The temporal mutational and immune tumour microenvironment remodelling of HER2-negative primary breast cancers
| Autor: | Daniel Guimarães Tiezzi, Juan Blanco-Heredia, Guillermo Villacampa, Paolo Nuciforo, Carlos Caldas, Rodrigo Dienstmann, Patricia Villagrasa, Pol Cusco, Carla A. Souza, Suet-Feung Chin, Roberta Fasani, Isabel T. Rubio, Aleix Prat, Vanesa Ortega, Javier Cortes, Samuel Gonçalves-Ribeiro, Leticia De Mattos-Arruda, Laia Paré, Stephen John Sammut, Jose Perez-Garcia |
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| Přispěvatelé: | De Mattos-Arruda, Leticia [0000-0002-4992-3645], Cortes, Javier [0000-0001-7623-1583], Tiezzi, Daniel G [0000-0002-2660-0093], Gonçalves-Ribeiro, Samuel [0000-0002-0261-3965], Chin, Suet-Feung [0000-0001-5697-1082], Prat, Aleix [0000-0003-2377-540X], Caldas, Carlos [0000-0003-3547-1489], Apollo - University of Cambridge Repository, Tiezzi, Daniel G. [0000-0002-2660-0093], Institut Català de la Salut, [De Mattos-Arruda L] IrsiCaixa, Germans Trias i Pujol University Hospital, Badalona, Spain. Germans Trias i Pujol Research Institute (IGTP), Badalona, Spain. Cancer Research UK Cambridge Institute, Robinson Way, Cambridge, UK. [Cortes J] Oncology Department International Breast Cancer Center (IBCC), Quiron Group, Barcelona, Spain. Medica Scientia Innovation Research (MedSIR), Barcelona, Spain. Medica Scientia Innovation Research (MedSIR), Ridgewood, NJ, USA. Breast Cancer Research program, Vall d’Hebron Institute of Oncology (VHIO), Barcelona, Spain. Universidad Europea de Madrid, Faculty of Biomedical and Health Sciences, Department of Medicine, Madrid, Spain. [Blanco-Heredia J] IrsiCaixa, Germans Trias i Pujol University Hospital, Badalona, Spain. Germans Trias i Pujol Research Institute (IGTP), Badalona, Spain. [Tiezzi DG] Cancer Research UK Cambridge Institute, Robinson Way, Cambridge, UK. Breast Disease Division, Ribeirão Preto School of Medicine, University of São Paulo, São Paulo, Brazil. [Villacampa G, Gonçalves-Ribeiro S, Cusco P, Fasani R, Dienstmann R, Nuciforo P, Rubio IT] Vall d’Hebron Institute of Oncology (VHIO), Barcelona, Spain. Vall d’Hebron Hospital Universitari, Barcelona, Spain. [Ortega V] Breast Cancer Research program, Vall d’Hebron Institute of Oncology (VHIO), Barcelona, Spain, Vall d'Hebron Barcelona Hospital Campus |
| Jazyk: | angličtina |
| Rok vydání: | 2021 |
| Předmět: |
0301 basic medicine
Neoplasms::Neoplasms by Site::Breast Neoplasms [DISEASES] medicine.medical_treatment 32 Biomedical and Clinical Sciences medicine.disease_cause Càncer - Aspectes genètics 631/67/1857 Tumour biomarkers chemistry.chemical_compound 0302 clinical medicine Cancer genomics 2.1 Biological and endogenous factors Pharmacology (medical) Otros calificadores::/terapia [Otros calificadores] Neoadjuvant therapy RC254-282 Cancer 2 Aetiology neoplasias::neoplasias por localización::neoplasias de la mama [ENFERMEDADES] Mutation article Neoplasms. Tumors. Oncology. Including cancer and carcinogens 3 Good Health and Well Being HORMÔNIOS 3204 Immunology Therapeutics::Combined Modality Therapy::Neoadjuvant Therapy [ANALYTICAL DIAGNOSTIC AND THERAPEUTIC TECHNIQUES AND EQUIPMENT] Oncology 030220 oncology & carcinogenesis Eribulin Stromal cell Genetic Phenomena::Genetic Variation::Mutation [PHENOMENA AND PROCESSES] 631/67/69 03 medical and health sciences Immune system Breast cancer Downregulation and upregulation Breast Cancer medicine Genetics Radiology Nuclear Medicine and imaging Epithelial–mesenchymal transition fenómenos genéticos::variación genética::mutación [FENÓMENOS Y PROCESOS] business.industry Other subheadings::/therapy [Other subheadings] 631/67/1347 medicine.disease 3211 Oncology and Carcinogenesis 030104 developmental biology chemistry FOS: Biological sciences Mama - Càncer - Tractament Cancer research terapéutica::tratamiento combinado::tratamiento neoadyuvante [TÉCNICAS Y EQUIPOS ANALÍTICOS DIAGNÓSTICOS Y TERAPÉUTICOS] business |
| Zdroj: | npj Breast Cancer, Vol 7, Iss 1, Pp 1-10 (2021) Repositório Institucional da USP (Biblioteca Digital da Produção Intelectual) Universidade de São Paulo (USP) instacron:USP NPJ Breast Cancer Scientia |
| ISSN: | 2374-4677 |
| Popis: | The biology of breast cancer response to neoadjuvant therapy is underrepresented in the literature and provides a window-of-opportunity to explore the genomic and microenvironment modulation of tumours exposed to therapy. Here, we characterised the mutational, gene expression, pathway enrichment and tumour-infiltrating lymphocytes (TILs) dynamics across different timepoints of 35 HER2-negative primary breast cancer patients receiving neoadjuvant eribulin therapy (SOLTI-1007 NEOERIBULIN-NCT01669252). Whole-exome data (N = 88 samples) generated mutational profiles and candidate neoantigens and were analysed along with RNA-Nanostring 545-gene expression (N = 96 samples) and stromal TILs (N = 105 samples). Tumour mutation burden varied across patients at baseline but not across the sampling timepoints for each patient. Mutational signatures were not always conserved across tumours. There was a trend towards higher odds of response and less hazard to relapse when the percentage of subclonal mutations was low, suggesting that more homogenous tumours might have better responses to neoadjuvant therapy. Few driver mutations (5.1%) generated putative neoantigens. Mutation and neoantigen load were positively correlated (R2 = 0.94, p = R2 = 0.16, p = 0.02). An enrichment in pathways linked to immune infiltration and reduced programmed cell death expression were seen after 12 weeks of eribulin in good responders. VEGF was downregulated over time in the good responder group and FABP5, an inductor of epithelial mesenchymal transition (EMT), was upregulated in cases that recurred (p |
| Databáze: | OpenAIRE |
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