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Title: Phenotypic changes of HER2-positive breast cancer during and after dual HER2 blockade
Author: Brasó Maristany, Fara
Griguolo, Gaia
Pascual, Tomás
Paré, Laia
Nuciforo, Paolo
Llombart Cussac, Antonio
Bermejo de las Heras, Begoña
Oliveira, Mafalda
Morales, Serafín
Martínez, Noelia
Vidal Losada, Maria Jesús
Adamo, Barbara
Martínez, Olga
Pernas, Sònia
López, Rafael
Muñoz Mateu, Montserrat
Chic, Núria
Galván, Patricia
Garau, Isabel
Manso, Luis
Alarcón, Jesús
Martínez, Eduardo
Gregorio, Sara
Gomis, Roger R.
Villagrasa, Patricia
Cortés, Javier
Ciruelos, Eva
Prat Aparicio, Aleix
Keywords: Càncer de mama
Breast cancer
Issue Date: 20-Jan-2020
Publisher: Nature Publishing Group
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 trastu- zumab 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.
Note: Reproducció del document publicat a:
It is part of: Nature Communications, 2020, vol. 11
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ISSN: 2041-1723
Appears in Collections:Articles publicats en revistes (Medicina)
Articles publicats en revistes (Institut d'lnvestigació Biomèdica de Bellvitge (IDIBELL))

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