Phenotypic changes of HER2-positive breast cancer during and after dual HER2 blockade

Fara Brasó-Maristany, Gaia Griguolo, Tomás Pascual, Laia Paré, Paolo Nuciforo, Antonio Llombart-Cussac, Begoña Bermejo, Mafalda Oliveira, Serafín Morales, Noelia Martínez, Maria Vidal, Barbara Adamo, Olga Martínez, Sonia Pernas, Rafael López, Montserrat Muñoz, Núria Chic, Patricia Galván, Isabel Garau, Luis Manso, Jesús Alarcón, Eduardo Martínez, Sara Gregorio, Roger R. Gomis, Patricia Villagrasa, Javier Cortés, Eva Ciruelos and Aleix Prat ()
Additional contact information
Fara Brasó-Maristany: Hospital Clínic de Barcelona
Gaia Griguolo: Hospital Clínic de Barcelona
Tomás Pascual: Hospital Clínic de Barcelona
Laia Paré: SOLTI Breast Cancer Research Group
Paolo Nuciforo: Vall d’Hebrón University Hospital
Antonio Llombart-Cussac: Hospital Universitario Arnau de Vilanova
Begoña Bermejo: Hospital Clínico Universitario de Valencia
Mafalda Oliveira: Vall d’Hebrón University Hospital
Serafín Morales: Hospital Universitario Arnau de Vilanova
Noelia Martínez: Hospital Universitario Ramón y Cajal
Maria Vidal: Hospital Clínic de Barcelona
Barbara Adamo: Hospital Clínic de Barcelona
Olga Martínez: Hospital Clínic de Barcelona
Sonia Pernas: SOLTI Breast Cancer Research Group
Rafael López: Hospital Clínico Universitario de Santiago, Rúa da Choupana, s/n
Montserrat Muñoz: Hospital Clínic de Barcelona
Núria Chic: Hospital Clínic de Barcelona
Patricia Galván: Hospital Clínic de Barcelona
Isabel Garau: Hospital Son Llàtzer, Ctra. de Manacor
Luis Manso: Hospital Universitario 12 de Octubre, Av. de Córdoba, s/n
Jesús Alarcón: Hospital Universitario Son Espases
Eduardo Martínez: Consorcio Hospitalario Provincial de Castellón
Sara Gregorio: Institute for Research in Biomedicine
Roger R. Gomis: Institute for Research in Biomedicine
Patricia Villagrasa: SOLTI Breast Cancer Research Group
Javier Cortés: Vall d´Hebron Institute of Oncology (VHIO)
Eva Ciruelos: SOLTI Breast Cancer Research Group
Aleix Prat: Hospital Clínic de Barcelona

Nature Communications, 2020, vol. 11, issue 1, 1-11

Abstract: Abstract The 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.

Date: 2020
References: Add references at CitEc
Citations:

Downloads: (external link)
https://www.nature.com/articles/s41467-019-14111-3 Abstract (text/html)

Related works:
This item may be available elsewhere in EconPapers: Search for items with the same title.

Export reference: BibTeX RIS (EndNote, ProCite, RefMan) HTML/Text

Persistent link: https://EconPapers.repec.org/RePEc:nat:natcom:v:11:y:2020:i:1:d:10.1038_s41467-019-14111-3

Ordering information: This journal article can be ordered from
https://www.nature.com/ncomms/

DOI: 10.1038/s41467-019-14111-3

Access Statistics for this article

Nature Communications is currently edited by Nathalie Le Bot, Enda Bergin and Fiona Gillespie

More articles in Nature Communications from Nature
Bibliographic data for series maintained by Sonal Shukla () and Springer Nature Abstracting and Indexing ().