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The article reviews molecular mechanisms driving endocrine resistance, including estrogen receptor gene mutations, signaling pathway reactivation, epigenetic alterations, and cell-cycle changes. It further details how tumor microenvironment (TME) components—both cellular (cancer-associated fibroblasts, immune cells, cancer stem cells) and acellular (collagen, fibronectin, laminin)—support resistance development through bidirectional tumor-TME interactions, summarizing the relationship to inform newer therapeutic approaches.",{"@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/the-role-of-the-tumor-microenvironment-in-endocrine-therapy-resistance-in-hormone-receptor-positive-breast-cancer/378375/",{"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/the-role-of-the-tumor-microenvironment-in-endocrine-therapy-resistance-in-hormone-receptor-positive-breast-cancer/378375.png","ImageObject",300,407,{"name":92,"@type":93},"Mimi","Person",{"url":74,"name":95,"@type":96},"DocShare","Organization","application/pdf","2026-09-26","2026-09-24",true,{"@type":102,"interactionType":103,"userInteractionCount":81},"InteractionCounter",{"@type":104},"ViewAction",{"@type":106,"mainEntity":107},"FAQPage",[108,114,118],{"name":109,"@type":110,"acceptedAnswer":111},"Why is endocrine therapy resistance a major concern in hormone receptor-positive breast cancer?","Question",{"text":112,"@type":113},"Endocrine therapy can significantly improve prognosis, but resistance emerges and undermines treatment effectiveness, becoming a major health concern for patients.","Answer",{"name":115,"@type":110,"acceptedAnswer":116},"What mechanisms contribute to endocrine therapy resistance?",{"text":117,"@type":113},"Resistance involves multiple interacting factors, including estrogen receptor gene abnormalities, deregulated signaling pathway activation, epigenetic regulation, altered cell-cycle control, and tumor stem cell-like cells.",{"name":119,"@type":110,"acceptedAnswer":120},"How does the tumor microenvironment influence endocrine therapy resistance?",{"text":121,"@type":113},"The tumor microenvironment (TME) provides local cellular and non-cellular conditions that create bidirectional signaling with tumor cells, affecting survival, metastasis, and drug resistance.","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},378375,1790302038,{"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":81,"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},2336477974920,"https://ap-avatar.wpscdn.com/davatar_155a257f0dc6eb9ab79c44ca47cae57d","TYPE Review  \nPUBLISHED 13 October 2023  \nDOI 10.3389/fendo.2023.1261283  \nOPEN ACCESS  \nEDITED BY  \nEva Surmacz,  \nAllysta Pharmaceuticals, Inc., United States  \nREVIEWED BY  \nPrathibha Ranganathan,  \nCentre for Human Genetics (CHG), India Rosa Sirianni,  \nUniversity of Calabria, Italy  \n*CORRESPONDENCE Gautam Sethi  \n [phcgs@nus.edu.sg](phcgs@nus.edu.sg)[ ](phcgs@nus.edu.sg)Geng Wang  \n [ztwg0120@163.com](ztwg0120@163.com)  \nRECEIVED 19 July 2023  \nACCEPTED 29 September 2023  \nPUBLISHED 13 October 2023  \nCITATION  \nYuan J, Yang L, Li Z, Zhang H, Wang Q, Huang J, Wang B, Mohan CD, Sethi G and Wang G (2023) The role of the tumor microenvironment in endocrine therapy resistance in hormone receptor-positive breast cancer.  \nFront. Endocrinol. 14:1261283 .  \ndoi: 10.3389/fendo.2023.1261283  \nCOPYRIGHT  \n© 2023 Yuan, Yang, Li, Zhang, Wang, Huang, Wang, Mohan, Sethi and Wang. This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY) . The use, distribution or reproduction in other forums is permitted, provided the original author(s) and the copyright owner(s) are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.  \nThe role of the tumor microenvironment in endocrine therapy resistance in hormone receptor-positive breast cancer  \nJie Yuan1,2, Li Yang3, Zhi Li 1, Hua Zhang 1, Qun Wang 1, Jun Huang 1, Bei Wang 1, Chakrabhavi Dhananjaya Mohan 4,5, Gautam Sethi 2* and Geng Wang 1*  \n1 Department of Endocrine and Vascular Surgery, Taihe Hospital, Hubei University of Medicine, Hubei, China, 2 Department of Pharmacology, Yong Loo Lin School of Medicine, National University of Singapore, Singapore, Singapore, 3 Department of Clinical Laboratory Medicine, Taihe Hospital, Hubei University of Medicine, Hubei, China, 4 Department of Studies in Molecular Biology, University of Mysore, Manasagangotri, Mysore Karnataka, India, 5 FEST Division, CSIR-Indian Institute of Toxicology Research, Lucknow, Uttar Pradesh, India  \nEndocrine therapy is the prominent strategy for the treatment of hormonepositive breast cancers. The emergence of resistance to endocrine therapy is a major health concern among hormone-positive breast cancer patients. Resistance to endocrine therapy demands the design of newer therapeutic strategies. The understanding of underlying molecular mechanisms of endocrine resistance, components of the tumor microenvironment (TME), and interaction of resistant breast cancer cells with the cellular/acellular components of the intratumoral environment are essential to formulate new therapeutic strategies for the treatment of endocrine therapy-resistant breast cancers. In the first half of the article, we have discussed the general mechanisms (including mutations in estrogen receptor gene, reregulated activation of signaling pathways, epigenetic changes, and cell cycle alteration) responsible for endocrine therapy resistance in hormone-positive breast cancers. In the latter half, we have emphasized the precise role of cellular (cancer-associated fibroblasts, immune cells, and cancer stem cells) and acellular components (collagen, fibronectin, and laminin) of TME in the development of endocrine resistance in hormone-positive breast cancers. In sum, the article provides an overview of the relationship between endocrine resistance and TME in hormone-positive breast cancers.  \nKEYWORDS  \nbreast cancer, endocrine therapy resistance, estrogen, tumor microenvironment, drug resisitance  \nFrontiers in Endocrinology 01 [frontiersin.org](frontiersin.org)  \n1 Introduction  \nBreast cancer is the most common malignant tumor in women, which seriously endangers women’s health. Hormone receptorpositive breast cancer accounts for approximately 60-75%, and endocrine therapy can significantly improve the prognosis of hormone receptor-positive breast cancer pati","cbCaimWpCXPAuLWn","https://ap.wps.com/l/cbCaimWpCXPAuLWn","pdf",2117568,11,"English","# Introduction\n## Endocrine therapy and drug resistance in hormone receptor-positive breast cancer\n## Mechanisms of endocrine therapy resistance\n## Role of the tumor microenvironment (TME)\n## Cellular and acellular components of TME","[{\"question\":\"Why is endocrine therapy resistance a major concern in hormone receptor-positive breast cancer?\",\"answer\":\"Endocrine therapy can significantly improve prognosis, but resistance emerges and undermines treatment effectiveness, becoming a major health concern for patients.\"},{\"question\":\"What mechanisms contribute to endocrine therapy resistance?\",\"answer\":\"Resistance involves multiple interacting factors, including estrogen receptor gene abnormalities, deregulated signaling pathway activation, epigenetic regulation, altered cell-cycle control, and tumor stem cell-like cells.\"},{\"question\":\"How does the tumor microenvironment influence endocrine therapy resistance?\",\"answer\":\"The tumor microenvironment (TME) provides local cellular and non-cellular conditions that create bidirectional signaling with tumor cells, affecting survival, metastasis, and drug resistance.\"}]","The role of the tumor microenvironment in endocrine therapy resistance in hormone receptor-positive breast cancer | PDF",1790229671,28]