HER2-Low Breast Cancer: Current Landscape and Future Prospects

Yelena Shirman, Shlomit Lubovsky, Ayelet Shai

Research output: Contribution to journalReview articlepeer-review


More than 50% of breast cancers are currently defined as “Human epidermal growth factor receptor 2 (HER2) low breast cancer (BC)”, with HER2 immunohistochemistry (IHC) scores of +1 or +2 with a negative fluorescence in situ hybridization (FISH) test. In most studies that compared the clinical and biological characteristics of HER2-low BC with HER2-negative BC, HER2-low was not associated with unique clinical and molecular characteristics, and it seems that the importance of HER2 in these tumors is being a docking site for the antibody portion of antibody drug conjugates (ADCs). Current pathological methods may underestimate the proportion of BCs that express low levels of HER2 due to analytical limitations and tumor heterogeneity. In this review we summarize and contextualize the most recent literature on HER2-low breast cancers, including clinical and translational studies We also review the challenges of assessing low HER2 expression in BC and discuss the current and future therapeutic landscape for these tumors.

Original languageEnglish
Pages (from-to)605-616
Number of pages12
JournalBreast Cancer: Targets and Therapy
StatePublished - 2023
Externally publishedYes

Bibliographical note

Publisher Copyright:
© 2023 Shirman et al.


  • ERBB2 low
  • HER2 targeted therapy
  • HER2-low
  • T-DXd
  • breast cancer
  • trastuzumab
  • trastuzumab-deruxtecan

ASJC Scopus subject areas

  • Oncology


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