Review ArticlesAntibody-Drug Conjugates in Breast Cancer: Spotlight on HER2Abelman, Rachel Occhiogrosso MD; Medford, Arielle MD; Spring, Laura MD; Bardia, Aditya MD, MPH, FASCO Author Information From the Massachusetts General Hospital, Harvard Medical School, Boston, MA. Conflicts of Interest and Source of Funding: L.S. is consultant to Novartis, PUMA, G1 therapeutics, and Daiichi Pharma and has contracted research/grant (to institution) from Phillips, Merck, Genentech, GSK, Gilead, and Eli Lilly. A.B. is consultant or is on advisory board of Pfizer, Novartis, Genentech, Merck, Radius Health, Immunomedics/Gilead, Sanofi, Daiichi Pharma/AstraZeneca, Phillips, Eli Lilly, and Foundation Medicine and has contracted research/grant (to institution) from Genentech, Novartis, Pfizer, Merck, Sanofi, Radius Health, Immunomedics/Gilead, Daiichi Pharma/AstraZeneca, and Eli Lilly. For the remaining authors, none were declared. This study involves a review of the literature and did not involve any studies with human or animal subjects performed by any of the authors. Data sharing is not applicable to this article as no data sets were generated or analyzed during the writing of this article. The named authors meet the International Committee of Medical Journal Editors criteria for authorship of this manuscript, take responsibility for the integrity of the work as a whole, and have given final approval for the version to be published. Reprints: Aditya Bardia, MD, MPH, FASCO, Massachusetts General Hospital, 55 Fruit St, Boston, MA 02114. E-mail: [email protected]. The Cancer Journal: 11/12 2022 - Volume 28 - Issue 6 - p 423-428 doi: 10.1097/PPO.0000000000000634 Buy Metrics Abstract Antibody-drug conjugates (ADCs) are composed of monoclonal antibodies linked to a cytotoxic payload, enabling targeted delivery of more potent chemotherapy. In the past decade, there has been rapid development of ADCs aimed at different types of breast cancer. The success of the monoclonal antibody trastuzumab has led to the evolution of several ADCs targeting HER2-positive breast cancer. Trastuzumab-emtansine, the first approved ADC targeting HER2-positive breast cancer, has become standard of care for patients with high-risk early-stage HER2-positive breast cancer who have residual disease after neoadjuvant chemotherapy. More recently, the observation of the bystander effect, in which ADCs target both antigen-positive cells and adjacent antigen-negative cells, has led to the reclassification of “HER2-low” breast cancer and the development of trastuzumab-deruxtecan to target this population. This article reviews the history of HER2-directed ADCs in breast cancer as well as ongoing ADCs in development. Copyright © 2022 Wolters Kluwer Health, Inc. All rights reserved.