SGLT2 inhibitor use and long-term outcomes in anthracycline-treated breast cancer: A real-world retrospective cohort study.

Abstract

e12707 Background: Anthracycline-based chemotherapy remains a cornerstone of breast cancer treatment but is limited by dose-dependent cardiotoxicity. Sodium-glucose cotransporter-2 inhibitors (SGLT2i) have demonstrated cardioprotective effects across diverse populations. Preclinical models suggest they may mitigate anthracycline-induced cardiotoxicity. However, clinical data evaluating this association remain limited. Methods: We conducted a retrospective cohort study using the TriNetX real world data platform, including adults with breast cancer who received anthracycline within one year of diagnosis. Patients were stratified by SGLT2i use within one year of diagnosis into the SGLT2i group and the non-SGLT2i group. Propensity score matching (PSM) was performed to balance baseline demographics and comorbidities. Outcomes included 3-year all-cause mortality, heart failure, myocardial infarction, atrial fibrillation, mean left ventricular ejection fraction (LVEF), mean Troponin I, and mean brain natriuretic peptide level (BNP), analyzed using risk ratios (RR) and Kaplan-Meier survival analysis. Results: After PSM, 2912 patients were included in each group, with a mean follow-up of 630.3 days in SGLT2i group and 756.7 days in non-SGLT2i group. Mean age was 61.5 years vs 62.3 years (SGLT2i group vs non-SGLT2i group), with more than 98% of females in both groups. Most patients were White (49.0% in SGLT2i group and 48.6% in non-SGLT2i group), followed by African American (23.7% vs. 23.4%), unknown races (14.0% vs 14.0%), and Asian (9.5% vs. 9.8%). At baseline, the SGLT2i group had lower mean LVEF (53.4% vs 61.9%), higher mean Troponin I (0.992 vs 0.0849), and higher mean BNP levels (778 vs 240). SGLT2i group was associated with significantly lower 3-year all-cause mortality (Hazard ratio 0.52, 95% CI 0.44–0.61). Heart failure incidence (9.5% vs 6.0%; p = 0.0005) was significantly higher in the SGLT2i group. Mean LVEF in SGLT2i group was significantly lower (51.7% vs 58.9; p < 0.0001) and mean BNP level was significantly higher in SGLT2i group (685.5 vs 383.0; p = 0.0336). No significant differences were observed in myocardial infarction (3.9% vs 3.4%; p = 0.4459), atrial fibrillation (3.4% vs 4.5%; p = 0.0799), and mean troponin I (0.085 vs 0.113, p = 0.5191). Conclusions: In this real-world cohort, SGLT2i use was associated with lower 3-year all-cause mortality despite higher rates of heart failure. Notably, patients receiving SGLT2i had worse baseline cardiac function yet demonstrated more favorable trends in cardiac biomarkers, including smaller declines in LVEF, reductions in BNP, and lower mean troponin I levels, suggesting a slower progression of cardiac dysfunction. These findings support a potential cardioprotective and survival benefit of SGLT2i in patients with breast cancer receiving anthracycline therapy and warrant confirmation in future studies.