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ERBB2 mRNA Expression and Response to Ado-Trastuzumab Emtansine (T-DM1) in HER2-Positive Breast Cancer
Trastuzumab emtansine (T-DM1) is approved for the treatment of human epidermal growth factor receptor 2 (HER2)-positive (HER2+) metastatic breast cancer (BC) and for residual disease after neoadjuvant therapy; however, not all patients benefit. Here, we hypothesized that the heterogeneity in the res...
Autores principales: | , , , , , , , , , , , , , , , , , , , , , , , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
MDPI
2020
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7409149/ https://www.ncbi.nlm.nih.gov/pubmed/32674482 http://dx.doi.org/10.3390/cancers12071902 |
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author | Griguolo, Gaia Brasó-Maristany, Fara González-Farré, Blanca Pascual, Tomás Chic, Núria Saurí, Tamara Kates, Ronald Gluz, Oleg Martínez, Débora Paré, Laia Tsvetkova, Vassilena Pesantez, David Vidal, Maria Adamo, Barbara Muñoz, Montserrat Galván, Patricia Barberá, Laura Cuatrecasas, Miriam Christgen, Mathias Kreipe, Hans Monge-Escartín, Inés Villagrasa, Patricia Soy, Dolors Giarratano, Tommaso Dieci, Maria Vittoria Conte, Pierfranco Harbeck, Nadia Guarneri, Valentina Prat, Aleix |
author_facet | Griguolo, Gaia Brasó-Maristany, Fara González-Farré, Blanca Pascual, Tomás Chic, Núria Saurí, Tamara Kates, Ronald Gluz, Oleg Martínez, Débora Paré, Laia Tsvetkova, Vassilena Pesantez, David Vidal, Maria Adamo, Barbara Muñoz, Montserrat Galván, Patricia Barberá, Laura Cuatrecasas, Miriam Christgen, Mathias Kreipe, Hans Monge-Escartín, Inés Villagrasa, Patricia Soy, Dolors Giarratano, Tommaso Dieci, Maria Vittoria Conte, Pierfranco Harbeck, Nadia Guarneri, Valentina Prat, Aleix |
author_sort | Griguolo, Gaia |
collection | PubMed |
description | Trastuzumab emtansine (T-DM1) is approved for the treatment of human epidermal growth factor receptor 2 (HER2)-positive (HER2+) metastatic breast cancer (BC) and for residual disease after neoadjuvant therapy; however, not all patients benefit. Here, we hypothesized that the heterogeneity in the response seen in patients is partly explained by the levels of human epidermal growth factor receptor 2 gene (ERBB2) mRNA. We analyzed ERBB2 expression using a clinically applicable assay in formalin-fixed paraffin-embedded (FFPE) tumors (primary or metastatic) from a retrospective series of 77 patients with advanced HER2+ BC treated with T-DM1. The association of ERBB2 levels and response was further validated in 161 baseline tumors from the West German Study (WGS) Group ADAPT phase II trial exploring neoadjuvant T-DM1 and 9 in vitro BC cell lines. Finally, ERBB2 expression was explored in 392 BCs from an in-house dataset, 368 primary BCs from The Cancer Genome Atlas (TCGA) dataset and 10,071 tumors representing 33 cancer types from the PanCancer TCGA dataset. High ERBB2 mRNA was found associated with better response and progression-free survival in the metastatic setting and higher rates of pathological complete response in the neoadjuvant setting. ERBB2 expression also correlated with in vitro response to T-DM1. Finally, our assay identified 0.20–8.41% of tumors across 15 cancer types as ERBB2-high, including gastric and esophagus adenocarcinomas, urothelial carcinoma, cervical squamous carcinoma and pancreatic cancer. In particular, we identified high ERBB2 mRNA in a patient with HER2+ advanced gastric cancer who achieved a long-lasting partial response to T-DM1. Our study demonstrates that the heterogeneity in response to T-DM1 is partly explained by ERBB2 levels and provides a clinically applicable assay to be tested in future clinical trials of breast cancer and other cancer types. |
format | Online Article Text |
id | pubmed-7409149 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2020 |
publisher | MDPI |
record_format | MEDLINE/PubMed |
