Evolving concepts in HER2-low breast cancer: Genomic insights, definitions, and treatment paradigms

Whitney L. Hensing; Emily L. Podany; James J. Sears; Shaili Tapiavala; Andrew A. Davis

doi:10.18632/oncotarget.28680

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Evolving concepts in HER2-low breast cancer: Genomic insights, definitions, and treatment paradigms

Whitney L. Hensing, Emily L. Podany, James J. Sears, Shaili Tapiavala and Andrew A. Davis _

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Oncotarget. 2025; 16:11-27. https://doi.org/10.18632/oncotarget.28680

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Abstract

Whitney L. Hensing1, Emily L. Podany2, James J. Sears2, Shaili Tapiavala2 and Andrew A. Davis2

1 Saint Luke’s Cancer Institute, University of Missouri-KC School of Medicine, Kansas City, MO 64111, USA

2 Department of Medicine, Division of Oncology, Washington University in St. Louis School of Medicine, St. Louis, MO 63110, USA

Correspondence to:

Andrew A. Davis,

email:

[email protected]

Keywords: breast cancer; HER2-low; genomics

Received: July 17, 2024 Accepted: December 20, 2024 Published: January 20, 2025

Copyright: © 2025 Hensing et al. This is an open access article distributed under the terms of the Creative Commons Attribution License (CC BY 4.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.

ABSTRACT

Human epidermal growth factor receptor 2 (HER2)-low breast cancer has recently emerged as a new clinical subtype of breast cancer, benefiting from treatment with novel anti-HER2 antibody-drug conjugates. Emergence of HER2-low as a clinical subtype has raised several important questions related to the (i) biology and prognostic significance of HER2-low breast cancer, (ii) definition of HER2-low breast cancer, and (iii) clinical management of HER2-low breast cancer within existing treatment paradigms. Previously, our group evaluated the genomic landscape and prognostic significance of HER2-low using circulating tumor DNA in patients with metastatic breast cancer, determining that HER2-low did not represent a unique biologic subtype. In this review, we discuss our findings in the context of existing literature on HER2-low breast cancer and propose how best to translate current evidence into clinical management of HER2-low breast cancer.

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Evolving concepts in HER2-low breast cancer: Genomic insights, definitions, and treatment paradigms

Abstract