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This review summarizes recent liquid-biopsy progress in breast cancer and evaluates key advantages and challenges.",{"@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/current-trends-in-liquid-biopsy-tracking-resistance-in-molecular-breast-cancer-targeted-therapies/371445/",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/current-trends-in-liquid-biopsy-tracking-resistance-in-molecular-breast-cancer-targeted-therapies/371445.png","ImageObject",300,407,{"name":42,"@type":43},"Jacob","Person",{"url":19,"name":45,"@type":46},"DocShare","Organization","application/pdf","2026-10-31","2026-09-23",true,{"@type":52,"interactionType":53,"userInteractionCount":55},"InteractionCounter",{"@type":54},"ViewAction",11,{"@type":57,"mainEntity":58},"FAQPage",[59,65,69],{"name":60,"@type":61,"acceptedAnswer":62},"Why is liquid biopsy considered a better option than needle biopsy for breast cancer monitoring?","Question",{"text":63,"@type":64},"Liquid biopsy is less invasive and does not require organ puncture. It also captures tumor heterogeneity and can reflect molecular changes before metastasis, improving representativeness compared with sampling a single tumor site.","Answer",{"name":66,"@type":61,"acceptedAnswer":67},"How does liquid biopsy help with therapy resistance in molecular breast cancer?",{"text":68,"@type":64},"By measuring circulating components such as ctDNA and detecting relevant biomarkers, it can support earlier identification of patients who may relapse or develop resistance. The review emphasizes the need for timely diagnostic methods linked to resistance mechanisms.",{"name":70,"@type":61,"acceptedAnswer":71},"Which biomarkers and sample types are discussed in the context of liquid biopsy?",{"text":72,"@type":64},"The document highlights nucleic acids/cell-free DNA detection and immunotherapy-related biomarkers, especially PD-L1. It also mentions detection across CTCs, exosomes, plasma, and PBMCs, alongside studies evaluating PD-L1 expression in these sources.","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},371445,1790232026,{"code":4,"msg":82,"data":83},"success",[84,88,92,96,101,106,110,115,120,123,127],{"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":111,"doc_module":4,"doc_module_name":25,"category_name":112,"show_sort_weight":113,"slug":114},8,"Research & Report",30,"research-report",{"id":116,"doc_module":4,"doc_module_name":25,"category_name":117,"show_sort_weight":118,"slug":119},9,"Religion & Spirituality",20,"religion-spirituality",{"id":118,"doc_module":4,"doc_module_name":25,"category_name":121,"show_sort_weight":118,"slug":122},"World Cup","world-cup",{"id":124,"doc_module":4,"doc_module_name":25,"category_name":125,"show_sort_weight":124,"slug":126},10,"Lifestyle","lifestyle",{"id":128,"doc_module":4,"doc_module_name":25,"category_name":129,"show_sort_weight":97,"slug":130},19,"General","general",{"code":4,"msg":82,"data":132},{"doc_id":79,"user_id":133,"nickname":42,"user_avatar":134,"doc_module":4,"category_id":107,"category_name":29,"doc_title":10,"doc_description":12,"doc_content":135,"file_id":136,"file_url":137,"file_type":138,"file_size":139,"view_count":55,"is_deleted":4,"is_public":22,"is_downloadable":22,"audit_status":22,"page_count":140,"language":141,"language_code":8,"site_id":7,"html_lang":8,"table_of_contents":142,"faqs":143,"seo_title":144,"seo_description":12,"update_tm":145,"read_time":146},962084931830,"https://ap-avatar.wpscdn.com/davatar_a8503ba1806abce46bf441b54a3ca4cd","Review  \nCurrent Trends in Liquid Biopsy Tracking Resistance in Molecular Breast Cancer-Targeted Therapies  \nRichard Tancredi 1, Navid Sobhani 2, Martina Catalano 3, Giandomenico Roviello 3, * and Daniele Generali 4  \nAcademic Editor: Yutaka Suzuki  \nReceived: 17 February 2025  \nRevised: 25 March 2025  \nAccepted: 27 March 2025  \nPublished: 9 April 2025  \nCitation: Tancredi, R.; Sobhani, N.; Catalano, M.; Roviello, G.; Generali, D. Current Trends in Liquid Biopsy Tracking Resistance in Molecular Breast Cancer-Targeted Therapies. Genes 2025, 16, 443 . [https://doi.org/10.3390/](https://doi.org/10.3390/)[ ](https://doi.org/10.3390/)genes16040443  \nCopyright: © 2025 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://creativecommons.org/](https://creativecommons.org/)[ ](https://creativecommons.org/)[licenses/by/4.0/](licenses/by/4.0/)) .  \n1 Multidisciplinary Unit of Breast Pathology and Translational Research, Cremona Hospital,  \n26100 Cremona, Italy; [rictanc@hotmail.com](rictanc@hotmail.com)  \n2 Department of Cancer Biology, The University of Texas MD Anderson Cancer Center, Houston, TX 77030, USA; [navid.sobhani@cantab.net](navid.sobhani@cantab.net)  \n3 Department of Health Sciences, Section of Clinical Pharmacology and Oncology, University of Florence, 50139 Florence, Italy; [martina.catalano@unifi.it](martina.catalano@unifi.it)  \n4 Department of Medicine, Surgery and Health Sciences, University of Trieste, 34100 Trieste, Italy;  \ndgenerali@units.it  \n* [Correspondence: giandomenico.roviello@unifi.it](Correspondence: giandomenico.roviello@unifi.it)  \nAbstract: Breast cancer (BC) is the most commonly occurring type of cancer in women, being a major cancer-related cause of mortality worldwide. With the advancement in current therapeutic options, including hormone therapy and targeted therapies, there is a need for more accurate and less invasive options to monitor cancer progression in patients. Liquid biopsy has evolved rapidly, being able to detect small quantities of nucleic acids or cell-free DNA in the blood of BC patients. This method addresses three major issues of needle biopsy: firstly, it is more permissive by being less invasive and does not require needling the organs; secondly, it covers for the heterogeneous nature of the tumor of origin, which could lead to an otherwise inaccurate representation of the cancer-driving mutations; thirdly, it better represents the type of tumor that the primary tumor is going to evolve into before it starts to metastasize. This current review will address the current advancementsin liquid biopsy in the context of BC, highlighting the pros and challenges.  \nKeywords: liquid biopsy; ctDNA; CTC; biomarkers; breast cancer  \n1. Introduction  \nAlmost 12% of the cancers that occur in women worldwide are breast cancer (BC), making it second only to lung cancer in incidence [1] . In 2022, 665,684 women died of BC, which ranks fourth in cancer mortality around the globe [2] . Based on different receptor expressions, BC can be divided into four different subtypes: two luminal subtypes (luminal A and luminal B), the human epidermal growth factor receptor 2 (HER2) subtype, and triplenegative BC (TNBC), which does not express any of these three receptors [3] . Overall, ERpositive and progesterone receptor (PR)-positive breast cancer are called hormone receptorpositive (HR-positive) cancers, which make up 70% of all breast cancer malignancies [3] .  \nBriefly, in hormone receptor-positive (HR+) BC, endocrine therapy (ET) is the base of the first-line therapy. HER2+ patients are treated by adjuvant antibody trastuzumab-based therapy, targeting the HER2 receptor [4] . Antibodies conjugated with chemotherapies targeting HER2+ BC cells have been successfully tested. However, in TNBC where there are no receptors to target, alternative therapies are most needed [","cbCaiuNABYls6tbp","https://ap.wps.com/l/cbCaiuNABYls6tbp","pdf",1053977,14,"English","# Introduction\n## Breast cancer burden and subtypes\n## Therapeutic background and resistance needs\n# Liquid biopsy for monitoring and biomarkers\n## ctDNA and tumor heterogeneity\n## Immunotherapy biomarkers such as PD-L1\n# Resistance mechanisms to breast cancer therapies\n## Drug degradation and receptor changes","[{\"question\":\"Why is liquid biopsy considered a better option than needle biopsy for breast cancer monitoring?\",\"answer\":\"Liquid biopsy is less invasive and does not require organ puncture. It also captures tumor heterogeneity and can reflect molecular changes before metastasis, improving representativeness compared with sampling a single tumor site.\"},{\"question\":\"How does liquid biopsy help with therapy resistance in molecular breast cancer?\",\"answer\":\"By measuring circulating components such as ctDNA and detecting relevant biomarkers, it can support earlier identification of patients who may relapse or develop resistance. The review emphasizes the need for timely diagnostic methods linked to resistance mechanisms.\"},{\"question\":\"Which biomarkers and sample types are discussed in the context of liquid biopsy?\",\"answer\":\"The document highlights nucleic acids/cell-free DNA detection and immunotherapy-related biomarkers, especially PD-L1. It also mentions detection across CTCs, exosomes, plasma, and PBMCs, alongside studies evaluating PD-L1 expression in these sources.\"}]","Current Trends in Liquid Biopsy Tracking Resistance in Molecular Breast Cancer-Targeted Therapies | PDF",1790192093,35]