Molecular characteristics and advances in precision therapeutics for HR-positive and HER2-low breast cancer

HR-positive HER2-low-expressing breast cancer is a unique subtype that has been refined from the traditional HER2 binary classification system in recent years, accounting for nearly 60% of the overall incidence of breast cancer. It has significant value for precise diagnosis and treatment research. This review systematically elaborates on the epidemiological characteristics, biological basis, diagnostic technology progress, and treatment strategy evolution of this subtype. HR-positive HER2-low-expressing breast cancer is characterized by the dominance of the estrogen receptor pathway and the core molecular feature of the intersection of HER2 low-expression signals. Its diagnosis requires a balance between the fundamental role of endocrine therapy and the precise screening of anti-HER2 targeted therapy. In terms of diagnosis, the initial screening by immunohistochemistry combined with fluorescence in situ hybridization has formed a standardized process. The integration of digital pathology, next-generation sequencing, and circulating tumor DNA in liquid biopsy technologies has effectively improved diagnostic accuracy and dynamic monitoring capabilities. In terms of treatment, endocrine therapy is the cornerstone, and the CDK4/6 inhibitor combination regimen is the standard for advanced first-line treatment. Antibody-drug conjugates, especially deruxtecan, have significantly improved patient prognosis and reshaped the treatment landscape. In summary, HR-positive HER2-low-expressing breast cancer has entered the era of individualized precise treatment guided by molecular typing. In the future, further exploration of new biomarkers, optimization of combination therapy strategies, and high-quality clinical research are needed to continuously improve patient survival outcomes.