ArticleBreast cancer research : BCR2019
Cancer-immune interactions in ER-positive breast cancers: PI3K pathway alterations and tumor-infiltrating lymphocytes.
Article in Breast cancer research : BCR, 2019. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 77 papers.
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Who cites it
77 citing papers in PubMed, 129 citations in OpenAlex.
- Trial
- Short-duration preoperative endocrine therapy alters molecular profiles to predict favourable outcome in ER+/HER2+ early breast cancer: a POETIC translational study.EBioMedicine · 2025Trial
- Combining histological grade, TILs, and the PD-1/PD-L1 pathway to identify immunogenic tumors and de-escalate radiotherapy in early breast cancer: a secondary analysis of a randomized clinical trial.Journal for immunotherapy of cancer · 2023Trial
- Integrating Tumor-Intrinsic and Immunologic Factors to Identify Immunogenic Breast Cancers from a Low-Risk Cohort: Results from the Randomized SweBCG91RT Trial.Clinical cancer research : an official journal of the American Association for Cancer Research · 2023Trial
- Molecular correlates of response to eribulin and pembrolizumab in hormone receptor-positive metastatic breast cancer.Nature communications · 2021Trial
- Tumour-infiltrating lymphocytes as a prognostic and tamoxifen predictive marker in premenopausal breast cancer: data from a randomised trial with long-term follow-up.Breast cancer research : BCR · 2020Trial
- Breast cancer immunogenicity as a spectrum: evolving concepts and therapeutic implications.The Journal of clinical investigation · 2026Review
- Article
- Estrogen promotes tumor phenotypes in ER+ and ER- breast cancer through UGDH-GPR30.JCI insight · 2026Article
- Interpretable deep neural network identifies robust biomarkers for diseases with mechanistic insights from omics data.Briefings in bioinformatics · 2026Article
- Breast cancer immunotherapy: mechanisms of immune evasion, biomarkers, and emerging therapeutic strategies.Molecular cancer · 2026Review
- Tailoring targeted therapies for younger women with ER-positive early-stage breast cancer.Nature reviews. Clinical oncology · 2026Review
- IL3RA identified as novel biomarker and therapeutic target for ERClinical proteomics · 2026Article
- Cyclin-Dependent 4/6 Kinase Inhibitors for Treatment of HER2-Positive Breast Cancer: 2026 Update.Cancers · 2026Review
- CD8+ T cells in the tumor microenvironment modulate the response to endocrine therapy in breast cancer.The Journal of clinical investigation · 2026Article
- Investigation of the pan-cancer property of SDC1 and its expression pattern affected patients' overall survival for breast cancer.Discover oncology · 2025Article
- CUEDC1 promotes glycolytic metabolism reprogramming through the CUEDC1/CACNG4/PI3K axis to promote ER-positive breast cancer growth.Cellular & molecular biology letters · 2025Article
- Molecular Subtypes and Survival Patterns in Female Breast Cancer: Insights from a 12-Year Cohort.Medicina (Kaunas, Lithuania) · 2025Article
- Hormone Receptor Positive/HER2 Negative Breast Carcinoma: Association ofInternational journal of molecular sciences · 2025Article
- Gut microbiota and breast cancer risk: a Mendelian randomization study stratified by ER status.Discover oncology · 2025Article
17 more citing papers are in PubMed but not listed here.
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Authors and funding
16 authors at 3 institutions in 3 countries.
Funding
Abstract
introductionThe presence of tumor-infiltrating lymphocytes (TILs) is correlated with good prognosis and outcome after (immuno)therapy in triple-negative and HER2-positive breast cancer. However, the role of TILs in luminal breast cancer is less clear. Emerging evidence has now demonstrated that genetic aberrations in malignant cells influence the immune landscape of tumors. Phosphatidylinositol 3-kinase (PI3K) is the most common altered pathway in ER-positive breast cancer. It is unknown whether changes in the PI3K pathway result in a different composition of the breast tumor microenvironment. Here we present the retrospective analysis of a prospective randomized trial in ER-positive breast cancer on the prognostic and predictive value of specific tumor-associated lymphocytes in the context of PI3K alterations.
methodsWe included 563 ER-positive tumors from a multicenter trial for stage I to III postmenopausal breast cancer patients, who were randomized to tamoxifen or no adjuvant therapy. The amount of CD8-, CD4-, and FOXP3-positive cells was evaluated by immunohistochemistry and quantified by imaging-analysis software. We analyzed the associations between PIK3CA hotspot mutations, PTEN expression, phosphorylated proteins of the PI3K and MAPK pathway (p-AKT, p-ERK1/2, p-4EBP1, p-p70S6K), and recurrence-free interval after adjuvant tamoxifen or no adjuvant treatment.
resultsCD8-positive lymphocytes were significantly more abundant in PIK3CA-mutated tumors (OR = 1.65; 95% CI 1.03-2.68). While CD4 and FOXP3 were not significantly associated with prognosis, patients with tumors classified as CD8-high had increased risk of recurrence (HR = 1.98; 95% CI 1.14-3.41; multivariable model including PIK3CA status, treatment arm, and other standard clinicopathological variables). Lymphocytes were more often present in tumors with increased PI3K downstream phosphorylation. This was most pronounced for FOXP3-positive cells.
conclusionThese exploratory analyses of a prospective trial in luminal breast cancer suggest high CD8 infiltration is associated with unfavorable outcome and that PI3K pathway alterations might be associated with the composition of the tumor microenvironment.
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