[{"data":1,"prerenderedAt":-1},["ShallowReactive",2],{"doc-seo-350026-105":3,"detail-sidebar-cat-0-en-105":79,"doc-detail-350026-en":129},{"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":72,"head_meta":74,"extra_data":76,"updated_unix":78},105,"en","targeting-the-rxr-pathway-for-the-prevention-of-triple-negative-breast-cancer","Targeting the RXR Pathway for the Prevention of Triple-Negative Breast Cancer","","Triple-negative breast cancer (TNBC) remains highly aggressive with limited prognostic improvement, especially for women at high genetic risk. This study evaluates whether nuclear retinoid X receptor (RXR) agonists IRX4204 and 9cUAB30 can prevent ER-negative and TNBC development. Preclinical results show IRX4204 significantly delays mammary tumor formation in multiple ER-negative mouse models with modest toxicities, with complete prevention in some MMTV-ErbB2 mice and substantial tumor-free outcomes in Brca1-deficient mice. Tumor delay associates with reduced Ki-67 and increased cytotoxic T-cell infiltration, supporting further RXR-based prevention trials.",{"@graph":14,"@context":71},[15,34,54],{"@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/targeting-the-rxr-pathway-for-the-prevention-of-triple-negative-breast-cancer/350026/",4,{"url":32,"name":10,"@type":35,"image":36,"author":41,"headline":10,"publisher":44,"fileFormat":47,"inLanguage":8,"description":12,"dateModified":48,"datePublished":48,"encodingFormat":47,"isAccessibleForFree":49,"interactionStatistic":50},"DigitalDocument",{"url":37,"@type":38,"width":39,"height":40},"https://docshare.wps.com/thumbnails/targeting-the-rxr-pathway-for-the-prevention-of-triple-negative-breast-cancer/350026.png","ImageObject",300,407,{"name":42,"@type":43},"\tJames","Person",{"url":19,"name":45,"@type":46},"DocShare","Organization","application/pdf","2026-09-22",true,{"@type":51,"interactionType":52,"userInteractionCount":22},"InteractionCounter",{"@type":53},"ViewAction",{"@type":55,"mainEntity":56},"FAQPage",[57,63,67],{"name":58,"@type":59,"acceptedAnswer":60},"What does the study test regarding TNBC prevention?","Question",{"text":61,"@type":62},"The study tests whether the nuclear RXR agonists IRX4204 and 9cUAB30 can prevent development of ER-negative and triple-negative breast cancers.","Answer",{"name":64,"@type":59,"acceptedAnswer":65},"How did IRX4204 perform in the mouse models?",{"text":66,"@type":62},"IRX4204 significantly delayed mammary tumor formation across three ER-negative mouse models, with modest toxicities; in some MMTV-ErbB2 mice it completely prevented tumors, and 60% of treated Brca1-deficient mice remained tumor-free.",{"name":68,"@type":59,"acceptedAnswer":69},"What biomarker and immune changes were linked to delayed tumors after IRX4204 treatment?",{"text":70,"@type":62},"Delayed tumors showed decreased Ki-67 expression and increased infiltration of cytotoxic T cells, suggesting immune modulation may be important for RXR-based prevention.","https://schema.org",{"og:url":32,"og:type":73,"og:title":10,"og:site_name":45,"og:description":12},"article",{"robots":75,"canonical":32},"index,follow",{"doc_id":77,"site_id":7},350026,1790117434,{"code":4,"msg":80,"data":81},"success",[82,86,90,94,99,104,108,113,118,121,125],{"id":22,"doc_module":4,"doc_module_name":25,"category_name":83,"show_sort_weight":84,"slug":85},"Story & Novel",90,"story-novel",{"id":26,"doc_module":4,"doc_module_name":25,"category_name":87,"show_sort_weight":88,"slug":89},"Literature",80,"literature",{"id":33,"doc_module":4,"doc_module_name":25,"category_name":91,"show_sort_weight":92,"slug":93},"Exam",70,"exam",{"id":95,"doc_module":4,"doc_module_name":25,"category_name":96,"show_sort_weight":97,"slug":98},5,"Comic",60,"comic",{"id":100,"doc_module":4,"doc_module_name":25,"category_name":101,"show_sort_weight":102,"slug":103},6,"Technology",50,"technology",{"id":105,"doc_module":4,"doc_module_name":25,"category_name":29,"show_sort_weight":106,"slug":107},7,40,"healthcare",{"id":109,"doc_module":4,"doc_module_name":25,"category_name":110,"show_sort_weight":111,"slug":112},8,"Research & Report",30,"research-report",{"id":114,"doc_module":4,"doc_module_name":25,"category_name":115,"show_sort_weight":116,"slug":117},9,"Religion & Spirituality",20,"religion-spirituality",{"id":116,"doc_module":4,"doc_module_name":25,"category_name":119,"show_sort_weight":116,"slug":120},"World Cup","world-cup",{"id":122,"doc_module":4,"doc_module_name":25,"category_name":123,"show_sort_weight":122,"slug":124},10,"Lifestyle","lifestyle",{"id":126,"doc_module":4,"doc_module_name":25,"category_name":127,"show_sort_weight":95,"slug":128},19,"General","general",{"code":4,"msg":80,"data":130},{"doc_id":77,"user_id":131,"nickname":42,"user_avatar":132,"doc_module":4,"category_id":105,"category_name":29,"doc_title":10,"doc_description":12,"doc_content":133,"file_id":134,"file_url":135,"file_type":136,"file_size":137,"view_count":22,"is_deleted":4,"is_public":22,"is_downloadable":22,"audit_status":22,"page_count":109,"language":138,"language_code":8,"site_id":7,"html_lang":8,"table_of_contents":139,"faqs":140,"seo_title":141,"seo_description":12,"update_tm":142,"read_time":116},2336474466412,"https://ap-avatar.wpscdn.com/davatar_155a257f0dc6eb9ab79c44ca47cae57d","Targeting the RXR Pathway for the Prevention of Triple-Negative Breast Cancer  \nCassandra L. Moyer1, Jamal L. Hill1, Darian Coleman1, Amanda Lanier1, Yanxia Ma1, Xiaoqian Liu2, Jitesh Kawedia2, Alejandro Contreras3, Vidyasagar Vuligonda4,  \nMichelle I. Savage1, Martin E. Sanders4, Altaf Mohammed5, Shizuko Sei5, Powel H. Brown1, and Abhijit Mazumdar1  \n|  |  |  | A |  | B | S |  | T | R |  | A |  | C | T |  |  |  |  |  |  |  |  |  |  |  |  |  |  |  |  |  |  |  |  |  |  |  |  |  |  |  |  |  |  |  |  |  |  |  |  |  |  |  |  |  |  |  |  |  |  |  |  |  |  |  |  |  |  |  |  |  |  |  |  |  |  |  |  |  |  |  |  |  |  |  |  |  |  |  |  |  |  |  |  |  |  |  |  |  |  |\n| --- | --- | --- | --- | --- | --- | --- | --- | --- | --- | --- | --- | --- | --- | --- | --- | --- | --- | --- | --- | --- | --- | --- | --- | --- | --- | --- | --- | --- | --- | --- | --- | --- | --- | --- | --- | --- | --- | --- | --- | --- | --- | --- | --- | --- | --- | --- | --- | --- | --- | --- | --- | --- | --- | --- | --- | --- | --- | --- | --- | --- | --- | --- | --- | --- | --- | --- | --- | --- | --- | --- | --- | --- | --- | --- | --- | --- | --- | --- | --- | --- | --- | --- | --- | --- | --- | --- | --- | --- | --- | --- | --- | --- | --- | --- | --- | --- | --- | --- | --- | --- |\n| 􀀶 |  | Prophylactic treatment with selective estrogen receptor (ER) modulators and aromatase inhibitors targeting the nuclear ER can prevent the formation of ER-positive tumorsin women at high risk of breast cancer but does not prevent ER-negative and triple-negative subtypes. In this study, we tested whether nuclear retinoid X receptor (RXR) agonists, IRX4204 and 9cUAB30, which have been evaluated in clinical