HER2-Low Breast Cancer-Current Knowledge and Future Directions

The concept of binary classification of HER2 status has recently been challenged following the DESTINY-Breast trial data showing a clinically meaningful response to antibody-drug conjugates (ADCs) in invasive breast cancer expressing low levels of HER2. HER2-low breast cancer is defined as an immunohistochemistry (IHC) score of 1+ and 2+ without HER2 gene amplification. While HER2-low breast cancer does not represent a biological entity, it encompasses both hormone receptor-positive and triple-negative breast cancer. Differences exist between this group and HER2-null breast cancer. In this review, we provide an update on HER2-low and HER2-ultralow breast cancer, including background trial data, the evolution of HER2-low expression, current clinical guidelines, quality issues, and future directions.