Targeted Approaches to HER2-Low Breast Cancer: Current Practice and Future Directions

SIMPLE SUMMARY: HER2-low breast cancer (BC) accounts for more than half of breast cancer patients. Anti-HER2 therapy has been ineffective in HER2-low BC, for which palliative chemotherapy is the main treatment modality. The definitive efficacy of T-Dxd in HER2-low BC breaks previous treatment strategies, which will redefine HER2-low and thus reshape anti-HER2 therapy. This review summarizes detection technologies and novel agents for HER2-low BC, and explores their possible role in future clinics, to provide ideas for the diagnosis and treatment of HER2-low BC. ABSTRACT: HER2-low breast cancer (BC) has a poor prognosis, making the development of more suitable treatment an unmet clinical need. While chemotherapy is the main method of treatment for HER2-low BC, not all patients benefit from it. Antineoplastic therapy without chemotherapy has shown promise in clinical trials and is being explored further. As quantitative detection techniques become more advanced, they assist in better defining the expression level of HER2 and in guiding the development of targeted therapies, which include directly targeting HER2 receptors on the cell surface, targeting HER2-related intracellular signaling pathways and targeting the immune microenvironment. A new anti-HER2 antibody-drug conjugate called T-DM1 has been successfully tested and found to be highly effective in clinical trials. With this progress, it could eventually be transformed from a disease without a defined therapeutic target into a disease with a defined therapeutic molecular target. Furthermore, efforts are being made to compare the sequencing and combination of chemotherapy, endocrine therapy, and HER2-targeted therapy to improve prognosis to customize the subtype of HER2 low expression precision treatment regimens. In this review, we summarize the current and upcoming treatment strategies, to achieve accurate management of HER2-low BC.