[{"data":1,"prerenderedAt":-1},["ShallowReactive",2],{"detail-sidebar-cat-0-en-105":3,"doc-seo-354466-105":59,"doc-detail-354466-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","breast-cancer-phenotypes-in-carriers-of-pathogenic-pot1-variants","Breast cancer phenotypes in carriers of pathogenic POT1 variants","","Germline pathogenic variants (PVs) in POT1, a shelterin complex gene, are linked to tumor predisposition, mainly melanoma and several hematologic and solid malignancies, yet breast cancer (BC) risk has not been clearly elevated. This study analyzes BC occurrence and clinicopathologic features in 29 female POT1 PV heterozygotes, including genetic, treatment, and outcome data. Thirty-nine percent of tumors were stage 0/I, estrogen receptor positivity predominated, and follow-up showed no BC-related mortality, suggesting consideration of enhanced surveillance.",{"@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":40,"@type":76,"position":81},"https://docshare.wps.com/document/research-report/",3,{"item":83,"name":65,"@type":76,"position":19},"https://docshare.wps.com/document/breast-cancer-phenotypes-in-carriers-of-pathogenic-pot1-variants/354466/",{"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/breast-cancer-phenotypes-in-carriers-of-pathogenic-pot1-variants/354466.png","ImageObject",300,407,{"name":92,"@type":93},"Guten tag","Person",{"url":74,"name":95,"@type":96},"DocShare","Organization","application/pdf","2026-09-23","2026-09-22",true,{"@type":102,"interactionType":103,"userInteractionCount":14},"InteractionCounter",{"@type":104},"ViewAction",{"@type":106,"mainEntity":107},"FAQPage",[108,114,118],{"name":109,"@type":110,"acceptedAnswer":111},"What is the main goal of this study on POT1 carriers?","Question",{"text":112,"@type":113},"To evaluate breast cancer occurrence and characterize genetic, clinical, pathologic, treatment, and outcome features in female heterozygotes with pathogenic POT1 variants.","Answer",{"name":115,"@type":110,"acceptedAnswer":116},"Which breast cancer subtypes and biomarkers were observed in the cohort?",{"text":117,"@type":113},"Invasive ductal carcinoma was most common; all primary tumors with available data were estrogen receptor positive, one was HER2-enriched, and no triple-negative cancers were observed.",{"name":119,"@type":110,"acceptedAnswer":120},"How did breast cancer outcomes look during follow-up?",{"text":121,"@type":113},"After a median follow-up of 110 months, three second breast cancer events occurred and there was no breast-cancer-related mortality reported.","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},354466,1790171061,{"code":4,"msg":5,"data":131},{"doc_id":128,"user_id":132,"nickname":92,"user_avatar":133,"doc_module":4,"category_id":39,"category_name":40,"doc_title":65,"doc_description":67,"doc_content":134,"file_id":135,"file_url":136,"file_type":137,"file_size":138,"view_count":14,"is_deleted":4,"is_public":8,"is_downloadable":8,"audit_status":8,"page_count":29,"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},687212321768,"https://ap-avatar.wpscdn.com/avatar/a0010bdbe886d2fe77?x-image-process=image/resize,m_fixed,w_180,h_180&k=1789897067658708522","Familial Cancer (2026) 25:76  \n[https://doi.org/10.1007/s10689-026-00589-6](https://doi.org/10.1007/s10689-026-00589-6)  \nORIGINAL ARTICLE  \nBreast cancer phenotypes in carriers of pathogenic POT1 variants  \nTal Hadar1,2 · Aasem Abu Shtaya3 · Rinat Bernstein-Molho4,5 · Marina Eskin-Schwartz6,7 · Inbal Kedar8 · Tamar Peretz-Yablonsky2,9 · Shiri Shkedi-Rafid2,10 · Rinat Yerushalmi5,11 · Aviad Zick9,2 · Gili Reznick-Levi12 · Tanir Allweis1,2 · Yael Goldberg5,8  \nReceived: 18 April 2026 / Accepted: 25 June 2026 © The Author(s) 2026  \nAbstract  \nGermline pathogenic variants (PVs) in POT1, one of the shelterin complex genes, correlate with tumor predisposition, primarily with melanoma, hematologic malignancies, sarcoma, papillary thyroid carcinoma and glioma. Breast cancer (BC) risk has not been shown to be elevated. We analyzed BC occurrence and features in a cohort of 29 female PV heterozygotes, of whom 13/29 (45%) were diagnosed with BC. Data regarding