Prevalence Of Treg In Breast Cancer Patients

Abstract

Background: Regulatory T cells, often defined by FOXP3 expression, are central to maintaining immune homeostasis but can be hijacked by tumors for suppressing the anti tumor immunity. For breast cancer, high intratumoral Treg densities in a case or other have been said to portend a poorer clinical outcome, though the number, its change by disease stage and molecular subtype, and methodological consistency across studies are yet to be widely characterized. Objectives: To do a systematic review and meta-analysis on the prevalence of FOXP3+ Treg in breast cancer, kind differences by tumor stage and molecular subtype, review methodological heterogeneity, and see how this relates to prognosis and therapeutic targeting. Methods: At PubMed/MEDLINE, Embase, Scopus, and Web of Science, through June 15, 2025, we searched for clinical, cross-sectional, and observational studies that quantify Tregs in adult breast cancer patients, when Tregs are enumerated or identified by immunohistochemistry, flow cytometry, or transcriptomic deconvolution. Screening and data extraction were conducted independently by two reviewers. On the fourteen immunohistochemistry studies random effects meta-analyses estimated pooled prevalence of intratumoral Tregs and subgroup effects across stage (I-II vs. III-IV) and subtype (HR+, HER2+, triple negative). They assessed heterogeneity via I² and checked for publication bias through funnel plot symmetry. Results: From 180 identified records, 28 studies fulfilled the inclusion criteria. The pooled intratumoral FOXP3+ Treg prevalence was 12.4% (95% CI: 10.1–14.7%; I² = 68%). Hence, late-stage tumors have a larger number of Tregs than the early ones (16.8% vs. 10.1%, p < 0.01), whereas the triple negatives have more Tregs than HR+ tumors (15.3% vs. 9.4%, p < 0.01). Analysis of peripheral blood was concordant with transcriptomic estimate. Funnel plots provide indications for a low or null small study effect. Variations have been caused mainly by methodological heterogeneity, especially in immunohistochemical (IHC) scoring definitions and gene signature definitions. Conclusion: Tregs are an important immunosuppressive entity in breast cancer, especially in advanced and triple-negative disease. Varied quantification methodologies prevent the inclusion of Treg density into prognostic models, which might be used to help tailor Treg-directed immunotherapies. Longitudinal and interventional investigations will then need to assess changes in Tregs over time and the clinical benefits of Treg modulation.