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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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 recurso: artículo
Estado:Versión publicada
Fecha de publicación:2026
País:España
Institución:Universidad de Oviedo (UNIOVI)
Repositorio:Dipòsit Digital de la UB
OAI Identifier:oai:dnet:ubarcelona__::d23d310c11777b97a04f2ad029e55401
Acceso en línea:https://hdl.handle.net/2445/229244
Access Level:acceso abierto
Palabra clave:Genòmica
Pronòstic mèdic
Càncer de mama
Genomics
Prognosis
Breast cancer
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spelling Validation of the HER2DX genomic test in first-line advanced HER2-positive breast cancer treated with trastuzumab, pertuzumab, and taxaneKubeczko, MarcinCobo, SandraSánchez Bayona, RodrigoPycinski, BartlomiejSoberino, JesúsChmielik, EwaSanfeliu Torres, Esther Rey, MariaPardo, FranciscoAguirre, ÁngelaCastillo, OleguerLesniak, AleksandraOczko-Wojciechowska, MalgorzataCarcelero San Martin, EstherAdamo, BarbaraVidal Losada, Maria JesúsBergamino Sirvén, MilanaMaues, JuliaVillacampa, GuillermoParé, LaiaVillagrasa, PatriciaCiruelos, EvaPrat Aparicio, AleixJarzab, MichalBrasó-Maristany, FaraGenòmicaPronòstic mèdicCàncer de mamaGenomicsPrognosisBreast cancerTrastuzumab, 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.Springer Nature2026info:eu-repo/semantics/articleinfo:eu-repo/semantics/publishedVersionapplication/pdfhttps://hdl.handle.net/2445/229244Articles publicats en revistes (Medicina)reponame:Dipòsit Digital de la UBinstname:Universidad de Oviedo (UNIOVI)InglésReproducció del document publicat a: https://doi.org/10.1038/s41523-026-00909-0npj Breast Cancer, 2026, vol. 12, num.1https://doi.org/10.1038/s41523-026-00909-0cc-by-nc-nd (c) Kubeczko, Marcin et al., 2026http://creativecommons.org/licenses/by-nc-nd/4.0/info:eu-repo/semantics/openAccessoai:dnet:ubarcelona__::d23d310c11777b97a04f2ad029e554012026-05-27T06:46:51Z
dc.title.none.fl_str_mv Validation of the HER2DX genomic test in first-line advanced HER2-positive breast cancer treated with trastuzumab, pertuzumab, and taxane
title Validation of the HER2DX genomic test in first-line advanced HER2-positive breast cancer treated with trastuzumab, pertuzumab, and taxane
spellingShingle Validation of the HER2DX genomic test in first-line advanced HER2-positive breast cancer treated with trastuzumab, pertuzumab, and taxane
Kubeczko, Marcin
Genòmica
Pronòstic mèdic
Càncer de mama
Genomics
Prognosis
Breast cancer
title_short Validation of the HER2DX genomic test in first-line advanced HER2-positive breast cancer treated with trastuzumab, pertuzumab, and taxane
title_full Validation of the HER2DX genomic test in first-line advanced HER2-positive breast cancer treated with trastuzumab, pertuzumab, and taxane
title_fullStr Validation of the HER2DX genomic test in first-line advanced HER2-positive breast cancer treated with trastuzumab, pertuzumab, and taxane
title_full_unstemmed Validation of the HER2DX genomic test in first-line advanced HER2-positive breast cancer treated with trastuzumab, pertuzumab, and taxane
title_sort Validation of the HER2DX genomic test in first-line advanced HER2-positive breast cancer treated with trastuzumab, pertuzumab, and taxane
dc.creator.none.fl_str_mv 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
author Kubeczko, Marcin
author_facet 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
author_role author
author2 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
author2_role author
author
author
author
author
author
author
author
author
author
author
author
author
author
author
author
author
author
author
author
author
author
author
author
dc.subject.none.fl_str_mv Genòmica
Pronòstic mèdic
Càncer de mama
Genomics
Prognosis
Breast cancer
topic Genòmica
Pronòstic mèdic
Càncer de mama
Genomics
Prognosis
Breast cancer
description 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.
publishDate 2026
dc.date.none.fl_str_mv 2026
dc.type.none.fl_str_mv info:eu-repo/semantics/article
info:eu-repo/semantics/publishedVersion
format article
status_str publishedVersion
dc.identifier.none.fl_str_mv https://hdl.handle.net/2445/229244
url https://hdl.handle.net/2445/229244
dc.language.none.fl_str_mv Inglés
language_invalid_str_mv Inglés
dc.relation.none.fl_str_mv Reproducció del document publicat a: https://doi.org/10.1038/s41523-026-00909-0
npj Breast Cancer, 2026, vol. 12, num.1
https://doi.org/10.1038/s41523-026-00909-0
dc.rights.none.fl_str_mv cc-by-nc-nd (c) Kubeczko, Marcin et al., 2026
http://creativecommons.org/licenses/by-nc-nd/4.0/
info:eu-repo/semantics/openAccess
rights_invalid_str_mv cc-by-nc-nd (c) Kubeczko, Marcin et al., 2026
http://creativecommons.org/licenses/by-nc-nd/4.0/
eu_rights_str_mv openAccess
dc.format.none.fl_str_mv application/pdf
dc.publisher.none.fl_str_mv Springer Nature
publisher.none.fl_str_mv Springer Nature
dc.source.none.fl_str_mv Articles publicats en revistes (Medicina)
reponame:Dipòsit Digital de la UB
instname:Universidad de Oviedo (UNIOVI)
instname_str Universidad de Oviedo (UNIOVI)
reponame_str Dipòsit Digital de la UB
collection Dipòsit Digital de la UB
repository.name.fl_str_mv
repository.mail.fl_str_mv
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score 15,81155

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