Cargando…

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...

Descripción completa

Detalles Bibliográficos
Autores principales: 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
Formato: Online Artículo Texto
Lenguaje:English
Publicado: MDPI 2020
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
_version_ 1783567998651465728
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
work_keys_str_mv AT griguologaia erbb2mrnaexpressionandresponsetoadotrastuzumabemtansinetdm1inher2positivebreastcancer
AT brasomaristanyfara erbb2mrnaexpressionandresponsetoadotrastuzumabemtansinetdm1inher2positivebreastcancer
AT gonzalezfarreblanca erbb2mrnaexpressionandresponsetoadotrastuzumabemtansinetdm1inher2positivebreastcancer
AT pascualtomas erbb2mrnaexpressionandresponsetoadotrastuzumabemtansinetdm1inher2positivebreastcancer
AT chicnuria erbb2mrnaexpressionandresponsetoadotrastuzumabemtansinetdm1inher2positivebreastcancer
AT sauritamara erbb2mrnaexpressionandresponsetoadotrastuzumabemtansinetdm1inher2positivebreastcancer
AT katesronald erbb2mrnaexpressionandresponsetoadotrastuzumabemtansinetdm1inher2positivebreastcancer
AT gluzoleg erbb2mrnaexpressionandresponsetoadotrastuzumabemtansinetdm1inher2positivebreastcancer
AT martinezdebora erbb2mrnaexpressionandresponsetoadotrastuzumabemtansinetdm1inher2positivebreastcancer
AT parelaia erbb2mrnaexpressionandresponsetoadotrastuzumabemtansinetdm1inher2positivebreastcancer
AT tsvetkovavassilena erbb2mrnaexpressionandresponsetoadotrastuzumabemtansinetdm1inher2positivebreastcancer
AT pesantezdavid erbb2mrnaexpressionandresponsetoadotrastuzumabemtansinetdm1inher2positivebreastcancer
AT vidalmaria erbb2mrnaexpressionandresponsetoadotrastuzumabemtansinetdm1inher2positivebreastcancer
AT adamobarbara erbb2mrnaexpressionandresponsetoadotrastuzumabemtansinetdm1inher2positivebreastcancer
AT munozmontserrat erbb2mrnaexpressionandresponsetoadotrastuzumabemtansinetdm1inher2positivebreastcancer
AT galvanpatricia erbb2mrnaexpressionandresponsetoadotrastuzumabemtansinetdm1inher2positivebreastcancer
AT barberalaura erbb2mrnaexpressionandresponsetoadotrastuzumabemtansinetdm1inher2positivebreastcancer
AT cuatrecasasmiriam erbb2mrnaexpressionandresponsetoadotrastuzumabemtansinetdm1inher2positivebreastcancer
AT christgenmathias erbb2mrnaexpressionandresponsetoadotrastuzumabemtansinetdm1inher2positivebreastcancer
AT kreipehans erbb2mrnaexpressionandresponsetoadotrastuzumabemtansinetdm1inher2positivebreastcancer
AT mongeescartinines erbb2mrnaexpressionandresponsetoadotrastuzumabemtansinetdm1inher2positivebreastcancer
AT villagrasapatricia erbb2mrnaexpressionandresponsetoadotrastuzumabemtansinetdm1inher2positivebreastcancer
AT soydolors erbb2mrnaexpressionandresponsetoadotrastuzumabemtansinetdm1inher2positivebreastcancer
AT giarratanotommaso erbb2mrnaexpressionandresponsetoadotrastuzumabemtansinetdm1inher2positivebreastcancer
AT diecimariavittoria erbb2mrnaexpressionandresponsetoadotrastuzumabemtansinetdm1inher2positivebreastcancer
AT contepierfranco erbb2mrnaexpressionandresponsetoadotrastuzumabemtansinetdm1inher2positivebreastcancer
AT harbecknadia erbb2mrnaexpressionandresponsetoadotrastuzumabemtansinetdm1inher2positivebreastcancer
AT guarnerivalentina erbb2mrnaexpressionandresponsetoadotrastuzumabemtansinetdm1inher2positivebreastcancer
AT prataleix erbb2mrnaexpressionandresponsetoadotrastuzumabemtansinetdm1inher2positivebreastcancer