) are rare tumors that usually arise in the gastrointestinal and genitourinary tracts. Primary neuroendocrine carcinoma of the breast (NEBC) is extremely rare, representing less than 0. 1% of all breast cancers and less than 1% of neuroendocrine neoplasms. Consequently, they can be misdiagnosed as other types of breast cancer, however, proper immunohistochemical (IHC) studies can assist with making the correct diagnosis. Management of NEBC can be challenging given the paucity of evidence-based literature and should not routinely follow the therapeutic guidelines of other breast cancers. In this article, we review the current literature regarding the management of NEBC.  \nKeywords: management, breast, neuroendocrine, carcinoma, review  \nINTRODUCTION  \nAlthough neuroendocrine cells are widely distributed throughout the human body, neuroendocrine neoplasms (NENs) are uncommon. There are multiple definitions, classifications, and nomenclatures that have been used for NENs. However, over the past two decades, NEN nomenclature has evolved to divide them into two major categories: well-differentiated neuroendocrine tumors (NETs) and poorly differentiated neuroendocrine carcinomas (NECs) . Primary NECs of the breast are rare tumors (NEBC), with an incidence rate of only 0.3%–0.5%, accounting for 0.1%–5% of breast cancers and less than 1% of neuroendocrine neoplasms [1] . The difference in reported prevalence rates is due to the lack of uniform histological and immunohistochemical (IHC) diagnostic criteria and usually the IHC neuroendocrine markers are not routinely used in the diagnosis of breast cancer. The first case of neuroendocrine differentiation in a breast carcinoma was observed in 1963 by Feyrter and Hartmann. It was not until 1977 when the first case of primary NEBC was reported by Cubila and Woodruff who provided clinical and histological classification for this rare subtype of breast cancer [2, 3] . Because of their low incidence, current knowledge of this tumor is scarce and based on a limited number of anecdotal case reports or small retrospective series. Therefore, their definition, pathological diagnosis, and management remain controversial in the current literature. In this review, we summarized the current evidence about histopathological, immunohistochemical features, as well as management and prognosis of NEBC.  \nHISTOPATHOLOGY  \nThe 2003 World Health Organization (WHO) breast cancer classification defined NECB as an independent histological entity with immunoreactivity for neuroendocrine markers (chromogranin, synaptophysin, INSM1) in more than 50% of the tumor cells. This WHO classification excluded from their definition breast carcinomas with focal neuroendocrine expression [4, 5] . The classifi","cbCaishRvRL3QYYj","https://ap.wps.com/l/cbCaishRvRL3QYYj","pdf",1434171,"English","# Introduction\n## Histopathology\n## Clinical Presentation","[{\"question\":\"Why is primary neuroendocrine carcinoma of the breast (NEBC) often misdiagnosed?\",\"answer\":\"NEBC is extremely rare and lacks uniform histological and immunohistochemical (IHC) diagnostic criteria. As a result, IHC neuroendocrine markers may not be routinely used, leading to diagnostic confusion with other breast cancer types.\"},{\"question\":\"How have WHO classifications for breast neuroendocrine neoplasms changed?\",\"answer\":\"The WHO 2003 classification defined NECB using neuroendocrine marker positivity in more than 50% of tumor cells. In 2012, the 50% cutoff was removed and categories were reorganized, and in 2019 breast NENs were reclassified into well-differentiated NET or poorly differentiated NEBC, including small cell and large cell NEC.\"},{\"question\":\"What clinical and biological features are commonly associated with NEBC?\",\"answer\":\"The typical median age is reported around 60–70 years with female predominance. Specific endocrine symptoms are not consistently notable, but hormone receptor (ER and PR) expression is typically observed, and endocrine syndromes may occur in limited reports.\"}]","Management of Neuroendocrine Breast Carcinoma (NEBC) - Review of Literature | PDF",1789995541,18]