ARTICLE
Volume 10,Issue 4
14 April 2026
HER2-Low Breast Cancer: Clinicopathologic Landscape, Prognostic Controversies, and Therapeutic Advances
Jiaxin Zhan ,
Hang Lei ,
Lu Gan
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1
Department of Oncology, Laboratory of Immunity, Inflammation & Cancer, The First Affiliated Hospital of Chongqing Medical University, Chongqing 400016, China,
PAR 2026 , 10(2), 47–56;
https://doi.org/10.26689/par.v10i2.14538
© 2026 by the Authors. Licensee Whioce Publishing, Singapore. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution 4.0 International License ( https://creativecommons.org/licenses/by/4.0/ )
Abstract
Breast cancer is a complex heterogeneous disease and remains one of the common malignant tumors threatening women’s health worldwide. Currently, precision therapy guided by molecular subtyping has significantly improved the prognosis of breast cancer patients. Human epidermal growth factor receptor 2 (HER2), as a critical therapeutic target for breast cancer, has long been classified into HER2-positive and HER2-negative subtypes based on expression levels [1]. With the advancement of clinical research, the classification of HER2 expression has evolved. The DESTINY-Breast04 (DB04) study was the first phase III study to demonstrate that patients with HER2-low expression derive significant survival benefit from HER2-targeted antibody-drug conjugates (ADCs) [2], thereby establishing HER2-low expression breast cancer as a novel therapeutic subtype. Despite this therapeutic breakthrough, whether HER2-low breast cancer represents an independent molecular entity or a distinct clinical subtype remains controversial. Furthermore, its prognostic implications are still debated. This review summarizes the epidemiological characteristics, biological features, heterogeneity, survival outcomes, therapeutic advances, and resistance mechanisms associated with HER2-low breast cancer, aiming to provide evidence to refine clinical recognition and optimize management strategies.
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