spelling | pubmed-74091492020-08-26 ERBB2 mRNA Expression and Response to Ado-Trastuzumab Emtansine (T-DM1) in HER2-Positive Breast Cancer Griguolo, Gaia Brasó-Maristany, Fara González-Farré, Blanca Pascual, Tomás Chic, Núria Saurí, Tamara Kates, Ronald Gluz, Oleg Martínez, Débora Paré, Laia Tsvetkova, Vassilena Pesantez, David Vidal, Maria Adamo, Barbara Muñoz, Montserrat Galván, Patricia Barberá, Laura Cuatrecasas, Miriam Christgen, Mathias Kreipe, Hans Monge-Escartín, Inés Villagrasa, Patricia Soy, Dolors Giarratano, Tommaso Dieci, Maria Vittoria Conte, Pierfranco Harbeck, Nadia Guarneri, Valentina Prat, Aleix Cancers (Basel) Article Trastuzumab emtansine (T-DM1) is approved for the treatment of human epidermal growth factor receptor 2 (HER2)-positive (HER2+) metastatic breast cancer (BC) and for residual disease after neoadjuvant therapy; however, not all patients benefit. Here, we hypothesized that the heterogeneity in the response seen in patients is partly explained by the levels of human epidermal growth factor receptor 2 gene (ERBB2) mRNA. We analyzed ERBB2 expression using a clinically applicable assay in formalin-fixed paraffin-embedded (FFPE) tumors (primary or metastatic) from a retrospective series of 77 patients with advanced HER2+ BC treated with T-DM1. The association of ERBB2 levels and response was further validated in 161 baseline tumors from the West German Study (WGS) Group ADAPT phase II trial exploring neoadjuvant T-DM1 and 9 in vitro BC cell lines. Finally, ERBB2 expression was explored in 392 BCs from an in-house dataset, 368 primary BCs from The Cancer Genome Atlas (TCGA) dataset and 10,071 tumors representing 33 cancer types from the PanCancer TCGA dataset. High ERBB2 mRNA was found associated with better response and progression-free survival in the metastatic setting and higher rates of pathological complete response in the neoadjuvant setting. ERBB2 expression also correlated with in vitro response to T-DM1. Finally, our assay identified 0.20–8.41% of tumors across 15 cancer types as ERBB2-high, including gastric and esophagus adenocarcinomas, urothelial carcinoma, cervical squamous carcinoma and pancreatic cancer. In particular, we identified high ERBB2 mRNA in a patient with HER2+ advanced gastric cancer who achieved a long-lasting partial response to T-DM1. Our study demonstrates that the heterogeneity in response to T-DM1 is partly explained by ERBB2 levels and provides a clinically applicable assay to be tested in future clinical trials of breast cancer and other cancer types. MDPI 2020-07-14 /pmc/articles/PMC7409149/ /pubmed/32674482 http://dx.doi.org/10.3390/cancers12071902 Text en © 2020 by the authors. Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (http://creativecommons.org/licenses/by/4.0/). |
spellingShingle | Article Griguolo, Gaia Brasó-Maristany, Fara González-Farré, Blanca Pascual, Tomás Chic, Núria Saurí, Tamara Kates, Ronald Gluz, Oleg Martínez, Débora Paré, Laia Tsvetkova, Vassilena Pesantez, David Vidal, Maria Adamo, Barbara Muñoz, Montserrat Galván, Patricia Barberá, Laura Cuatrecasas, Miriam Christgen, Mathias Kreipe, Hans Monge-Escartín, Inés Villagrasa, Patricia Soy, Dolors Giarratano, Tommaso Dieci, Maria Vittoria Conte, Pierfranco Harbeck, Nadia Guarneri, Valentina Prat, Aleix ERBB2 mRNA Expression and Response to Ado-Trastuzumab Emtansine (T-DM1) in HER2-Positive Breast Cancer |
title | ERBB2 mRNA Expression and Response to Ado-Trastuzumab Emtansine (T-DM1) in HER2-Positive Breast Cancer |
title_full | ERBB2 mRNA Expression and Response to Ado-Trastuzumab Emtansine (T-DM1) in HER2-Positive Breast Cancer |
title_fullStr | ERBB2 mRNA Expression and Response to Ado-Trastuzumab Emtansine (T-DM1) in HER2-Positive Breast Cancer |
title_full_unstemmed | ERBB2 mRNA Expression and Response to Ado-Trastuzumab Emtansine (T-DM1) in HER2-Positive Breast Cancer |
title_short | ERBB2 mRNA Expression and Response to Ado-Trastuzumab Emtansine (T-DM1) in HER2-Positive Breast Cancer |
title_sort | erbb2 mrna expression and response to ado-trastuzumab emtansine (t-dm1) in her2-positive breast cancer |
topic | Article |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7409149/ https://www.ncbi.nlm.nih.gov/pubmed/32674482 http://dx.doi.org/10.3390/cancers12071902 |
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