HER2-low metastatic breast cancer: molecular insights and therapeutic strategies

The identification of HER2-low metastatic breast cancer as a novel subgroup with therapeutic implications underscores the intricacies in breast cancer classification. This subset, comprising about 60% of breast cancer cases, presents a challenge due to its heterogeneous nature, characterized by varying HER2 protein expression levels. This heterogeneity complicates diagnosis and treatment decisions. The advent of trastuzumab deruxtecan (T-DXd), a second-generation antibody-drug conjugate (ADC), instills renewed hope for HER2-low breast cancer patients, having demonstrated effectiveness in clinical trials. The article also explores the evolution of HER2 testing guidelines, notably the 2023 ASCO/CAP guidelines that acknowledge the potential benefits of HER2-targeted therapies for this subgroup. In summary, this article emphasizes the significance of collaborative efforts between Pathologists and Oncologists in the era of precision medicine. It also highlights the potential for innovative, tailored therapies for HER2-low breast cancer, promising enhanced treatment outcomes and a broader range of therapeutic options.