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Life sciences · Journal article
Frontiers in Cardiovascular Medicine · October 9, 2026
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Background Non-steroidal aromatase inhibitors (NSAIs) are a cornerstone of adjuvant endocrine therapy in postmenopausal women with hormone receptor-positive (HR+) breast cancer. Given their prolonged use in an aging population with increasing cardiovascular vulnerability, we investigated whether baseline systemic immune-inflammation index (SII) and systemic inflammation response index (SIRI) could identify pretreatment immune-inflammatory susceptibility to NSAI-related early subclinical cardiac dysfunction. Methods This single-center retrospective cohort study included 269 postmenopausal women with HR + breast cancer who received letrozole or anastrozole between January 2020 and April 2024. The primary endpoint was study-defined composite cardiac dysfunction, defined as either an absolute decline in left ventricular ejection fraction (LVEF) of ≥10 percentage points from baseline or a relative increase in B-type natriuretic peptide (BNP) of ≥40% from baseline together with a follow-up BNP concentration ≥100 pg/mL. Baseline SII and SIRI were calculated from routine blood counts and analyzed as z-standardized natural log-transformed variables. Logistic regression, restricted cubic spline, receiver operating characteristic curve, decision curve, sensitivity, subgroup, and exploratory machine-learning-assisted risk-stratification analyses were performed. Results Among 269 patients, 63 (23.4%) met the criteria for study-defined composite cardiac dysfunction. In fully adjusted models, higher z-lnSII and z-lnSIRI were independently associated with the endpoint (SII: OR 2.148, 95% CI 1.540–2.997; SIRI: OR 1.927, 95% CI 1.376–2.697; both P < 0.001). Associations remained significant in medication- and partial available-case oncology-adjusted sensitivity analyses and remained directionally consistent in post hoc sensitivity analyses using progressively higher follow-up BNP thresholds of 125, 150, 200, and 400 pg/mL. In five-fold logistic prediction analyses, the AUC increased from 0.633 for the base model to 0.745 with SII, 0.733 with SIRI, and 0.745 with both markers. Conclusion Baseline SII and SIRI were independently associated with study-defined composite cardiac dysfunction during NSAI therapy and provided incremental discrimination beyond conventional clinical variables.