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Cancer Drug Resist 2022;5:[Accepted].10.20517/cdr.2022.29© The Author(s) 2022
Accepted Manuscript
Open AccessOpinion

Improving HER2 testing reproducibility in HER2-low breast cancer 

Correspondence Address: Prof. Nicola Fusco, Department of Oncology and Hemato-Oncology, University of Milan, Milan, Italy. E-mail: nicola.fusco@unimi.it

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© The Author(s) 2022. Open Access This article is licensed under a Creative Commons Attribution 4.0 International License (https://creativecommons.org/licenses/by/4.0/), which permits unrestricted use, sharing, adaptation, distribution and reproduction in any medium or format, for any purpose, even commercially, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made.

Abstract

HER2 is a well-known prognostic and predictive biomarker in breast cancer, and it is assessed by immunohistochemistry (IHC) and reflex in situ hybridization (ISH) for clinical decision-making. In particular, the HER2-positive phenotype (i.e. IHC score 3+ or score 2+ with a positive ISH) allows for the selection of patients eligible for targeted therapy with anti-HER2 drugs. Lately, novel HER2-directed antibody-drug conjugates have demonstrated significant antitumor activity in breast cancers with low levels of HER2 expression. These tumors are defined by IHC score 1+ or score 2+ without gene amplification. Both primary and acquired resistance to anti-HER2 therapies remains a challenge in the treatment of breast cancers according to the HER2 positivity continuum. Thus, the ability to precisely discriminate between HER2-negative (i.e. IHC score 0), HER2-low, and HER2-positive breast cancers is no longer a mere academic exercise. Here, we summarize the possible mechanisms of resistance to anti-HER2 agents emphasizing the need for refreshing HER2 testing criteria, guidelines, and quality controls, and highlight the best approach to overcome the main pre-analytical and analytical variables that might trouble the sensitivity and reproducibility of this test.  

Cite This Article

Sajjadi E, Venetis K, Ivanova M, Fusco N. Improving HER2 testing reproducibility in HER2-low breast cancer. Cancer Drug Resist 2022;5:[Accept]. http://dx.doi.org/10.20517/cdr.2022.29

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