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Summarizes key formation mechanisms, including aberrant DNA damage repair and chromosomal rearrangements, and links ecDNA to oncogene expression, tumor heterogeneity, and immune evasion. Reports subtype-dependent ecDNA distribution, associations with invasive and triple-negative disease, and implications for prognosis and resistance. Highlights detection approaches and the biomarker potential for liquid biopsy, concluding with prospects for ecDNA-targeted therapy integrated with immunotherapy despite ongoing challenges.",{"@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/research-advances-of-extrachromosomal-circular-dna-in-breast-cancer/374824/",{"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/research-advances-of-extrachromosomal-circular-dna-in-breast-cancer/374824.png","ImageObject",300,407,{"name":92,"@type":93},"Kurz","Person",{"url":74,"name":95,"@type":96},"DocShare","Organization","application/pdf","2026-10-29","2026-09-23",true,{"@type":102,"interactionType":103,"userInteractionCount":39},"InteractionCounter",{"@type":104},"ViewAction",{"@type":106,"mainEntity":107},"FAQPage",[108,114,118],{"name":109,"@type":110,"acceptedAnswer":111},"What role does ecDNA play in breast cancer initiation, progression, diagnosis, and treatment?","Question",{"text":112,"@type":113},"ecDNA is described as a distinct form of DNA that is critically involved in the initiation, progression, diagnosis, and treatment of breast cancer. It contributes to gene regulation and tumor evolution through its biological behaviors.","Answer",{"name":115,"@type":110,"acceptedAnswer":116},"How is ecDNA formed in breast cancer cells?",{"text":117,"@type":113},"ecDNA formation is attributed to intricate cellular processes, especially error-prone repair of DNA double-strand breaks. Pathways such as NHEJ and MMEJ can circularize chromosomal fragments to generate ecDNA.",{"name":119,"@type":110,"acceptedAnswer":120},"Why is ecDNA considered a biomarker and therapeutic target?",{"text":121,"@type":113},"Epidemiological evidence links ecDNA presence to poor prognosis and treatment resistance, and its detectability in plasma supports liquid biopsy use. The review also emphasizes development of ecDNA-targeted therapies and integration with immunotherapy as promising treatment avenues.","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},374824,1790739129,{"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":39,"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},2336478945635,"https://ap-avatar.wpscdn.com/davatar_6f874abed73319feea01a86fa6f0fab8","Cancer Medicine  \n|  REVIEW  OPEN ACCESS \u003Cbr>Research Advances of Extrachromosomal Circular DNA in Breast Cancer\u003Cbr>Xiaodan Zhu | Yiyang Qian  | Quan Tang | Jiahui Li | Yuqing Geng | Shixia Gong | Chunhui Jin \u003Cbr>Wuxi Hospital Affiliated to Nanjing University of Chinese Medicine, Wuxi, China\u003Cbr>Correspondence: Shixia Gong ([71065824@qq.com](71065824@qq.com)) | Chunhui Jin ([wxzy013@njucm.edu.cn](wxzy013@njucm.edu.cn))\u003Cbr>Received: 30 June 2025 | Revised: 17 September 2025 | Accepted: 19 September 2025\u003Cbr>Funding: This study was supported by the National Natural Science Foundation of China (no. 82505450); the Top Talent Support Program for young and middle-aged people of Wuxi Health Committee (HB2023067); the Project supported by the Natural Science Foundation of Jiangsu Province, China (no. BK20240309); and the Natural Science Foundation of Nanjing University of Chinese Medicine (XZR2023095) .\u003Cbr>Keywords: biological function | biomarker | breast cancer | extrachromosomal circular DNA (ecDNA) | targeted therapy | therapeutic strategies |  |\n| --- | --- |\n| ABSTRACT\u003Cbr>Background: This article presents an extensive review of the advancements in research concerning extrachromosomal circular DNA (ecDNA) within the context of breast cancer. As a distinct form of DNA, ecDNA is critically involved in the initiation, progression, diagnosis, and treatment of breast cancer.