<i>ERBB2</i> 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...
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| Format: | Article |
| Language: | English |
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MDPI AG
2020-07-01
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| Series: | Cancers |
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| Online Access: | https://www.mdpi.com/2072-6694/12/7/1902 |
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| author | Gaia Griguolo Fara Brasó-Maristany Blanca González-Farré Tomás Pascual Núria Chic Tamara Saurí Ronald Kates Oleg Gluz Débora Martínez Laia Paré Vassilena Tsvetkova David Pesantez Maria Vidal Barbara Adamo Montserrat Muñoz Patricia Galván Laura Barberá Miriam Cuatrecasas Mathias Christgen Hans Kreipe Inés Monge-Escartín Patricia Villagrasa Dolors Soy Tommaso Giarratano Maria Vittoria Dieci Pierfranco Conte Nadia Harbeck Valentina Guarneri Aleix Prat |
| author_facet | Gaia Griguolo Fara Brasó-Maristany Blanca González-Farré Tomás Pascual Núria Chic Tamara Saurí Ronald Kates Oleg Gluz Débora Martínez Laia Paré Vassilena Tsvetkova David Pesantez Maria Vidal Barbara Adamo Montserrat Muñoz Patricia Galván Laura Barberá Miriam Cuatrecasas Mathias Christgen Hans Kreipe Inés Monge-Escartín Patricia Villagrasa Dolors Soy Tommaso Giarratano Maria Vittoria Dieci Pierfranco Conte Nadia Harbeck Valentina Guarneri Aleix Prat |
| author_sort | Gaia Griguolo |
| collection | DOAJ |
| 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 <i>(ERBB2)</i> mRNA. We analyzed <i>ERBB2</i> 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 <i>ERBB2</i> 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, <i>ERBB2</i> 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 <i>ERBB2</i> 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. <i>ERBB2</i> 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 <i>ERBB2</i>-high, including gastric and esophagus adenocarcinomas, urothelial carcinoma, cervical squamous carcinoma and pancreatic cancer. In particular, we identified high <i>ERBB2</i> 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 <i>ERBB2</i> levels and provides a clinically applicable assay to be tested in future clinical trials of breast cancer and other cancer types. |
| first_indexed | 2024-03-10T18:28:36Z |
| format | Article |
| id | doaj.art-5e92b9c883604e328d1f5c085e32f731 |
| institution | Directory Open Access Journal |
| issn | 2072-6694 |
| language | English |
| last_indexed | 2024-03-10T18:28:36Z |
| publishDate | 2020-07-01 |
| publisher | MDPI AG |
| record_format | Article |
| series | Cancers |
| spelling | doaj.art-5e92b9c883604e328d1f5c085e32f7312023-11-20T06:46:10ZengMDPI AGCancers2072-66942020-07-01127190210.3390/cancers12071902<i>ERBB2</i> mRNA Expression and Response to Ado-Trastuzumab Emtansine (T-DM1) in HER2-Positive Breast CancerGaia Griguolo0Fara Brasó-Maristany1Blanca González-Farré2Tomás Pascual3Núria Chic4Tamara Saurí5Ronald Kates6Oleg Gluz7Débora Martínez8Laia Paré9Vassilena Tsvetkova10David Pesantez11Maria Vidal12Barbara Adamo13Montserrat Muñoz14Patricia Galván15Laura Barberá16Miriam Cuatrecasas17Mathias Christgen18Hans Kreipe19Inés Monge-Escartín20Patricia Villagrasa21Dolors Soy22Tommaso Giarratano23Maria Vittoria Dieci24Pierfranco Conte25Nadia Harbeck26Valentina Guarneri27Aleix Prat28Division of Medical Oncology 2, Istituto Oncologico Veneto IOV—IRCCS, 35128 Padova, ItalyDepartment of Medical Oncology, Hospital Clínic de Barcelona, 08036 Barcelona, SpainTranslational Genomics and Targeted Therapeutics in Solid Tumors, August Pi i Sunyer Biomedical Research Institute (IDIBAPS), 08036 Barcelona, SpainDepartment of Medical Oncology, Hospital Clínic de Barcelona, 08036 Barcelona, SpainDepartment of Medical Oncology, Hospital Clínic de Barcelona, 08036 Barcelona, SpainDepartment of Medical Oncology, Hospital Clínic de Barcelona, 08036 Barcelona, SpainThe West German Study Group, 41061 Mönchengladbach, GermanyThe West German Study Group, 41061 Mönchengladbach, GermanyDepartment of Medical Oncology, Hospital Clínic de Barcelona, 08036 Barcelona, SpainSOLTI breast cancer cooperative group, 08008 Barcelona, SpainDepartment