2026-04-13T07:06:20Zhttps://recercat.cat/oai/request

oai:recercat.cat:11351/67592024-06-06T08:38:13Zcom_2072_378070com_2072_378040col_2072_378092

00925njm 22002777a 4500 dc Cortés Castan, Javier author Blanco-Heredia, Juan author Tiezzi, Daniel G. author Gonçalves Ribeiro, Samuel author Ortega Cebrian, Vanesa author Cusco Pons, Pol author Fasani, Roberta author Nuciforo, Paolo Giovanni author Rubio Rodríguez, Isabel Teresa author Villacampa Javierre, Guillermo author Dienstmann, Rodrigo author De Mattos-Arruda, Leticia author 2022-01-11T12:01:23Z 2022-01-11T12:01:23Z 2021-06-07 Càncer de mama; Genòmica del càncer; Biomarcadors tumorals Cáncer de mama; Genómica del cáncer; Biomarcadores tumorales Breast cancer; Cancer genomics; Tumour biomarkers 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 = <0.001); neoantigen load was weakly correlated with stromal TILs (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 < 0.05). Mutational heterogeneity, subclonal architecture and the improvement of immune microenvironment along with remodelling of hypoxia and EMT may influence the response to neoadjuvant treatment. This work was supported by Cancer Research UK. L.D.M.A. was partly funded by Spanish Association against cancer. Mama - Càncer - Tractament Càncer - Aspectes genètics DISEASES::Neoplasms::Neoplasms by Site::Breast Neoplasms Other subheadings::Other subheadings::/therapy ANALYTICAL, DIAGNOSTIC AND THERAPEUTIC TECHNIQUES, AND EQUIPMENT::Therapeutics::Combined Modality Therapy::Neoadjuvant Therapy PHENOMENA AND PROCESSES::Genetic Phenomena::Genetic Variation::Mutation ENFERMEDADES::neoplasias::neoplasias por localización::neoplasias de la mama Otros calificadores::Otros calificadores::/terapia TÉCNICAS Y EQUIPOS ANALÍTICOS, DIAGNÓSTICOS Y TERAPÉUTICOS::terapéutica::tratamiento combinado::tratamiento neoadyuvante FENÓMENOS Y PROCESOS::fenómenos genéticos::variación genética::mutación The temporal mutational and immune tumour microenvironment remodelling of HER2-negative primary breast cancers