Review ArticlesAntibody-Drug Conjugates in Breast Cancer: What Is Beyond HER2?Nicolò, Eleonora MD∗,†; Repetto, Matteo MD∗,†; Boscolo Bielo, Luca MD∗,†; Tarantino, Paolo MD∗,†,‡; Curigliano, Giuseppe MD, PhD∗,† Author Information From the ∗Division of New Drugs and Early Drug Development, European Institute of Oncology IRCCS †Department of Oncology and Hemato-Oncology, University of Milan, Milan, Italy ‡Dana Farber Cancer Institute, Harvard Medical School, Boston, MA. Conflicts of Interest and Source of Funding: G.C. reports personal fees for consulting, advisory role, and speakers' bureau from Roche/Genentech, Novartis, Pfizer, Lilly, Foundation Medicine, Samsung, and Daiichi Sankyo; honoraria from Ellipses Pharma; and fees for travel and accommodations from Roche/Genentech and Pfizer. M.R. reports fees for travel and accommodation from Sanofi. All the competing interests were outside the submitted work. For the remaining authors, none were declared. Reprints: Giuseppe Curigliano, MD, PhD, Division of New Drugs and Early Drug Development for Innovative Therapies, European Institute of Oncology, IRCCS, Via Ripamonti 435, 20141 Milan, Italy. E-mail: [email protected]. The Cancer Journal: 11/12 2022 - Volume 28 - Issue 6 - p 436-445 doi: 10.1097/PPO.0000000000000629 Buy Metrics Abstract The therapeutic landscape of patients with breast cancer has changed significantly with the introduction of antibody-drug conjugates (ADCs). Although human epidermal growth factor receptor 2 (HER2) has been the centerpiece of ADC development, potentially any surface antigen with differential expression between tumor and normal cells may be suitable for targeting with ADCs. Exploration of new targets is critical to expand the fraction of patients who can benefit from ADCs. Sacituzumab govitecan, an anti–trophoblast cell surface antigen 2 ADC, is the only non–anti-HER2 ADC approved for breast cancer to date, with several novel ADCs directed against novel targets (e.g., HER3, LIV-1) at various stages of preclinical and clinical development. The aim of this review is to provide an overview of clinical trials investigating ADCs targeting novel antigens. We discuss the optimal characteristics of the target to be exploited in ADCs' design and potential future challenges in the evolving field of ADCs such as biomarker assessment, patient selection, and sequencing of ADCs. Copyright © 2022 Wolters Kluwer Health, Inc. All rights reserved.