Navigating the HER2-Low Paradigm in Breast Oncology: New Standards, Future Horizons

Author:

Tarantino Paolo1234ORCID,Curigliano Giuseppe34ORCID,Tolaney Sara M.12ORCID

Affiliation:

1. 1Dana-Farber Cancer Institute, Boston, Massachusetts.

2. 2Harvard Medical School, Boston, Massachusetts.

3. 3Division of New Drugs and Early Drug Development, European Institute of Oncology, IRCCS, Milan, Italy.

4. 4Department of Oncology and Hemato-Oncology, University of Milan, Milan, Italy.

Abstract

Summary: The confirmation of the HER2-low paradigm is expected to have a major impact in breast oncology. About half of all breast cancers harbor HER2-low expression, which can be targeted with the anti-HER2 antibody–drug conjugate trastuzumab deruxtecan (T-DXd), leading to a relevant survival benefit in the metastatic setting. Given this observation, treatment algorithms for both hormone receptor–positive and triple-negative breast cancer are expected to significantly evolve in the next future. Several challenges, however, remain in the interpretation of HER2-low expression related to its biological role, its pathologic diagnosis, and the definition itself of HER2-low. In this article, we recapitulate the current knowledge on HER2-low breast cancer, discussing whether it should be considered a distinct subtype, how it should be implemented in the clinic, and how its definition may evolve in the coming years with the evolution of our clinical and translational knowledge.

Publisher

American Association for Cancer Research (AACR)

Subject

Oncology

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