Trial reportBreast cancer research : BCR2025
Exploring the role of ESR1 mutations in metastatic hormone receptor-positive breast cancer T cell immune surveillance disruption.
Trial report in Breast cancer research : BCR, 2025. The graph could read no effect estimate from its abstract, so it casts no vote on the map. It is linked to trial NCT02838381 (Study of Genetic and Cellular Immunological Parameters Predictive of Disease-free Survival in Patients With Metastatic Cancer), which is not on this map. Cited by 6 papers.
What it found
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The trial behind it
Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
Study of Genetic and Cellular Immunological Parameters Predictive of Disease-free Survival in Patients With Metastatic Cancer
Who cites it
6 citing papers in PubMed.
- Activating mutations in ESR1 contribute to an immunosuppressive breast tumor microenvironment by dampening cytokine secretion.JCI insight · 2026Article
- Afuresertib plus fulvestrant for pretreated HR-positive, HER2-negative, advanced breast cancer: a phase Ib trial.Nature communications · 2026Article
- Real-World Clinical Experience of First-Line Ribociclib Combined with an Aromatase Inhibitor in Metastatic Breast Cancer.Cancers · 2026Article
- Identification and validation of candidate biomarkers associated with mitochondria and 18 types of programmed cell death in trigeminal neuralgia: insights from transcriptome sequencing.Frontiers in molecular neuroscience · 2026Article
- HLA class II-restricted T cell epitopes in public neoantigens of ESR1 and PIK3CA in breast cancer.BMC cancer · 2025Article
- Efficacy and mechanism of long-snake moxibustion for treating insomnia in breast cancer survivors: study protocol for a randomized controlled trial.Frontiers in neurology · 2025Article
Corrections and comments
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Authors and funding
17 authors.
Funding
Abstract
backgroundBreast Cancer (BC) is the most common type of cancer in women around the world and 70% of cases are hormone-receptor positive (HR+). In 40% of cases, a key mechanism of endocrine resistance to the standard first line is a mutation of the ligand-binding domain (LBD) of Estrogen Receptor 1 (ESR1) encoding estrogen receptor α (ER). Most common ESR1 mutations that occur at positions 537 and 538 have been associated with poor clinical outcomes. ESR1 mutations have the potential to provide neoantigens. This study aims to identify if ESR1 mutations generate specific T cell responses against ESR1 neoantigens in patients with HR
methodsWe identified candidate ESR1-derived peptides by predictive software (SYFPEITHI and NetMHCpan 3.0). Then the immunogenicity of ESR1-derived peptides was assessed in Peripheral-Blood-Mononuclear-Cells from 31 healthy donors (HD) and 25 patients with metastatic HR-positive BC by IFN-γ ELISpot assay. A vaccination assay on a humanized mouse model (HLA-A2/DR1) was used to validate the immunogenicity and the presentation of these peptides. Finally, we used Bulk RNA-Seq sequencing along with MCPcounter, a cellular deconvolution method, to investigate the immune contexture of ESR1-mutated BC.
resultsPreliminary results showed recognition of ESR1-derived peptides by women HD lymphocytes but not in men. Frequencies and intensities of such immune responses were increased in patients with BC. Our results showed that 40% of patients had specific immune responses. In addition, we demonstrated the HLA-A2 ESR1 peptide immunogenicity in humanized HLA-A2/DR1 mice. In a data set generated from BC patients refractory to conventional therapy we showed that ESR1 mutations are correlated in advanced diseases with downregulation of molecules involved in antigen presentation and with loss HLA Class I gene expression. ESR1-mutated BC had a decrease in immune cell infiltration.
conclusionThese results support that common ESR1 mutations generate neoantigens in hormone-receptor positive metastatic breast cancers. If ESR1 peptides-restricted lymphocytes were detectable in BC patients, ESR1 mutations promote immune escape at advanced stages.
trial registrationClinicalTrials.gov, NCT02838381. Registered on June 2012.
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