of Surgery, Oncology and Gastroenterology, University of Padova, 35124 Padova, ItalyDepartment of Medical Oncology, Hospital Clínic de Barcelona, 08036 Barcelona, SpainDepartment of Medical Oncology, Hospital Clínic de Barcelona, 08036 Barcelona, SpainDepartment of Medical Oncology, Hospital Clínic de Barcelona, 08036 Barcelona, SpainDepartment of Medical Oncology, Hospital Clínic de Barcelona, 08036 Barcelona, SpainDepartment of Medical Oncology, Hospital Clínic de Barcelona, 08036 Barcelona, SpainDepartment of Medical Oncology, Hospital Clínic de Barcelona, 08036 Barcelona, SpainDepartment of Pathology, Hospital Clínic de Barcelona, 08036 Barcelona, SpainMedical School Hannover, Institute of Pathology, 30625 Hannover, GermanyMedical School Hannover, Institute of Pathology, 30625 Hannover, GermanyPharmacy Department, Division of Medicines, Hospital Clínic de Barcelona, 08036 Barcelona, SpainSOLTI breast cancer cooperative group, 08008 Barcelona, SpainPharmacy Department, Division of Medicines, Hospital Clínic de Barcelona, 08036 Barcelona, SpainDivision of Medical Oncology 2, Istituto Oncologico Veneto IOV—IRCCS, 35128 Padova, ItalyDivision of Medical Oncology 2, Istituto Oncologico Veneto IOV—IRCCS, 35128 Padova, ItalyDivision of Medical Oncology 2, Istituto Oncologico Veneto IOV—IRCCS, 35128 Padova, ItalyBreast Center, Department of Gynecology and Obstetrics, University of Munich (LMU) and CCCLMU, 80337 Munich, GermanyDivision of Medical Oncology 2, Istituto Oncologico Veneto IOV—IRCCS, 35128 Padova, ItalyDepartment of Medical Oncology, Hospital Clínic de Barcelona, 08036 Barcelona, SpainTrastuzumab 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 <i>(ERBB2)</i> mRNA. We analyzed <i>ERBB2</i> 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 <i>ERBB2</i> 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, <i>ERBB2</i> 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 <i>ERBB2</i> 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. <i>ERBB2</i> 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 <i>ERBB2</i>-high, including gastric and esophagus adenocarcinomas, urothelial carcinoma, cervical squamous carcinoma and pancreatic cancer. In particular, we identified high <i>ERBB2</i> 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 <i>ERBB2</i> levels and provides a clinically applicable assay to be tested in future clinical trials of breast cancer and other cancer types.https://www.mdpi.com/2072-6694/12/7/1902<i>ERBB2</i> mRNAHER2-positive breast cancerT-DM1antibody-drug conjugates |
| spellingShingle | Gaia Griguolo Fara Brasó-Maristany Blanca González-Farré Tomás Pascual Núria Chic Tamara Saurí Ronald Kates Oleg Gluz Débora Martínez Laia Paré Vassilena Tsvetkova David Pesantez Maria Vidal Barbara Adamo Montserrat Muñoz Patricia Galván Laura Barberá Miriam Cuatrecasas Mathias Christgen Hans Kreipe Inés Monge-Escartín Patricia Villagrasa Dolors Soy Tommaso Giarratano Maria Vittoria Dieci Pierfranco Conte Nadia Harbeck Valentina Guarneri Aleix Prat <i>ERBB2</i> mRNA Expression and Response to Ado-Trastuzumab Emtansine (T-DM1) in HER2-Positive Breast Cancer Cancers <i>ERBB2</i> mRNA HER2-positive breast cancer T-DM1 antibody-drug conjugates |
| title | <i>ERBB2</i> mRNA Expression and Response to Ado-Trastuzumab Emtansine (T-DM1) in HER2-Positive Breast Cancer |
| title_full | <i>ERBB2</i> mRNA Expression and Response to Ado-Trastuzumab Emtansine (T-DM1) in HER2-Positive Breast Cancer |
| title_fullStr | <i>ERBB2</i> mRNA Expression and Response to Ado-Trastuzumab Emtansine (T-DM1) in HER2-Positive Breast Cancer |
| title_full_unstemmed | <i>ERBB2</i> mRNA Expression and Response to Ado-Trastuzumab Emtansine (T-DM1) in HER2-Positive Breast Cancer |
| title_short | <i>ERBB2</i> mRNA Expression and Response to Ado-Trastuzumab Emtansine (T-DM1) in HER2-Positive Breast Cancer |
| title_sort | i erbb2 i mrna expression and response to ado trastuzumab emtansine t dm1 in her2 positive breast cancer |
| topic | <i>ERBB2</i> mRNA HER2-positive breast cancer T-DM1 antibody-drug conjugates |
| url | https://www.mdpi.com/2072-6694/12/7/1902 |
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