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Over the last two decades, advances in ADC design and research—especially in breast cancer—have reshaped treatment paradigms and support emerging classifications such as “HER2-low”. This review surveys key ADCs including T-DM1, T-DXd, sacituzumab govitecan, and other emerging agents, highlighting benefits, opportunities, challenges, and future research directions to improve target selection, combination strategies, and drug safety.",{"@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/antibodydrug-conjugates-in-breast-cancer-ascent-to-destiny-and-beyond-a-2023-review/382636/",{"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/antibodydrug-conjugates-in-breast-cancer-ascent-to-destiny-and-beyond-a-2023-review/382636.png","ImageObject",300,407,{"name":92,"@type":93},"Riley West","Person",{"url":74,"name":95,"@type":96},"DocShare","Organization","application/pdf","2026-11-03","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},"What are antibody–drug conjugates (ADCs) and how do they work in breast cancer treatment?","Question",{"text":112,"@type":113},"ADCs are designed therapeutics that target cells expressing specific cancer antigens using directed antibody–drug delivery. After binding, the system releases a cytotoxic chemotherapeutic payload to kill cancer cells, including through direct cytotoxicity, antibody-mediated effects, and the bystander effect.","Answer",{"name":115,"@type":110,"acceptedAnswer":116},"Why is “HER2-low” considered an important emerging subtype in breast cancer ADC therapy?",{"text":117,"@type":113},"Recent landmark publications have changed breast cancer treatment paradigms and introduced a potential new subtype, “HER2-low”. 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M. Mata 2, Ana Elisa Lohmann 2 and Phillip S. Blanchette 2, *  \nCitation: Xiao, T.; Ali, S.; Mata,  \nD.G.M.M.; Lohmann, A.E.; Blanchette, P.S. Antibody–Drug Conjugates in Breast Cancer: Ascent to Destiny and Beyond—A 2023 Review. Curr. Oncol. 2023, 30, 6447–6461. [https://doi.org/](https://doi.org/)[ ](https://doi.org/)[10.3390/curroncol30070474](10.3390/curroncol30070474)  \nReceived: 29 May 2023  \nRevised: 23 June 2023  \nAccepted: 27 June 2023  \nPublished: 6 July 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 Schulich School of Medicine, Western University, London, ON N6A 5C1, Canada  \n2 Division of Medical Oncology, Department of Oncology, London Health Sciences Centre, Western University, London, ON N6A 5W9, Canada  \n* [Correspondence: phillip.blanchette@lhsc.on.ca](Correspondence: phillip.blanchette@lhsc.on.ca); Tel.: +1-519-695-8640; Fax: +1-519-685-8624  \nAbstract: Antibody–drug conjugates (ADCs) are revolutionizing cancer treatment, adding another important new class of systemic therapy. ADCs are a specially designed class of therapeutics that target cells expressing specific cancer antigens using directed antibody–drug delivery and release a cytotoxic chemotherapeutic payload. Over the past two decades, improvements in ADC design, development, and research, particularly in breast cancer, have led to several recent landmark publications. These advances have significantly changed various treatment paradigms and revamped traditional classifications of breast cancer with the introduction of a potential new subtype: “HER2-low”. This review will focus on several ADCs developed for breast cancer treatment, including trastuzumab emtansine (T-DM1), trastuzumab deruxtecan (T-DXd), sacituzumab govitecan (SG) and other newer emerging agents. It will provide an overview of the role of ADCs in breast cancer and discuss the opportunities and challenges they present. Additionally, our review will discuss future research directions to improve the selection of targets, combination therapies, and aim to improve drug safety. Important first-line metastatic and adjuvant clinical trials are underway, which may expand the role of ADC therapy in breast cancer. We foresee ADCs driving a new era of breast cancer treatment, adding to the steady incremental survival advantage observed in recent years.  \nKeywords: antibody–drug conjugate (ADCs); breast cancer; HER2-low  \n1. Introduction: Development and History of ADCs in Breast Cancer  \nTargeted drug delivery was originally described by Dr. Paul Ehrlich, known as the `magic bullet concept', whereby therapeutic agents could be directed precisely against microbes or cancerous cells nearly 100 years ago [1] . Nonetheless, for much of the 20th century, targeted cancer therapy was not feasible and cytotoxic chemotherapy remained the mainstay of treatment. The first breakthrough in the development of ADCs was monoclonal antibody therapy directed against cancer cells. Antibodies, also known as immunoglobulins, are proteins of the humoral immune system produced in response to a foreign antigen. In the context of therapeutic use against a specific cancer antigen, scientists can create a specific antibody clone called a monoclonal antibody. Through selective interaction with cancer cell antigens, monoclonal antibodies can directly target cancer cells with minimal interference with normal tissue function. The concept of monoclonal antibody-directed cancer therapy is exemplified by trastuzumab, a monoclonal antibody targeted against the human epidermal growt","cbCaipNhjYJWP9fX","https://ap.wps.com/l/cbCaipNhjYJWP9fX","pdf",497455,15,"English","# Abstract\n# Introduction: Development and History of ADCs in Breast Cancer\n## Magic bullet concept and early targeted therapy\n## Monoclonal antibodies and trastuzumab\n## Regulatory milestone: first ADC approval and withdrawal\n## ADC structure and mechanisms of cytotoxicity\n## Determinants of ADC efficacy (target affinity, linker release, stability, payload potency)","[{\"question\":\"What are antibody–drug conjugates (ADCs) and how do they work in breast cancer treatment?\",\"answer\":\"ADCs are designed therapeutics that target cells expressing specific cancer antigens using directed antibody–drug delivery. After binding, the system releases a cytotoxic chemotherapeutic payload to kill cancer cells, including through direct cytotoxicity, antibody-mediated effects, and the bystander effect.\"},{\"question\":\"Why is “HER2-low” considered an important emerging subtype in breast cancer ADC therapy?\",\"answer\":\"Recent landmark publications have changed breast cancer treatment paradigms and introduced a potential new subtype, “HER2-low”. This reflects how ADC target biology and classification can influence therapeutic decisions.\"},{\"question\":\"Which ADCs are highlighted for breast cancer in this 2023 review?\",\"answer\":\"The review focuses on ADCs developed for breast cancer treatment, including trastuzumab emtansine (T-DM1), trastuzumab deruxtecan (T-DXd), sacituzumab govitecan (SG), and other newer emerging agents.\"}]","Antibody–Drug Conjugates in Breast Cancer: Ascent to Destiny and Beyond - A 2023 Review | PDF",1790251446,38]