Quantitative HER2 tissue and plasma profiling predicts the activity of trastuzumab deruxtecan for breast cancer

Trastuzumab deruxtecan (T-DXd) is commonly used for treating metastatic breast cancer (MBC); however, traditional HER2 immunohistochemistry has largely failed to predict T-DXd activity. We reviewed survival outcomes and tested the reliability of multiple HER2 quantitative assays in predicting T-DXd&...

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Detalles Bibliográficos
Autores: Tarantino, Paolo, Kim, Se-Eun, Hughes, Melissa E., Kusmick, Ross J., Smith, Kalie, Brasó-Maristany, Fara, Nyein Chan, Nay Nwe, Paré Brunet, Laia, Alder, Laura, Garcia Cortes, Diana, Gomez Tejeda Zanudo, Jorge, Pereslete, Alyssa M., Noteware, Laura, Moore, Heather M., Swearingen, Amanda E. D. Van, Li, Tianyu, Gupta, Hersh, D'Amico, Olivia, Martini, Alba, Morganti, Stefania, Spindel, Jennifer, Cook, Charmaine, McLaughlin, Christine, Dvir, Kathrin, Garrido Castro, Ana C., Sammons, Sarah, Files, Janet L., Sendrick, Kerry, Buck, Simone, Dillon, Deborah, Jeselsohn, Rinath, Li, Yvonne Y., Cherniack, Andrew D., LoRusso, Patricia, Lustberg, Maryam, Vega León, Rosario, Pardo, Francisco, Davis, Justin, Mueller, Claudius, Corgiat, Brian, Curigliano, Giuseppe, Anders, Carey K., Petricoin, Emanuel F., Rimm, David L., Prat Aparicio, Aleix, Tayob, Nabihah, Lin, Nancy U., Tolaney, Sara M.
Tipo de recurso: artículo
Estado:Versión publicada
Fecha de publicación:2026
País:España
Institución:Universidad de Barcelona
Repositorio:Dipòsit Digital de la UB
OAI Identifier:oai:dnet:ubarcelona__::1e6bda4629aef6a89019494d7d30d4eb
Acceso en línea:https://hdl.handle.net/2445/229281
Access Level:acceso abierto
Palabra clave:Càncer de mama
Anticossos monoclonals
Terapèutica
Breast cancer
Monoclonal antibodies
Therapeutics
Descripción
Sumario:Trastuzumab deruxtecan (T-DXd) is commonly used for treating metastatic breast cancer (MBC); however, traditional HER2 immunohistochemistry has largely failed to predict T-DXd activity. We reviewed survival outcomes and tested the reliability of multiple HER2 quantitative assays in predicting T-DXd's performance among 191 patients with MBC. We demonstrate that T-DXd's activity varies depending on the temporal evolution of HER2 immunohistochemical expression, with the longest activity observed among patients with HER2-positive disease or maintaining HER2-low disease across primary and metastatic settings. Quantitative HER2 assessment on pre-T-DXd samples showed that time-to-next treatment progressively increased by High Sensitivity-HER2 quartiles, Reverse Phase Protein Array HER2 quartiles, HER2DX ERBB2 mRNA scores and plasma-based DNADX HER2 signature tertiles (all with log-rank p < 0.05). Conversely, HER2 immunohistochemical subtypes showed limited predictive value for clinical outcomes. Additionally, elevated TOPO1 expression was associated with worse outcomes with T-DXd in HER2-negative breast cancer, suggesting potential relevance for payload-related markers in predicting T-DXd performance.

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