Identifier to cite or link to this item: http://hdl.handle.net/20.500.13003/11718
Phenotypic changes of HER2-positive breast cancer during and after dual HER2 blockade
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ISSN: 2041-1723
WOS ID: 000512537400006
Scopus EID: 2-s2.0-85078295206
PMID: 31959756
Embase PUI: L2004115032
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Braso-Maristany, Fara; Griguolo, Gaia; Pascual, Tomas; Pare, Laia; Nuciforo, Paolo; Llombart-Cussac, Antonio; Bermejo, Begona; Oliveira, Mafalda; Morales, Serafin; Martinez, Noelia; Vidal, Maria; Adamo, Barbara; Martinez, Olga; Pernas, Sonia; Lopez, Rafael; Munoz, Montserrat; Chic, Nuria; Galvan, Patricia; Garau, Isabel; Manso, Luis; Alarcon, Jesus; Martinez, Eduardo; Gregorio, Sara; Gomis, Roger R.; Villagrasa, Patricia; Cortes, Javier; Ciruelos, Eva; Prat, AleixPublication date
2020-01-20Document type
research articleCitation
Braso-Maristany F, Griguolo G, Pascual T, Pare L, Nuciforo P, Llombart-Cussac A, et al. Phenotypic changes of HER2-positive breast cancer during and after dual HER2 blockade. Nat Commun. 2020 Jan 20;11(1):385.Abstract
The HER2-enriched (HER2-E) subtype within HER2-positive (HER2+) breast cancer is highly addicted to the HER2 pathway. However, similar to 20-60% of HER2+/HER2-E tumors do not achieve a complete response following anti-HER2 therapies. Here we evaluate gene expression data before, during and after neoadjuvant treatment with lapatinib and trastuzumab in HER2+/HER2-E tumors of the PAMELA trial and breast cancer cell lines. Our results reveal that dual HER2 blockade in HER2-E disease induces a low-proliferative Luminal A phenotype both in patient's tumors and in vitro models. These biological changes are more evident in hormone receptor-positive (HR+) disease compared to HR-negative disease. Interestingly, increasing the luminal phenotype with anti-HER2 therapy increased sensitivity to CDK4/6 inhibition. Finally, discontinuation of HER2-targeted therapy in vitro, or acquired resistance to anti-HER2 therapy, leads to restoration of the original HER2-E phenotype. Our findings support the use of maintenance anti-HER2 therapy and the therapeutic exploitation of subtype switching with CDK4/6 inhibition.
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https://dx.doi.org/10.1038/s41467-019-14111-3MeSH
Breast NeoplasmsBreast
Neoadjuvant Therapy
Trastuzumab
Adult
Humans
Antineoplastic Combined Chemotherapy Protocols
Cell Line, Tumor
Lapatinib
Antineoplastic Agents, Immunological
Receptor, ErbB-2
Cell Survival
Biomarkers, Tumor
Female
Gene Expression Profiling
Treatment Outcome
Drug Resistance, Neoplasm
Biopsy
DeCS
Resistencia a AntineoplásicosAntineoplásicos Inmunológicos
Línea Celular Tumoral
Resultado del Tratamiento
Femenino
Receptor ErbB-2
Biomarcadores de Tumor
Supervivencia Celular
Terapia Neoadyuvante
Trastuzumab
Humanos
Mama
Protocolos de Quimioterapia Combinada Antineoplásica
Neoplasias de la Mama
Adulto
Perfilación de la Expresión Génica
Biopsia
Lapatinib
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Hospital Universitario Son Espases - HUSE > Comunicación científicaHospital Universitario Son Llàtzer - HUSLL > Comunicación científica