Clinical, pathological, and PAM50 gene expression features of HER2-low breast cancer

Abstract Novel antibody-drug conjugates against HER2 are showing high activity in HER2-negative breast cancer (BC) with low HER2 expression (i.e., 1+ or 2+ and lack of ERBB2 amplification). However, the clinical and molecular features of HER2-low BC are yet to be elucidated. Here, we collected retro...

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Autores principales:	Francesco Schettini, Nuria Chic, Fara Brasó-Maristany, Laia Paré, Tomás Pascual, Benedetta Conte, Olga Martínez-Sáez, Barbara Adamo, Maria Vidal, Esther Barnadas, Aranzazu Fernández-Martinez, Blanca González-Farre, Esther Sanfeliu, Juan Miguel Cejalvo, Giuseppe Perrone, Giovanna Sabarese, Francesca Zalfa, Vicente Peg, Roberta Fasani, Patricia Villagrasa, Joaquín Gavilá, Carlos H. Barrios, Ana Lluch, Miguel Martín, Mariavittoria Locci, Sabino De Placido, Aleix Prat
Formato:	article
Lenguaje:	EN
Publicado:	Nature Portfolio 2021
Materias:	Neoplasms. Tumors. Oncology. Including cancer and carcinogens RC254-282
Acceso en línea:	https://doaj.org/article/2eba3978bf5741538c429b49f4a590be
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spelling	oai:doaj.org-article:2eba3978bf5741538c429b49f4a590be2021-12-02T15:16:18ZClinical, pathological, and PAM50 gene expression features of HER2-low breast cancer10.1038/s41523-020-00208-22374-4677https://doaj.org/article/2eba3978bf5741538c429b49f4a590be2021-01-01T00:00:00Zhttps://doi.org/10.1038/s41523-020-00208-2https://doaj.org/toc/2374-4677Abstract Novel antibody-drug conjugates against HER2 are showing high activity in HER2-negative breast cancer (BC) with low HER2 expression (i.e., 1+ or 2+ and lack of ERBB2 amplification). However, the clinical and molecular features of HER2-low BC are yet to be elucidated. Here, we collected retrospective clinicopathological and PAM50 data from 3,689 patients with HER2-negative disease and made the following observations. First, the proportion of HER2-low was higher in HR-positive disease (65.4%) than triple-negative BC (TNBC, 36.6%). Second, within HR-positive disease, ERBB2 and luminal-related genes were more expressed in HER2-low than HER2 0. In contrast, no gene was found differentially expressed in TNBC according to HER2 expression. Third, within HER2-low, ERBB2 levels were higher in HR-positive disease than TNBC. Fourth, HER2-low was not associated with overall survival in HR-positive disease and TNBC. Finally, the reproducibility of HER2-low among pathologists was suboptimal. This study emphasizes the large biological heterogeneity of HER2-low BC, and the need to implement reproducible and sensitive assays to measure low HER2 expression.Francesco SchettiniNuria ChicFara Brasó-MaristanyLaia ParéTomás PascualBenedetta ConteOlga Martínez-SáezBarbara AdamoMaria VidalEsther BarnadasAranzazu Fernández-MartinezBlanca González-FarreEsther SanfeliuJuan Miguel CejalvoGiuseppe PerroneGiovanna SabareseFrancesca ZalfaVicente PegRoberta FasaniPatricia VillagrasaJoaquín GaviláCarlos H. BarriosAna LluchMiguel MartínMariavittoria LocciSabino De PlacidoAleix PratNature PortfolioarticleNeoplasms. Tumors. Oncology. Including cancer and carcinogensRC254-282ENnpj Breast Cancer, Vol 7, Iss 1, Pp 1-13 (2021)
institution	DOAJ
collection	DOAJ
language	EN
topic	Neoplasms. Tumors. Oncology. Including cancer and carcinogens RC254-282
