From Intractable to Treatable: Milestones and Horizons in the Management of HER2+ Breast Cancer

Authors

  • Meredith Li, MD Division of Medical Oncology and Hematology, Princess Margaret Cancer Centre, University Health Network, Toronto, Canada
  • David W. Cescon, MD, PhD, FRCPC Division of Medical Oncology and Hematology, Princess Margaret Cancer Centre, University Health Network, Toronto, Canada

DOI:

https://doi.org/10.58931/cot.2024.1222

Abstract

The human epidermal growth factor receptor 2 (HER2) is a member of the epidermal growth factor receptor (EGFR) family that initiates various signalling pathways that control cell proliferation and tumourigenesis. Historically, approximately 15% of breast cancers have been characterized by overexpression or amplification of HER2, known as “HER2+” breast cancers. This subtype has been associated with an adverse prognosis, along with a high risk of recurrence and worse survival outcomes. However, with the discovery and subsequent development of HER2‑targeted therapies, the clinical course of HER2+ breast cancers has fundamentally changed. Optimizing therapeutic strategies using existing and emerging HER2-targeted therapies to build upon these advances remains a major priority for clinical development and treatment delivery.

In 1998, the American Food and Drug Administration (FDA) and Health Canada approved trastuzumab, the first HER2-targeted therapy. Trastuzumab, a monoclonal antibody that binds to the HER2 receptor, has demonstrated clinical activity and improved outcomes in patients with metastatic HER2+ breast cancer when combined with chemotherapy. Following soon after, the first trial of adjuvant trastuzumab (HERA) demonstrated improvements in outcomes when combined with chemotherapy for early HER2+ breast cancer. More than 25 years after its first approval, trastuzumab retains a central role in the treatment of both early and advanced HER2+ breast cancer and has provided a backbone for both new therapeutic combinations (eg. with small molecule inhibitors of HER2) and new classes of therapeutic agents (antibody drug conjugates [ADC]). These successors of trastuzumab are currently redefining the HER2+ treatment landscape in both advanced and early breast cancer.

Author Biographies

Meredith Li, MD, Division of Medical Oncology and Hematology, Princess Margaret Cancer Centre, University Health Network, Toronto, Canada

Dr. Meredith Li is a breast oncology clinical research fellow at the Princess Margaret Cancer Centre, returning after having left for her medical oncology and internal medicine residency upon graduating from medical school at the University of Toronto. She is actively involved as a sub‑investigator in various clinical trials. Her research interests range from breast cancer evaluation with imaging and ctDNA to therapeutics. She also enjoys teaching and is working towards the Master Teacher certification from the Department of Medicine at University of Toronto. 

David W. Cescon, MD, PhD, FRCPC, Division of Medical Oncology and Hematology, Princess Margaret Cancer Centre, University Health Network, Toronto, Canada

Dr. Cescon is a breast medical oncologist and clinician scientist at the Princess Margaret Cancer Centre. His research program integrates laboratory, translational, and clinical studies, focusing on identifying therapeutic vulnerabilities, mechanisms of drug response and resistance in breast cancer, and the integration of liquid biopsy biomarkers. Dr. Cescon chairs the Canadian Cancer Trials Group IND Committee and co-chairs the NCI NCTN Correlative Sciences Committee. He is actively involved in designing and executing numerous breast cancer clinical trials, spanning from early phase to Phase 3. 

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Published

2024-06-20

How to Cite

Li, M., & Cescon, D. W. (2024). From Intractable to Treatable: Milestones and Horizons in the Management of HER2+ Breast Cancer. Canadian Oncology Today, 1(2), 20–26. https://doi.org/10.58931/cot.2024.1222

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Volume 1, Issue 2, Summer 2024

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Articles

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