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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Detalles Bibliográficos
Autores: 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
Tipo de recurso: artículo
Estado:Versión aceptada para publicación
Fecha de publicación:2022
País:España
Institución:Universidad de Barcelona
Repositorio:Dipòsit Digital de la UB
OAI Identifier:oai:diposit.ub.edu:2445/194390
Acceso en línea:https://hdl.handle.net/2445/194390
Access Level:acceso abierto
Palabra clave:Tumors cerebrals
Metàstasi
Càncer de mama
Expressió gènica
Cèl·lules T
Brain tumors
Metastasis
Breast cancer
Gene expression
T cells
Descripción
Sumario: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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