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This review surveys major TME components and explains how they function as prognostic and predictive biomarkers. It evaluates methods for TME assessment, including immunohistochemistry and gene-expression profiling, and discusses clinical use in therapeutic decision-making. Finally, it reviews TME-targeted therapeutic strategies and their potential to improve patient stratification and support personalized therapies.",{"@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/targeting-the-tumor-microenvironment-in-breast-cancer-prognostic-and-predictive-significance-and-therapeutic-opportunities/384298/",{"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/targeting-the-tumor-microenvironment-in-breast-cancer-prognostic-and-predictive-significance-and-therapeutic-opportunities/384298.png","ImageObject",300,407,{"name":92,"@type":93},"Well Done","Person",{"url":74,"name":95,"@type":96},"DocShare","Organization","application/pdf","2026-11-01","2026-09-24",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},"Why is the tumor microenvironment (TME) important in breast cancer?","Question",{"text":112,"@type":113},"The TME influences breast cancer development, progression, and treatment response through interactions among tumor cells and diverse supporting cell populations and stromal components.","Answer",{"name":115,"@type":110,"acceptedAnswer":116},"Which biomarker and assessment approaches are discussed for the TME?",{"text":117,"@type":113},"The review examines TME components as prognostic and predictive biomarkers and discusses assessment techniques such as immunohistochemistry and gene-expression profiling.",{"name":119,"@type":110,"acceptedAnswer":120},"What therapeutic opportunities arise from targeting the TME?",{"text":121,"@type":113},"Therapeutic strategies aimed at the TME are reviewed, with emphasis on how they may improve clinical outcomes by modulating tumor–TME communication.","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},384298,1790923702,{"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},5909892210082,"https://ap-avatar.wpscdn.com/avatar/56001069da27c9f41e8?x-image-process=image/resize,m_fixed,w_180,h_180&k=1789614185077863061","Review  \nTargeting the Tumor Microenvironment in Breast Cancer: Prognostic and Predictive Significance and  \nTherapeutic Opportunities  \nMar½a A. Dom½nguez-Cejudo 1,2, *,†, Ana Gil-Torralvo 1,2,3,†, Mânica Cejuela 3, Sonia Molina-Pinelo 1,2 and Javier Salvador Bofill 1,2,3, *  \nCitation: Domínguez-Cejudo, M.A.; Gil-Torralvo, A.; Cejuela, M.;  \nMolina-Pinelo, S.; Salvador Bofill, J. Targeting the Tumor Microenvironment in Breast Cancer: Prognostic and Predictive Significance and Therapeutic Opportunities. Int. J. Mol. Sci. 2023, 24, 16771. [https://doi.org/](https://doi.org/)[ ](https://doi.org/)[10.3390/ijms242316771](10.3390/ijms242316771)  \nAcademic Editor: Cristina Belgiovine  \nReceived: 25 October 2023  \nRevised: 23 November 2023  \nAccepted: 24 November 2023  \nPublished: 26 November 2023  \nCopyright: © 2023 by the authors. Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license ([https://](https://)[ ](https://)[creativecommons.org/licenses/by/](creativecommons.org/licenses/by/)[ ](creativecommons.org/licenses/by/)[4.0/](4.0/)) .  \n1 Institute of Biomedicine of Seville (IBiS), HUVR, CSIC, Universidad de Sevilla, 41013 Seville, Spain; [smolina-ibis@us.es](smolina-ibis@us.es) (S.M.-P.)  \n2 Andalusian—Roche Network Mixed Alliance in Precision Medical Oncology, 41092 Sevilla, Spain  \n3 Medical Oncology Department, Virgen del Rocio Hospital, 41013 Seville, Spain  \n* Correspondence: mdcejudo-ibis@us.es (M.A.D.-C.); [franciscoj.salvador.sspa@juntadeandalucia.es](franciscoj.salvador.sspa@juntadeandalucia.es) (J.S.B.)† These authors contributed equally to this work.  \nAbstract: Breast cancer is one of the most prevalent tumors among women. Its prognosis and treatment outcomes depend on factors related to tumor cell biology. However, recent studies have revealed the critical role of the tumor microenvironment (TME) in the development, progression, and treatment response of breast cancer. In this review, we explore the different components of the TME and their relevance as prognostic and predictive biomarkers in breast cancer. In addition, techniques for assessing the tumor microenvironment, such as immunohistochemistry or gene expression profiling, and their clinical utility in therapeutic decision-making are examined. Finally, therapeutic strategies targeting the TME are reviewed, highlighting their potential clinical benefits. Overall, this review emphasizes the importance of the TME in breast cancer and its potential as a clinical tool for better patient stratification and the design of personalized therapies.  \nKeywords: breast cancer; tumor microenvironment; biomarkers; targeted therapy  \n1. Introduction  \nBreast cancer (BC) is a prevalent and lethal disease, affecting more women than men and exhibiting geographical disparities [1] . It is considered a heterogeneous disease, and its classic prognostic assessment has relied on clinical and histopathological criteria, including lymph node involvement, tumor size, and tumor cell differentiation [2] .  \nImmunohistochemical (IHC) markers such as estrogen receptor (ER), progesterone receptor (PR), and human epidermal growth factor receptor 2 (HER2) have refined subtype differentiation and influenced treatment decisions. Proliferation markers like Ki67 also offer prognostic value [3–5] . Advances in molecular biology have allowed platforms like Oncotype to provide prognostic and predictive information for the selection of patients who should undergo adjuvant chemotherapy [6] . Furthermore, in recent years, the targeted sequencing of specific genes, such as phosphatidylinositol-4,5-bisphosphate 3-kinase catalytic subunit alpha (PIK3CA) or estrogen receptor alpha 1 (ESR1), has been introduced in clinical decision-making as their mutational profiles provide predictive information regarding the response to certain treatments.  \nWhile genetic and epigenetic factors significantly contribute","cbCaihyBBvUVd5Xa","https://ap.wps.com/l/cbCaihyBBvUVd5Xa","pdf",744667,14,"English","# Introduction\n# Components of the Breast Cancer Microenvironment and Their Value as Prognostic and Predictive Factors","[{\"question\":\"Why is the tumor microenvironment (TME) important in breast cancer?\",\"answer\":\"The TME influences breast cancer development, progression, and treatment response through interactions among tumor cells and diverse supporting cell populations and stromal components.\"},{\"question\":\"Which biomarker and assessment approaches are discussed for the TME?\",\"answer\":\"The review examines TME components as prognostic and predictive biomarkers and discusses assessment techniques such as immunohistochemistry and gene-expression profiling.\"},{\"question\":\"What therapeutic opportunities arise from targeting the TME?\",\"answer\":\"Therapeutic strategies aimed at the TME are reviewed, with emphasis on how they may improve clinical outcomes by modulating tumor–TME communication.\"}]","Targeting the Tumor Microenvironment in Breast Cancer: Prognostic and Predictive Significance and Therapeutic Opportunities | PDF",1790262092,35]