Antibody-Drug Conjugates in Breast Cancer: Current Landscape and Future Targets

Authors

  • Jennifer Leigh, MD Department of Medicine, Mount Sinai Hospital, Sinai Health, Toronto, ON, Canada
  • Arif Ali Awan, MD Division of Medical Oncology, Department of Medicine, The Ottawa Hospital, University of Ottawa, Ottawa, ON, Canada Cancer Therapeutics Program, Ottawa Hospital Research Institute, Ottawa, ON, Canada

DOI:

https://doi.org/10.58931/cot.2025.2235

Abstract

Antibody-drug conjugates (ADCs) have transformed therapeutic options for patients with breast cancer, delivering targeted cytotoxic agents with enhanced efficacy, albeit with systemic toxicity. Since the approval of trastuzumab emtansine in 2012, the ADC landscape has rapidly expanded to include agents targeting HER2, TROP-2, and other novel targets. Currently, four ADCs are approved in breast cancer, showing clinical benefit across HER2-positive, HER2-low, hormone receptor (HR)-positive and triple-negative subtypes. Trastuzumab deruxtecan has demonstrated superior outcomes compared to earlier HER2-targeted ADCs and is the preferred treatment in multiple settings. Anti-TROP-2 ADCs, such as sacituzumab govitecan and datopotamab deruxtecan, have provided improvements in progression-free survival in both triple-negative and HR-positive/HER2-negative disease. Ongoing research is exploring additional targets, such as HER3, Nectin-4, B7-H4, and CD166, with several promising candidates showing efficacy in early phase trials. As ADCs move into earlier lines of therapy and combination regimens, understanding optimal sequencing, toxicity management, and cost considerations will be essential. This review summarizes the current ADC landscape in breast cancer and highlights future directions for this rapidly evolving therapeutic class.

Author Biographies

Jennifer Leigh, MD, Department of Medicine, Mount Sinai Hospital, Sinai Health, Toronto, ON, Canada

Dr. Jennifer Leigh received her BSc (Biochemistry) and MSc (Microbiology and Immunology) both from Western University. She completed her residency in internal medicine in 2022, and medical oncology subspeciality training in 2024, both at the University of Ottawa. Currently, she is completing a breast cancer fellowship at the University of Toronto and Mount Sinai Hospital, where she has been awarded a Hold’em for Life Oncology Fellowship to support her research focused on the genitourinary and sexual health impacts of breast cancer treatment.

Arif Ali Awan, MD, Division of Medical Oncology, Department of Medicine, The Ottawa Hospital, University of Ottawa, Ottawa, ON, Canada Cancer Therapeutics Program, Ottawa Hospital Research Institute, Ottawa, ON, Canada

Dr. Arif Ali Awan completed his BSc (Biochemistry) and MDCM in 2013 from McGill University while working on projects in cancer cell signaling and bioinformatics. He completed his residency in internal medicine and medical oncology in 2018 from McGill University. He completed a breast cancer fellowship at the University of Ottawa under the guidance of Drs. Mark Clemons and John Hilton. He’s currently a medical oncologist and an Assistant Professor at the University of Ottawa where he leads the tumor agnostic clinical trials group, breast cancer clinical trials and precision oncology initiatives.

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Published

2025-08-14

How to Cite

Leigh, J., & Ali Awan, A. (2025). Antibody-Drug Conjugates in Breast Cancer: Current Landscape and Future Targets. Canadian Oncology Today, 2(2), 6–19. https://doi.org/10.58931/cot.2025.2235

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Volume 2, Issue 2, Summer 2025

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