[{"data":1,"prerenderedAt":-1},["ShallowReactive",2],{"doc-seo-361066-105":3,"detail-sidebar-cat-0-en-105":81,"doc-detail-361066-en":130},{"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":74,"head_meta":76,"extra_data":78,"updated_unix":80},105,"en","somatic-brca-alterations-in-breast-cancer-are-associated-with-distinct-biological-and-clinical-patterns-according-to-germline-brca-status","Somatic BRCA alterations in breast cancer are associated with distinct biological and clinical patterns according to germline BRCA status","","Comprehensive genomic profiling identifies BRCA alterations in breast cancer, yet the clinical meaning of somatic BRCA changes remains uncertain. This study analyzed 2,978 breast cancer cases with matched germline and somatic BRCA status from a cancer genomics database, grouping tumors by g+/s+, g+/s−, g−/s+, and g−/s−. Results showed limited germline–somatic concordance, with somatic BRCA alterations more common in metastatic lesions. Genomic patterns differed by group, including HRD features, and clinical outcomes varied in ER+ / HER2− disease, while TNBC immune checkpoint inhibitor results were not linked to BRCA status.",{"@graph":14,"@context":73},[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/somatic-brca-alterations-in-breast-cancer-are-associated-with-distinct-biological-and-clinical-patterns-according-to-germline-brca-status/361066/",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/somatic-brca-alterations-in-breast-cancer-are-associated-with-distinct-biological-and-clinical-patterns-according-to-germline-brca-status/361066.png","ImageObject",300,407,{"name":42,"@type":43},"awa","Person",{"url":19,"name":45,"@type":46},"DocShare","Organization","application/pdf","2026-10-23","2026-09-23",true,{"@type":52,"interactionType":53,"userInteractionCount":55},"InteractionCounter",{"@type":54},"ViewAction",8,{"@type":57,"mainEntity":58},"FAQPage",[59,65,69],{"name":60,"@type":61,"acceptedAnswer":62},"How were breast cancer patients grouped in this study?","Question",{"text":63,"@type":64},"Patients were categorized into four groups based on matched germline and somatic BRCA status: g+/s+, g+/s−, g−/s+, and g−/s−.","Answer",{"name":66,"@type":61,"acceptedAnswer":67},"What did the study find about concordance between germline and somatic BRCA status?",{"text":68,"@type":64},"Concordance between germline and somatic BRCA status was limited, and g−/s+ tumors were more prevalent than g+/s+ tumors.",{"name":70,"@type":61,"acceptedAnswer":71},"Did BRCA alteration groups relate to immune checkpoint inhibitor outcomes in triple-negative breast cancer?",{"text":72,"@type":64},"In triple-negative breast cancer, immune checkpoint inhibitor outcomes were not associated with BRCA status.","https://schema.org",{"og:url":32,"og:type":75,"og:title":10,"og:site_name":45,"og:description":12},"article",{"robots":77,"canonical":32},"index,follow",{"doc_id":79,"site_id":7},361066,1790756658,{"code":4,"msg":82,"data":83},"success",[84,88,92,96,101,106,110,114,119,122,126],{"id":22,"doc_module":4,"doc_module_name":25,"category_name":85,"show_sort_weight":86,"slug":87},"Story & Novel",90,"story-novel",{"id":26,"doc_module":4,"doc_module_name":25,"category_name":89,"show_sort_weight":90,"slug":91},"Literature",80,"literature",{"id":33,"doc_module":4,"doc_module_name":25,"category_name":93,"show_sort_weight":94,"slug":95},"Exam",70,"exam",{"id":97,"doc_module":4,"doc_module_name":25,"category_name":98,"show_sort_weight":99,"slug":100},5,"Comic",60,"comic",{"id":102,"doc_module":4,"doc_module_name":25,"category_name":103,"show_sort_weight":104,"slug":105},6,"Technology",50,"technology",{"id":107,"doc_module":4,"doc_module_name":25,"category_name":29,"show_sort_weight":108,"slug":109},7,40,"healthcare",{"id":55,"doc_module":4,"doc_module_name":25,"category_name":111,"show_sort_weight":112,"slug":113},"Research & Report",30,"research-report",{"id":115,"doc_module":4,"doc_module_name":25,"category_name":116,"show_sort_weight":117,"slug":118},9,"Religion & Spirituality",20,"religion-spirituality",{"id":117,"doc_module":4,"doc_module_name":25,"category_name":120,"show_sort_weight":117,"slug":121},"World Cup","world-cup",{"id":123,"doc_module":4,"doc_module_name":25,"category_name":124,"show_sort_weight":123,"slug":125},10,"Lifestyle","lifestyle",{"id":127,"doc_module":4,"doc_module_name":25,"category_name":128,"show_sort_weight":97,"slug":129},19,"General","general",{"code":4,"msg":82,"data":131},{"doc_id":79,"user_id":132,"nickname":42,"user_avatar":133,"doc_module":4,"category_id":107,"category_name":29,"doc_title":10,"doc_description":12,"doc_content":134,"file_id":135,"file_url":136,"file_type":137,"file_size":138,"view_count":55,"is_deleted":4,"is_public":22,"is_downloadable":22,"audit_status":22,"page_count":123,"language":139,"language_code":8,"site_id":7,"html_lang":8,"table_of_contents":140,"faqs":141,"seo_title":142,"seo_description":12,"update_tm":143,"read_time":144},3985747858093,"https://ap-avatar.wpscdn.com/davatar_3d24733baf745e90a7e4bdd5f77d97b2","ORIGINAL