HER2-low breast cancer: a new biological entity or a therapeutic defnition? A current view of the problem

Background. Over the past decade, the understanding of the biology of HER2-negative breast cancer has changed signifcantly due to the identifcation of the HER2-low and HER2-ultralow categories, which have gained clinical signifcance with the advent of new-generation antibody-drug conjugates. Goal: to systematize recent data on the molecular and morphological features of this group of tumors, discuss the diagnostic diffculties associated with interpreting low levels of HER2 expression, and provide data from key clinical studies that have determined the role of ADC in the treatment of patients with HER2-low and HER2-ultralow breast cancers. Material and Methods. The literature search was conducted in Medline, Cochrane Library, and Elibrary databases, covering the period from 2004 to 2025. Conclusion. HER2-low and HER2-ultralow breast cancers represent clinically signifcant subtypes, presenting diagnostic and therapeutic challenges. Further studies are needed for refning diagnostic criteria and developing targeted therapies.