genetic, clinical, pathologic, treatment, and outcome characteristics were extracted. Patients in our cohort harbored three different POT1 PVs; The c.233T >C Ashkenazi founder PV occurred in 11/13 (84.6%) . Median age at first BC diagnosis was 54 years (range 44–72); no patient was diagnosed before the age of 40. Pathological subtypes varied; invasive ductal carcinoma was the most common. All primary tumors were estrogen receptor positive; one was HER2-enriched; no triple-negative cancers were observed. Stage at diagnosis varied: 6 of 10 tumors with known staging were stage 0 or I, and one patient presented with metastatic disease. Treatment approaches were diverse as clinically appropriate. After a median follow-up of 110 months, three second BC events occurred, with no BC-related mortality. Personal and family history of other malignancies were frequent. This is the first dedicated report describing BC phenotypes in POT1 PV heterozygotes. Our findings suggest that enhanced BC surveillance may be warranted in this population. Larger cohorts are needed to further characterize the clinicopathological features of BC in POT1 carriers, to define lifetime BC risk and determine whether BC-specific screening recommendations should be established for this group.  \nKeywords POT1 · Hereditary breast cancer · Germline pathogenic variants · Telomeres  \n Tal Hadar[talh@hadassah.org.il](talh@hadassah.org.il)  \n1 Department of Breast Surgery, Hadassah Medical Center, Jerusalem, Israel  \n2 Faculty of Medicine, Hebrew University, Jerusalem, Israel  \n3 Unit of Gastroenterology, Lady Davis Carmel Medical Center, Haifa, Israel  \n4 Susanne Levy Gertner Oncogenetics Unit, The Danek Gertner Institute of Human Genetics, Sheba Medical Center, Ramat Gan, Israel  \n5 Gray faculty of Medical and Health Sciences, Tel Aviv University, Tel Aviv, Israel  \n6 Genetics Institute, Soroka Medical Center, Beer-Sheva, Israel  \n7 Faculty of Health Sciences, Ben Gurion University, BeerSheva, Israel  \n8 Recanati Genetics Institute, Rabin Medical Center, Petach Tikva, Israel  \n9 Sharett Institute of Oncology, Hadassah Medical Center, Jerusalem, Israel  \n10 Department of Genetics, Hadassah Medical Center, Jerusalem, Israel  \n11 Davidoff Cancer Center, Rabin Medical Center, Petah Tikva, Israel  \n12 Genetics Institute, Rambam Health Care Campus, Haifa, Israel  \nBackground  \nTelomeres protect chromosomes ends, consist of repetitive nucleotide sequences, and shorten with each cell cycle. Dysfunctional telomeres may lead to inefficient DNA damage repair, genomic instability and tumorigenesis [1] . Telomeric DNA is bound by the shelterin protein complex, which is involved in maintenance of its structure and length regulation [2], and the Protection of Telomeres 1 (POT1) gene encodes one of the shelterin protein subunits [3–5] .  \nPathogenic variants (PVs) in the POT1 gene can cause telomere elongation and are associated with diverse phenotypes; telomere elongation has been associated with POT1 tumor predisposition syndrome (POT1-TP","cbCaic1gIgDwz67s","https://ap.wps.com/l/cbCaic1gIgDwz67s","pdf",952624,"English","# Abstract\n# Background\n## Telomere biology and POT1 function\n## POT1-related tumor predisposition\n# Hereditary breast cancer context\n# Clinical guidelines and surveillance rationale","[{\"question\":\"What is the main goal of this study on POT1 carriers?\",\"answer\":\"To evaluate breast cancer occurrence and characterize genetic, clinical, pathologic, treatment, and outcome features in female heterozygotes with pathogenic POT1 variants.\"},{\"question\":\"Which breast cancer subtypes and biomarkers were observed in the cohort?\",\"answer\":\"Invasive ductal carcinoma was most common; all primary tumors with available data were estrogen receptor positive, one was HER2-enriched, and no triple-negative cancers were observed.\"},{\"question\":\"How did breast cancer outcomes look during follow-up?\",\"answer\":\"After a median follow-up of 110 months, three second breast cancer events occurred and there was no breast-cancer-related mortality reported.\"}]","Breast cancer phenotypes in carriers of pathogenic POT1 variants | PDF",1790110755,15]