\u003Cbr>Methods: The article provides a comprehensive analysis of the mechanisms underlying the formation of ecDNA, highlighting factors such as aberrant DNA damage repair and chromosomal rearrangements. It further examines the biological roles of ecDNA in augmenting oncogene expression, fostering tumor heterogeneity, and facilitating immune evasion.\u003Cbr>Results: Epidemiological studies indicate significant variability in the distribution of ecDNA across different breast cancer subtypes, with a notable association with invasive subtypes, such as triple-negative breast cancer. The presence of ecDNA is linked to poor prognosis and treatment resistance in patients. Current detection technologies for ecDNA include molecular biology and imaging techniques, and its detectability in plasma underscores its potential as a biomarker for liquid biopsy.\u003Cbr>Conclusions: The development of ecDNA-targeted therapies and their integration with immunotherapy strategies offers promising new avenues for breast cancer treatment. Despite challenges such as incomplete elucidation of mechanisms, standardization of detection methods, and ethical considerations, ecDNA remains a valuable biomarker and therapeutic target in breast cancer. Future research is anticipated to advance its clinical transformation and application in individualized treatment. |  |\n| 1 | Overview of Extrachromosomal Circular DNA | the functional subclass of extrachromosomal circular DNA (ec- |\n| Extrachromosomal DNA (ecDNA) specifically refers to large extrachromosomal particles existing in cancer cells and belongs to | cDNA) [1]. It can be detected in approximately 17% of cancers [2] . ecDNA is relatively large in size, reaching several million base pairs (at the Mb level) [3], and it maintains a relatively stable |\n| Abbreviations: AI, artificial intelligence; AUC, area under the curve; CCND1, cyclin D1; Circle-seq, circular DNA sequencing; CRISPR, clustered regularly interspaced short palindromic repeats; dCas9, catalytically “dead” Cas9; DDR, DNA damage response; DMs, double minute chromosomes; DSB, double-strand break; eccDNA, extrachromosomal circular DNA; eccMIR, extrachromosomal circular DNA carrying miRNA; ecDNA, extrachromosomal DNA; EGFR, epidermal growth factor receptor; ER, estrogen receptor; ERBB2, erythroblastic leukemia viral oncogene homolog 2 (HER2); FISH, fluorescence in situ hybridization; gRNA, guide RNA; HSGs, hotspot genes; HU, hydroxyurea; LADs, lamina-associated domains; ML, Machine Learning; MMEJ, microhomology-mediated end joining; MYC, MYCproto-oncogene; NHEJ, nonhomologous end joining; ORC, origi","cbCaimMWwrf9hQIK","https://ap.wps.com/l/cbCaimMWwrf9hQIK","pdf",955459,13,"English","# Overview of Extrachromosomal Circular DNA\n## Formation Mechanisms and Biological Functions of ecDNA in Breast Cancer","[{\"question\":\"What role does ecDNA play in breast cancer initiation, progression, diagnosis, and treatment?\",\"answer\":\"ecDNA is described as a distinct form of DNA that is critically involved in the initiation, progression, diagnosis, and treatment of breast cancer. It contributes to gene regulation and tumor evolution through its biological behaviors.\"},{\"question\":\"How is ecDNA formed in breast cancer cells?\",\"answer\":\"ecDNA formation is attributed to intricate cellular processes, especially error-prone repair of DNA double-strand breaks. Pathways such as NHEJ and MMEJ can circularize chromosomal fragments to generate ecDNA.\"},{\"question\":\"Why is ecDNA considered a biomarker and therapeutic target?\",\"answer\":\"Epidemiological evidence links ecDNA presence to poor prognosis and treatment resistance, and its detectability in plasma supports liquid biopsy use. The review also emphasizes development of ecDNA-targeted therapies and integration with immunotherapy as promising treatment avenues.\"}]","Research Advances of Extrachromosomal Circular DNA in Breast Cancer | PDF",1790202502,33]