AUTHOR=Sajjadi Elham , Guerini-Rocco Elena , De Camilli Elisa , Pala Oriana , Mazzarol Giovanni , Venetis Konstantinos , Ivanova Mariia , Fusco Nicola TITLE=Pathological identification of HER2-low breast cancer: Tips, tricks, and troubleshooting for the optimal test JOURNAL=Frontiers in Molecular Biosciences VOLUME=10 YEAR=2023 URL=https://www.frontiersin.org/journals/molecular-biosciences/articles/10.3389/fmolb.2023.1176309 DOI=10.3389/fmolb.2023.1176309 ISSN=2296-889X ABSTRACT=

The introduction of novel anti-HER2 antibody-drug conjugates (ADC) for the treatment of HER2-low breast cancers has transformed the traditional dichotomy of HER2 status to an expanded spectrum. However, the identification of HER2-low (i.e., immunohistochemistry (IHC) score 1 + or IHC score 2+, without gene amplification) tumors is challenged by methodological and analytical variables that might influence the sensitivity and reproducibility of HER2 testing. To open all possible therapeutic opportunities for HER2-low breast cancer patients the implementation of more accurate and reproducible testing strategies is mandatory. Here, we provide an overview of the existing barriers that may trouble HER2-low identification in breast cancer and discuss practical solutions that could enhance HER-low assessment.