ARTICLE  \nSomatic BRCA alterations in breast cancer are associated with distinct biological and clinical patterns according to germline BRCA status  \nM. Oshi1 , 2 ∗, K. Kawashima1 , 2, M. Sugimori3, A. Yamada2, Z. Shah4, K. Onel4 , 5, I. Endo2 & K. Takabe1 , 2 ,4 , 5 , 6 , 7 , 8  \n1Department of Surgical Oncology, Roswell Park Comprehensive Cancer Center, Buffalo, USA; 2Department of Gastroenterological Surgery, Yokohama City University Graduate School of Medicine, Yokohama; 3Division of Cancer Genome Medicine, Yokohama City University Medical Center, Yokohama, Japan; 4Department of Medicine, Roswell Park Comprehensive Cancer Center, Buffalo; 5Department of Cancer Prevention & Control, Roswell Park Comprehensive Cancer Center, Buffalo; 6Department of Surgery, Jacobs School of Medicine and Biomedical Sciences, State University of New York, Buffalo, USA; 7Department of Surgery, Niigata University Graduate School of Medical and Dental Sciences, Niigata; 8Department of Breast Surgery, Fukushima Medical University, Fukushima, Japan  \nAvailable online xxx  \nBackground: Comprehensive genomic profiling increasingly identifies BRCA alterations in breast cancer (BC) . While germline BRCA mutations are well established as biologically and clinically relevant, the significance of somatic BRCA alterations remains unclear. We hypothesized that the implications of BRCA alterations may differ according to germline BRCA alterations.  \nPatients and methods: Among 5411 BC cases registered in the Center for Cancer Genomics and Advanced Therapeutics database, we analyzed 2978 BC cases with available germline (g) and somatic (s) BRCA status. Patients were categorized into four groups (g+/s+, g+/s − , g − /s+, and g − /s − ) . Mutational landscapes, homologous recombination deficiency (HRD)-related alterations, specimen origin, and time to treatment discontinuation (TTD) were evaluated, focusing on estrogen receptor (ER)-positive/HER2-negative and triple-negative breast cancer (TNBC) . Results: g − /s+ tumors were more prevalent than g+/s+ tumors, and concordance between germline and somatic BRCA status was limited. Somatic BRCA alterations were more frequently detected in metastatic lesions and were more frequently observed in metastatic specimens. Genomically, g − /s+ tumors were enriched for oncogenic signaling mutations, including PIK3CA and TP53, whereas g+/s+ tumors showed HRD-related features dominated by BRCA alterations. Non-BRCA HRD-related alterations were most frequent in g − /s+ tumors (52%; P = 0.004) . In ERpositive/HER2-negative BC, germline BRCA positivity was associated with shorter cyclin-dependent kinase 4 and 6 inhibitor TTD, and g+/s+ status remained independently associated with shorter TTD (hazard ratio 1.3, P \u003C 0.001), whereas g − /s+ tumors were comparable with g − /s − tumors. In contrast, g − /s+ tumors showed TTD comparable with g − /s − tumors. In TNBC, immune checkpoint inhibitor outcomes were not associated with BRCA status. Conclusions: BRCA alteration groups defined by combined germline and somatic status showed distinct genomic and clinical patterns in BC. Somatic BRCA alterations should not be interpreted in isolation and require integration with germline status and broader genomic context.  \nKey words: breast cancer, cdk4/6 inhibitors, comprehensive genomic profiling, germline BRCA, somatic BRCA, tumor evolution  \nINTRODUCTION  \nBreast cancer (BC) is the most common malignancy among women worldwide,1 and defects in homologous recombination repair (HRR) represent one of the most clinically actionable genomic vulnerabilities. Germline pathogenic variants in BRCA1 and BRCA2 are well-established drivers of  \n*Correspondence to: Dr Masanori Oshi, Department of Gastroenterological Surgery, Yokohama City University Graduate School of Medicine, 3-9 Fukuura, Kanazawa-ku, Yokohama, Kanagawa 236-0004, Japan  \nE-mail: [oshi.mas.wc@yokohama-cu.ac.jp](oshi.mas.wc@yokohama-cu.ac.jp) (M. Oshi).  \n2059-7029/© 2026 The Au","cbCaidSkWdQL3osZ","https://ap.wps.com/l/cbCaidSkWdQL3osZ","pdf",1540793,"English","# Background\n# Patients and methods\n# Results\n# Conclusions\n# Introduction","[{\"question\":\"How were breast cancer patients grouped in this study?\",\"answer\":\"Patients were categorized into four groups based on matched germline and somatic BRCA status: g+/s+, g+/s−, g−/s+, and g−/s−.\"},{\"question\":\"What did the study find about concordance between germline and somatic BRCA status?\",\"answer\":\"Concordance between germline and somatic BRCA status was limited, and g−/s+ tumors were more prevalent than g+/s+ tumors.\"},{\"question\":\"Did BRCA alteration groups relate to immune checkpoint inhibitor outcomes in triple-negative breast cancer?\",\"answer\":\"In triple-negative breast cancer, immune checkpoint inhibitor outcomes were not associated with BRCA status.\"}]","Somatic BRCA alterations in breast cancer are associated with distinct biological and clinical patterns according to germline BRCA status | PDF",1790142995,25]