HER2DX ERBB2 mRNA expression in advanced HER2-positive breast cancer treated with T-DM1.

Abstract

In advanced HER2-positive (HER2+) breast cancer, the new antibody-drug conjugate trastuzumab deruxtecan is more effective compared with trastuzumab emtansine (T-DM1). However, trastuzumab deruxtecan can have considerable toxicities, and the right treatment sequence is unknown. Biomarkers to guide the use of anti-HER2 therapies beyond HER2 status are needed. Here, we evaluated if preestablished levels of ERBB2 mRNA expression according to the HER2DX standardized assay are associated with response and survival following T-DM1. In ERBB2 low, medium, and high groups, the overall response rate was 0%, 29%, and 56%, respectively (P < .001). ERBB2 mRNA was statistically significantly associated with better progression-free survival (P = .002) and overall survival (OS; P = .02). These findings were independent of HER2 immunohistochemistry (IHC) levels, hormone receptor, age, brain metastasis, and line of therapy. The HER2DX risk score (P = .04) and immunoglobulin signature (P = .04) were statistically significantly associated with overall survival since diagnosis. HER2DX provides prognostic and predictive information following T-DM1 in advanced HER2+ breast cancer.

• Authors: Fara Brasó-Maristany, Gaia Griguolo, Nuria Chic, Tomás Pascual, Laia Paré, Julia Maues, Patricia Galván, Maria Vittoria Dieci, Federica Miglietta, Tommaso Giarratano, Olga Martínez-Sáez, Mercedes Marín-Aguilera, Francesco Schettini, Benedetta Conte, Laura Angelats, Maria Vidal, Barbara Adamo, Montserrat Muñoz, Esther Sanfeliu, Blanca González, Ana Vivancos, Patricia Villagrasa, Joel S Parker, Charles M Perou, PierFranco Conte, Aleix Prat, Valentina Guarneri
• Journal: Journal of the National Cancer Institute (J Natl Cancer Inst) Vol. 115 Issue 3 Pg. 332-336 (03 09 2023) ISSN: 1460-2105 [Electronic] United States
• PMID: 36576009 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)
• Copyright: © The Author(s) 2022. Published by Oxford University Press. All rights reserved. For permissions, please email: [email protected].

Chemical References

• Ado-Trastuzumab Emtansine
• Maytansine
• Antibodies, Monoclonal, Humanized
• Trastuzumab
• Receptor, ErbB-2
• RNA, Messenger
• ERBB2 protein, human

Topics

• Humans
• Female
• Ado-Trastuzumab Emtansine (therapeutic use)
• Breast Neoplasms (drug therapy, genetics, metabolism)
• Maytansine (therapeutic use)
• Antibodies, Monoclonal, Humanized (therapeutic use)
• Trastuzumab (therapeutic use)
• Receptor, ErbB-2 (genetics, metabolism)
• RNA, Messenger (genetics)