trials, could prevent the development of ER-negative and triple-negative breast cancers. Our study demonstrates that IRX4204 significantly delays the formation of mammary tumors in three ER-negative mouse models: MMTV-ErbB2, C3(1)/SV40-TAg, and Brca1-deficient with modest toxicities. In some of the MMTV-ErbB2 mice, IRX4204 completely prevented mammary tumor formation, and 60% of the IRX4204-treated Brca1-deficient mice remained tumor-free when all vehicle-treated mice had formed tumors. |  |  |  |  |  |  |  |  |  |  |  |  |  |  |  |  |  |  |  |  |  |  |  |  |  |  |  |  |  |  |  |  |  |  |  |  |  |  |  |  |  |  |  |  |  |  |  |  |  | 9cUAB30 treatment also delays tumor formation in Brca1-deficient mice, albeit to a lesser extent. Biomarker analysis revealed that delayed tumors arising after IRX4204 treatment had decreased Ki-67 expression and increased infiltration of cytotoxic T cells. Our preclinical study data support the further evaluation of use of RXR agonists for the prevention of triplenegative breast cancer.\u003Cbr>Prevention Relevance: Treatment with the RXR agonist IRX4204 significantly delays tumor formation and increases CD8-positive T-cell infiltration in ER-negative murine breast cancer models. This suggests that immune modulation may be critical for rexinoid-based prevention of ER-negative mammary tumors and supports their use in future breast cancer prevention trials for high-risk individuals.\u003Cbr>See related Spotlight, p. 133 |  |  |  |  |  |  |  |  |  |  |  |  |  |  |  |  |  |  |  |  |  |  |  |  |  |  |  |  |  |  |  |  |  |  |  |  |  |  |  |  |  |  |  |  |  |  |  |  |\n\nIntroduction  \nDespite the advancements in breast cancer treatment, breast cancer incidence is on the rise (1) . Women of African descent, women with a strong family history of cancer, and women born with a deleterious variant in risk genes, such as BRCA1 or BRCA2, have an even greater chance of developing breast cancer in their lifetime (2) . It is also known that familial breast cancer associated with BRCA1 mutations is more likely to be triple-negative breast cancer (TNBC; ref. 3) .  \n1Department of Clinical Cancer Prevention, The University of Texas MD Anderson Cancer Center, Houston, Texas. 2Department of Pharmacy Pharmacology Research, The University of Texas MD Anderson Cancer Center,","cbCaignlVNwN80Zl","https://ap.wps.com/l/cbCaignlVNwN80Zl","pdf",20244027,"English","# Introduction\n## Background on breast cancer risk and TNBC\n## Limitations of current prevention strategies\n## Rationale for RXR agonist evaluation","[{\"question\":\"What does the study test regarding TNBC prevention?\",\"answer\":\"The study tests whether the nuclear RXR agonists IRX4204 and 9cUAB30 can prevent development of ER-negative and triple-negative breast cancers.\"},{\"question\":\"How did IRX4204 perform in the mouse models?\",\"answer\":\"IRX4204 significantly delayed mammary tumor formation across three ER-negative mouse models, with modest toxicities; in some MMTV-ErbB2 mice it completely prevented tumors, and 60% of treated Brca1-deficient mice remained tumor-free.\"},{\"question\":\"What biomarker and immune changes were linked to delayed tumors after IRX4204 treatment?\",\"answer\":\"Delayed tumors showed decreased Ki-67 expression and increased infiltration of cytotoxic T cells, suggesting immune modulation may be important for RXR-based prevention.\"}]","Targeting the RXR Pathway for the Prevention of Triple-Negative Breast Cancer | PDF",1790086810]