Dr Feldman on the Significance of the HER2-Low Classification in HER2+ Breast Cancer

Sheldon M. Feldman, MD, chief, Division of Breast Surgery and Breast Surgical Oncology, director, Breast Cancer Services, professor, Department of Surgery, Montefiore Einstein, discusses the significance of the new classification of HER2-low breast cancer and how this assists with tailoring treatment approaches for patients with HER2-positive breast cancer.

The use of targeted therapies, particularly anti-HER2 agents, is gaining momentum in treating patients with advanced, stage IV cancer, especially those who have not responded to other treatments, Feldman begins. Traditionally, HER2 status in cancer cells was classified as either overexpressed, amplified, or not expressed/amplified. However, the recognition of a HER2-low category represents a significant advancement in oncology, he reports. Patients in this group, previously classified as HER2–non-overexpressed, are now found to benefit from anti-HER2 therapy, Feldman explains. One such therapy, fam-trastuzumab deruxtecan-nxki (Enhertu; T-DXd), is proving to be highly effective in this subgroup and is seen as a breakthrough for patients with advanced cancer who have exhausted other treatment options, he notes.

Feldman says this reclassification of HER2 status expands treatment eligibility, allowing HER2-low patients to access therapies previously considered unsuitable. The efficacy of T-DXd in this setting underscores the importance of this development, offering a new therapeutic avenue for patients who would not have qualified for treatment with this agent under the previous HER2 criteria. The drug’s success demonstrates the potential of refining cancer treatment by targeting specific biological markers, he emphasizes.

Broadly, the approach of identifying and targeting specific molecular drivers of cancer is pivotal in modern oncology, Feldman expands. When a therapy targets a molecular abnormality responsible for driving cancer cell growth, it can arrest disease progression and potentially lead to a cure, he adds, stating that scientific advancements are accelerating the discovery of such targets, marking substantial progress in reducing breast cancer mortality. As new targets are identified, treatment options expand, transforming cancer therapy and bringing hope to patients previously without effective options. The rapid pace of research in this area is instrumental in achieving better outcomes and advancing cancer treatment, Feldman concludes.