HER2-Low Breast Cancer: Advances in Personalized Therapy and Prognostic Insights

Background: HER2-low breast cancer is a distinct subtype characterized by low HER2 protein expression, accounting for nearly half of all invasive breast cancer cases. Its clinical and prognostic significance is increasingly recognized, with emerging evidence suggesting slightly better outcomes compared to HER2-negative tumors. Emerging therapies, particularly antibody-drug conjugates (ADCs), are reshaping its management.Methods: We conducted a systematic literature review (PubMed, Scopus, Web of Science; 2015–2024) using keywords like "HER2-low breast cancer" and "trastuzumab deruxtecan." A total of 85 studies were screened, with 9 included in this review.  Results: Trials such as DESTINY-Breast04 demonstrate significant survival benefits with trastuzumab deruxtecan (T-DXd) in HER2-low metastatic patients. HER2-ultralow tumors (IHC 0 with faint staining) may also respond to antibody-drug conjugates(ADCs). Second-generation ADCs and biomarker-driven combinations (e.g., with immunotherapy) show promise in ongoing trials. Conclusion: HER2-low breast cancer warrants distinct diagnostic and therapeutic strategies. Standardizing testing protocols and integrating machine learning for patient selection could optimize outcomes.