HER2-low breast cancers: Current insights and future directions

Semin Diagn Pathol. 2022 Sep;39(5):305-312. doi: 10.1053/j.semdp.2022.07.003. Epub 2022 Jul 9.


In light of the significant clinical benefits of novel HER2-targeting antibody-drug conjugates in advanced HER2-low expressing breast cancers in recent phases I and III clinical trials, particularly trastuzumab-deruxtecan (T-Dxd), the new "HER2-low" category in breast cancers (breast cancer with a HER2 IHC score of 1+, or 2+ without gene amplification) has gained increasing attention. In the past year, "HER2-low" breast cancers have been under active investigation by both oncologists and pathologists. In this current review, we update the recent cutting-edge research on HER2-low breast cancers, with a focus on the biology of HER2-low breast cancers, the issues on the identification of HER2-low breast cancers by immunohistochemistry in current practice of pathology, and the future directions in this emerging category in breast cancers.

Keywords: Biology; Breast cancer; HER2; HER2-low; Pathology; T-Dxd; Trastuzumab-deruxtecan.

Publication types

  • Review

MeSH terms

  • Breast Neoplasms* / genetics
  • Breast Neoplasms* / pathology
  • Female
  • Humans
  • Immunohistochemistry
  • Receptor, ErbB-2 / genetics
  • Receptor, ErbB-2 / therapeutic use


  • Receptor, ErbB-2