Validation of the HER2DX genomic test in first-line advanced HER2-positive breast cancer treated with trastuzumab, pertuzumab, and taxane

Trastuzumab, pertuzumab, and a taxane (THP) has been the standard first-line therapy for HER2+ advanced breast cancer for over a decade. With new regimens emerging, genomic tools like HER2DX may help identify patients who benefit durably from THP versus those requiring intensification. Here, baselin...

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Detalhes bibliográficos
Autores: Kubeczko, Marcin, Cobo, Sandra, Sánchez Bayona, Rodrigo, Pycinski, Bartlomiej, Soberino, Jesús, Chmielik, Ewa, Sanfeliu Torres, Esther, Rey, Maria, Pardo, Francisco, Aguirre, Ángela, Castillo, Oleguer, Lesniak, Aleksandra, Oczko-Wojciechowska, Malgorzata, Carcelero San Martin, Esther, Adamo, Barbara, Vidal Losada, Maria Jesús, Bergamino Sirvén, Milana, Maues, Julia, Villacampa, Guillermo, Paré, Laia, Villagrasa, Patricia, Ciruelos, Eva, Prat Aparicio, Aleix, Jarzab, Michal, Brasó-Maristany, Fara
Tipo de documento: artigo
Estado:Versão publicada
Data de publicação:2026
País:España
Recursos:Varias* (Consorci de Biblioteques Universitáries de Catalunya, Centre de Serveis Científics i Acadèmics de Catalunya)
Repositório:Recercat. Dipósit de la Recerca de Catalunya
OAI Identifier:oai:dnet:recercat____::ddcb189f63335fd9e8ecc5ccbb9e838b
Acesso em linha:https://hdl.handle.net/2445/229244
Access Level:Acceso aberto
Palavra-chave:Genòmica
Pronòstic mèdic
Càncer de mama
Genomics
Prognosis
Breast cancer
Descrição
Resumo:Trastuzumab, pertuzumab, and a taxane (THP) has been the standard first-line therapy for HER2+ advanced breast cancer for over a decade. With new regimens emerging, genomic tools like HER2DX may help identify patients who benefit durably from THP versus those requiring intensification. Here, baseline tumor tissue from 122 patients with HER2+ treated with THP in Poland was tested with HER2DX. A previously published Spanish real-world cohort (n = 93) was added to generate a combined cohort (n = 215). Univariable analyses were performed in the Polish cohort, and multivariable Cox and logistic regression models were applied to the combined cohort. A HER2DX metastatic prognostic score was trained on overall survival (OS) in the Spanish cohort and validated in the Polish cohort. In the Polish cohort, high ERBB2 mRNA scores were associated with significantly longer real-world progression-free survival (rwPFS) (33.8 vs. 17.9 months; hazard ratio [HR] 0.57; p = 0.022) and real-world overall survival (rwOS) (75.1 vs. 40.2; HR 0.48; p = 0.009). In the combined cohort, ERBB2 high-score tumors showed prolonged rwPFS (33.8 vs. 12.5; HR 0.50; p < 0.001) and rwOS (not reached vs. 37.1; HR 0.36; p < 0.001), and higher rwORR (84.4% vs. 52.0%; p < 0.001). Prognostic value was independent of clinical variables, including number of metastatic sites. Subgroup analyses showed particularly favorable outcomes in patients with <3 sites (median rwPFS 51.7 vs. 20.3 months). The HER2DX metastatic prognostic score outperformed ERBB2 alone in the validation cohort. In conclusion, the HER2DX ERBB2 mRNA score provides independent prognostic information in HER2+ advanced breast cancer treated with THP. The HER2DX metastatic prognostic score further improves prognostic accuracy.

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