The IL-1β signaling axis as a prognostic determinant in early-stage breast cancer: integrated analysis of tumor and circulating biomarkers

Background. Chronic inflammation contributes to breast cancer progression, yet the prognostic relevance of inflammatory signaling pathways in early-stage disease remains incompletely defined. Interleukin-1β (IL-1β) is a key pro-inflammatory cytokine regulated by inflammasome activation and receptor-mediated signaling. This study evaluated the clinical and prognostic significance of major IL-1β pathway components in early-stage invasive breast cancer.

Methods. A retrospective cohort of 562 patients with early-stage invasive breast cancer treated between 2018 and 2025 was analyzed. Tissue microarrays were constructed, and immunohistochemistry was used to assess intratumoral expression of caspase-1, IL-1 receptor type I (IL-1R I), IL-1 receptor type II (IL-1R II), IL-1 receptor accessory protein (IL-1RacP), and IL-1 receptor antagonist (IL-1RA). Protein expression was quantified using H-scores and dichotomized by survival-based cut-offs. Circulating IL-1β levels were measured by ELISA in a subset of patients (n = 66). Associations with clinicopathological features, disease-free survival (DFS), and breast cancer-specific survival (BCSS) were evaluated.

Results. High intratumoral caspase-1 expression was associated with favorable tumor characteristics, reduced recurrence and metastasis, and improved DFS and BCSS. In contrast, elevated IL-1R II expression correlated with disease recurrence and shorter DFS. IL-1β expression alone showed no independent prognostic significance. Combined analyses demonstrated improved outcomes in tumors with preserved caspase-1 and IL-1β expression. Circulating IL-1β levels were higher in basal-type tumors but showed limited prognostic value.

Conclusions. Prognostic effects of IL-1β signaling in early-stage breast cancer depend on inflammasome integrity and receptor regulation rather than cytokine abundance alone. Integrated pathway profiling may improve biologically meaningful prognostic stratification.