Analysis of the NLRP3 inflammasome components expression in triple-negative breast cancer patients with and without BRCA1 mutations

Triple-negative breast cancer (TNBC) is an aggressive and immunogenic breast cancer subtype frequently associated with BRCA1 alterations. Inflammation and innate immune sensing pathways, including inflammasomes, play complex and context-dependent roles in tumor progression and anti-tumor immunity. However, the prognostic significance of inflammasome components in TNBC remains poorly defined. We evaluated the protein expression of key inflammasome components including NLR family pyrin domain-containing 3 (NLRP3), PYD and CARD domain-containing protein (PYCARD), caspase-1 (CASP1), and interleukin-18 (IL-18) by immunohistochemistry in tumor samples from 88 TNBC patients stratified by BRCA1 status, including pathogenic germline mutations, promoter hypermethylation, and wild-type tumors. Survival analyses were performed using Kaplan-Meier estimates and Cox proportional hazards models. Lower CASP1 expression was significantly associated with smaller tumor size (p = 0.005), whereas higher NLRP3 expression was associated with axillary lymph node metastasis (p = 0.003). No significant association was observed between inflammasome protein expression and BRCA1 mutation or promoter hypermethylation status. Importantly, low NLRP3 expression was independently associated with worse disease-free survival (DFS) (hazard ratio (HR) = 3.15, 95% confidence interval (CI) = 1.36 to 7.30, p = 0.007) and overall survival (OS) (HR = 2.63, 95% CI = 1.19 to 5.79, p = 0.01). These findings indicate that reduced NLRP3 expression is associated with unfavorable prognosis in TNBC. Although exploratory in nature, this study highlights the potential relevance of inflammasome components as prognostic biomarkers in this aggressive breast cancer subtype and warrants further validation in independent cohorts.