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HER2 Low, Ultra-low, and Novel Complementary Biomarkers: Expanding the Spectrum of HER2 Positivity in Breast Cancer

HER2 status in breast cancer is assessed to select patients eligible for targeted therapy with anti-HER2 therapies. According to the American Society of Clinical Oncology (ASCO) and College of American Pathologists (CAP), the HER2 test positivity is defined by protein overexpression (score 3+) at im...

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Autores principales: Venetis, Konstantinos, Crimini, Edoardo, Sajjadi, Elham, Corti, Chiara, Guerini-Rocco, Elena, Viale, Giuseppe, Curigliano, Giuseppe, Criscitiello, Carmen, Fusco, Nicola
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Frontiers Media S.A. 2022
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8965450/
https://www.ncbi.nlm.nih.gov/pubmed/35372498
http://dx.doi.org/10.3389/fmolb.2022.834651
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author Venetis, Konstantinos
Crimini, Edoardo
Sajjadi, Elham
Corti, Chiara
Guerini-Rocco, Elena
Viale, Giuseppe
Curigliano, Giuseppe
Criscitiello, Carmen
Fusco, Nicola
author_facet Venetis, Konstantinos
Crimini, Edoardo
Sajjadi, Elham
Corti, Chiara
Guerini-Rocco, Elena
Viale, Giuseppe
Curigliano, Giuseppe
Criscitiello, Carmen
Fusco, Nicola
author_sort Venetis, Konstantinos
collection PubMed
description HER2 status in breast cancer is assessed to select patients eligible for targeted therapy with anti-HER2 therapies. According to the American Society of Clinical Oncology (ASCO) and College of American Pathologists (CAP), the HER2 test positivity is defined by protein overexpression (score 3+) at immunohistochemistry (IHC) and/or gene amplification at in situ hybridization (ISH). The introduction of novel anti-HER2 compounds, however, is changing this paradigm because some breast cancers with lower levels of protein expression (i.e. score 1+/2+ with no gene amplification) benefited from HER2 antibody-drug conjugates (ADC). Recently, a potential for HER2 targeting in HER2 “ultra-low” (i.e. score 0 with incomplete and faint staining in ≤10% of tumor cells) and MutL-deficient estrogen receptor (estrogen receptor)-positive/HER2-negative breast cancers has been highlighted. All these novel findings are transforming the traditional dichotomy of HER2 status and have dramatically raised the expectations in this field. Still, a more aware HER2 status assessment coupled with the comprehensive characterization of the clinical and molecular features of these tumors is required. Here, we seek to provide an overview of the current state of HER2 targeting in breast cancers beyond the canonical HER2 positivity and to discuss the practical implications for pathologists and oncologists.
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spelling pubmed-89654502022-03-31 HER2 Low, Ultra-low, and Novel Complementary Biomarkers: Expanding the Spectrum of HER2 Positivity in Breast Cancer Venetis, Konstantinos Crimini, Edoardo Sajjadi, Elham Corti, Chiara Guerini-Rocco, Elena Viale, Giuseppe Curigliano, Giuseppe Criscitiello, Carmen Fusco, Nicola Front Mol Biosci Molecular Biosciences HER2 status in breast cancer is assessed to select patients eligible for targeted therapy with anti-HER2 therapies. According to the American Society of Clinical Oncology (ASCO) and College of American Pathologists (CAP), the HER2 test positivity is defined by protein overexpression (score 3+) at immunohistochemistry (IHC) and/or gene amplification at in situ hybridization (ISH). The introduction of novel anti-HER2 compounds, however, is changing this paradigm because some breast cancers with lower levels of protein expression (i.e. score 1+/2+ with no gene amplification) benefited from HER2 antibody-drug conjugates (ADC). Recently, a potential for HER2 targeting in HER2 “ultra-low” (i.e. score 0 with incomplete and faint staining in ≤10% of tumor cells) and MutL-deficient estrogen receptor (estrogen receptor)-positive/HER2-negative breast cancers has been highlighted. All these novel findings are transforming the traditional dichotomy of HER2 status and have dramatically raised the expectations in this field. Still, a more aware HER2 status assessment coupled with the comprehensive characterization of the clinical and molecular features of these tumors is required. Here, we seek to provide an overview of the current state of HER2 targeting in breast cancers beyond the canonical HER2 positivity and to discuss the practical implications for pathologists and oncologists. Frontiers Media S.A. 2022-03-15 /pmc/articles/PMC8965450/ /pubmed/35372498 http://dx.doi.org/10.3389/fmolb.2022.834651 Text en Copyright © 2022 Venetis, Crimini, Sajjadi, Corti, Guerini-Rocco, Viale, Curigliano, Criscitiello and Fusco. https://creativecommons.org/licenses/by/4.0/This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) and the copyright owner(s) are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.
spellingShingle Molecular Biosciences
Venetis, Konstantinos
Crimini, Edoardo
Sajjadi, Elham
Corti, Chiara
Guerini-Rocco, Elena
Viale, Giuseppe
Curigliano, Giuseppe
Criscitiello, Carmen
Fusco, Nicola
HER2 Low, Ultra-low, and Novel Complementary Biomarkers: Expanding the Spectrum of HER2 Positivity in Breast Cancer
title HER2 Low, Ultra-low, and Novel Complementary Biomarkers: Expanding the Spectrum of HER2 Positivity in Breast Cancer
title_full HER2 Low, Ultra-low, and Novel Complementary Biomarkers: Expanding the Spectrum of HER2 Positivity in Breast Cancer
title_fullStr HER2 Low, Ultra-low, and Novel Complementary Biomarkers: Expanding the Spectrum of HER2 Positivity in Breast Cancer
title_full_unstemmed HER2 Low, Ultra-low, and Novel Complementary Biomarkers: Expanding the Spectrum of HER2 Positivity in Breast Cancer
title_short HER2 Low, Ultra-low, and Novel Complementary Biomarkers: Expanding the Spectrum of HER2 Positivity in Breast Cancer
title_sort her2 low, ultra-low, and novel complementary biomarkers: expanding the spectrum of her2 positivity in breast cancer
topic Molecular Biosciences
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8965450/
https://www.ncbi.nlm.nih.gov/pubmed/35372498
http://dx.doi.org/10.3389/fmolb.2022.834651
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