Keywords
Molecular subtype
Antibody-drug conjugates (ADCs)
Submitted : 2026-03-15
Accepted : 2026-03-30
Published : 2026-04-14
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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