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

In advanced HER2-positive (HER2+) breast cancer (BC), the new antibody-drug conjugate trastuzumab deruxtecan (T-DXd) is more effective compared to trastuzumab emtansine (T-DM1). However, T-DXd can have significant toxicities, and the right treatment sequence is unknown. Biomarkers to guide the use o...

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Authors: Brasó-Maristany, Fara; Griguolo, Gaia; Chic Ruché, Núria; Pascual, Tomás; Paré Brunet, Laia; Maues, Julia; Galván, Patricia; Dieci, Maria Vittoria; Miglietta, Federica; Giarratano, Tommaso; Martínez-Sáez, Olga; Marín Aguilera, Mercedes; Schettini, Francesco; Conte, Benedetta; Angelats, Laura; Vidal Losada, Maria Jesús; Adamo, Barbara; Muñoz, Montse; Sanfeliu Torres, Esther; González Farré, Blanca; Vivancos, Ana; Villagrasa, Patricia; Parker, Joel S.; Perou, Charles M.; Conte, Pierfranco; Prat Aparicio, Aleix; Guarneri, Valentina
Format: Article
Status:Accepted version
Publication date:2022
Country:España
Institution:Universidad de Barcelona
Repository:Dipòsit Digital de la UB
OAI Identifier:oai:diposit.ub.edu:2445/194390
Online Access:https://hdl.handle.net/2445/194390
Access Level:Open access
Keyword:Tumors cerebrals
Metàstasi
Càncer de mama
Expressió gènica
Cèl·lules T
Brain tumors
Metastasis
Breast cancer
Gene expression
T cells
Summary:In advanced HER2-positive (HER2+) breast cancer (BC), the new antibody-drug conjugate trastuzumab deruxtecan (T-DXd) is more effective compared to trastuzumab emtansine (T-DM1). However, T-DXd can have significant 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 pre-established 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 significantly associated with better progression-free survival (p = 0.002) and overall survival (OS; P = 0.02). These findings were independent of HER2 IHC levels, hormone receptor, age, brain metastasis and line of therapy. The HER2DX risk-score (P=.04) and the immunoglobulin (IGG) signature (P=.04) were significantly associated with OS since diagnosis. HER2DX provides prognostic and predictive information following T-DM1 in advanced HER2+ BC.

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