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dc.contributorVall d'Hebron Barcelona Hospital Campus
dc.contributor.authorBrasó-Maristany, Fara
dc.contributor.authorGriguolo, Gaia
dc.contributor.authorPascual, Tomás
dc.contributor.authorParé, Laia
dc.contributor.authorNuciforo, Paolo Giovanni
dc.contributor.authorLlombart-Cussac, Antonio
dc.contributor.authorAntunes de Melo Oliveira, Ana Mafalda
dc.date.accessioned2021-09-02T09:10:32Z
dc.date.available2021-09-02T09:10:32Z
dc.date.issued2020-01-20
dc.identifier.citationBrasó-Maristany F, Griguolo G, Pascual T, Paré 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;11:385.
dc.identifier.issn2041-1723
dc.identifier.urihttp://hdl.handle.net/11351/6256
dc.descriptionBreast cancer; Gene expression; Oncology
dc.description.abstractThe HER2-enriched (HER2-E) subtype within HER2-positive (HER2+) breast cancer is highly addicted to the HER2 pathway. However, ∼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.
dc.language.isoeng
dc.publisherNature Research
dc.relation.ispartofseriesNature Communications;11
dc.rightsAttribution 4.0 International
dc.rights.urihttp://creativecommons.org/licenses/by/4.0/
dc.sourceScientia
dc.subjectMama - Càncer
dc.subjectMedicaments antineoplàstics - Ús terapèutic
dc.subject.meshBreast Neoplasms
dc.subject.meshAntineoplastic Combined Chemotherapy Protocols
dc.subject.mesh/therapeutic use
dc.titlePhenotypic changes of HER2-positive breast cancer during and after dual HER2 blockade
dc.typeinfo:eu-repo/semantics/article
dc.identifier.doi10.1038/s41467-019-14111-3
dc.subject.decsneoplasias de la mama
dc.subject.decsprotocolos de quimioterapia antineoplásica combinada
dc.subject.decs/uso terapéutico
dc.relation.publishversionhttps://doi.org/10.1038/s41467-019-14111-3
dc.type.versioninfo:eu-repo/semantics/publishedVersion
dc.audienceProfessionals
dc.contributor.organismesInstitut Català de la Salut
dc.contributor.authoraffiliation[Brasó-Maristany F] Department of Medical Oncology, Hospital Clínic de Barcelona, Carrer de Villarroel, 170, 08036 Barcelona, Spain. Translational Genomics and Targeted Therapeutics in Solid Tumors, August Pi i Sunyer Biomedical Research Institute (IDIBAPS), Carrer del Rosselló, 149-153, 08036 Barcelona, Spain. [Griguolo G] Department of Medical Oncology, Hospital Clínic de Barcelona, Carrer de Villarroel, 170, 08036 Barcelona, Spain. Translational Genomics and Targeted Therapeutics in Solid Tumors, August Pi i Sunyer Biomedical Research Institute (IDIBAPS), Carrer del Rosselló, 149-153, 08036 Barcelona, Spain. Department of Surgery, Oncology and Gastroenterology, University of Padova, Via Giustiniani, 2, 35124 Padova, Italy. Medical Oncology 2, Istituto Oncologico Veneto IRCCS, Via Gattamelata, 64, 35128 Padova, Italy. [Pascual T] Department of Medical Oncology, Hospital Clínic de Barcelona, Carrer de Villarroel, 170, 08036 Barcelona, Spain. Translational Genomics and Targeted Therapeutics in Solid Tumors, August Pi i Sunyer Biomedical Research Institute (IDIBAPS), Carrer del Rosselló, 149-153, 08036 Barcelona, Spain. SOLTI Breast Cancer Research Group, Carrer de Balmes, 115, 08008 Barcelona, Spain. [Paré L] SOLTI Breast Cancer Research Group, Carrer de Balmes, 115, 08008 Barcelona, Spain. [Nuciforo P, Oliveira M] Vall d’Hebron Hospital Universitari, Barcelona, Spain. Vall d’Hebron Institute of Oncology (VHIO), Barcelona, Spain. [Llombart-Cussac A] Hospital Universitario Arnau de Vilanova, Carrer de Sant Clement, 12, 46015 Valencia, Spain
dc.identifier.pmid31959756
dc.identifier.wos000512537400006
dc.rights.accessrightsinfo:eu-repo/semantics/openAccess


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