Pathological identification of HER2-low breast cancer: Tips, tricks, and troubleshooting for the optimal test

Elham Sajjadi; Elena Guerini-Rocco; Elisa De Camilli; Oriana Pala; Giovanni Mazzarol; Konstantinos Venetis; Mariia Ivanova; Nicola Fusco

doi:10.3389/fmolb.2023.1176309

Pathological identification of HER2-low breast cancer: Tips, tricks, and troubleshooting for the optimal test

Front Mol Biosci. 2023 Apr 3:10:1176309. doi: 10.3389/fmolb.2023.1176309. eCollection 2023.

Authors

Elham Sajjadi^{1

2}, Elena Guerini-Rocco^{1

2}, Elisa De Camilli², Oriana Pala², Giovanni Mazzarol², Konstantinos Venetis², Mariia Ivanova², Nicola Fusco^{1

2}

Affiliations

¹ Department of Oncology and Hemato-Oncology, University of Milan, Milan, Italy.
² Division of Pathology, IEO, European Institute of Oncology IRCCS, Milan, Italy.

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.

Keywords: HER2; HER2-low; breast cancer; immunohistochemistry; in situ hybridization; pathology; precision medicine.

Publication types

Review

Grants and funding

This work was partially supported by the Italian Ministry of Health with Ricerca Corrente 5 x 1,000 funds. MI was supported by Fondazione Umberto Veronesi; KV was supported by Fondazione IEO—MONZINO.