spellingShingle	Neoplasms. Tumors. Oncology. Including cancer and carcinogens RC254-282 Francesco Schettini Nuria Chic Fara Brasó-Maristany Laia Paré Tomás Pascual Benedetta Conte Olga Martínez-Sáez Barbara Adamo Maria Vidal Esther Barnadas Aranzazu Fernández-Martinez Blanca González-Farre Esther Sanfeliu Juan Miguel Cejalvo Giuseppe Perrone Giovanna Sabarese Francesca Zalfa Vicente Peg Roberta Fasani Patricia Villagrasa Joaquín Gavilá Carlos H. Barrios Ana Lluch Miguel Martín Mariavittoria Locci Sabino De Placido Aleix Prat Clinical, pathological, and PAM50 gene expression features of HER2-low breast cancer
description	Abstract Novel antibody-drug conjugates against HER2 are showing high activity in HER2-negative breast cancer (BC) with low HER2 expression (i.e., 1+ or 2+ and lack of ERBB2 amplification). However, the clinical and molecular features of HER2-low BC are yet to be elucidated. Here, we collected retrospective clinicopathological and PAM50 data from 3,689 patients with HER2-negative disease and made the following observations. First, the proportion of HER2-low was higher in HR-positive disease (65.4%) than triple-negative BC (TNBC, 36.6%). Second, within HR-positive disease, ERBB2 and luminal-related genes were more expressed in HER2-low than HER2 0. In contrast, no gene was found differentially expressed in TNBC according to HER2 expression. Third, within HER2-low, ERBB2 levels were higher in HR-positive disease than TNBC. Fourth, HER2-low was not associated with overall survival in HR-positive disease and TNBC. Finally, the reproducibility of HER2-low among pathologists was suboptimal. This study emphasizes the large biological heterogeneity of HER2-low BC, and the need to implement reproducible and sensitive assays to measure low HER2 expression.
format	article
author	Francesco Schettini Nuria Chic Fara Brasó-Maristany Laia Paré Tomás Pascual Benedetta Conte Olga Martínez-Sáez Barbara Adamo Maria Vidal Esther Barnadas Aranzazu Fernández-Martinez Blanca González-Farre Esther Sanfeliu Juan Miguel Cejalvo Giuseppe Perrone Giovanna Sabarese Francesca Zalfa Vicente Peg Roberta Fasani Patricia Villagrasa Joaquín Gavilá Carlos H. Barrios Ana Lluch Miguel Martín Mariavittoria Locci Sabino De Placido Aleix Prat
author_facet	Francesco Schettini Nuria Chic Fara Brasó-Maristany Laia Paré Tomás Pascual Benedetta Conte Olga Martínez-Sáez Barbara Adamo Maria Vidal Esther Barnadas Aranzazu Fernández-Martinez Blanca González-Farre Esther Sanfeliu Juan Miguel Cejalvo Giuseppe Perrone Giovanna Sabarese Francesca Zalfa Vicente Peg Roberta Fasani Patricia Villagrasa Joaquín Gavilá Carlos H. Barrios Ana Lluch Miguel Martín Mariavittoria Locci Sabino De Placido Aleix Prat
author_sort	Francesco Schettini
title	Clinical, pathological, and PAM50 gene expression features of HER2-low breast cancer
title_short	Clinical, pathological, and PAM50 gene expression features of HER2-low breast cancer
title_full	Clinical, pathological, and PAM50 gene expression features of HER2-low breast cancer
title_fullStr	Clinical, pathological, and PAM50 gene expression features of HER2-low breast cancer
title_full_unstemmed	Clinical, pathological, and PAM50 gene expression features of HER2-low breast cancer
title_sort	clinical, pathological, and pam50 gene expression features of her2-low breast cancer
publisher	Nature Portfolio
publishDate	2021
url	https://doaj.org/article/2eba3978bf5741538c429b49f4a590be
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Clinical, pathological, and PAM50 gene expression features of HER2-low breast cancer

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