Breast cancer progression in the presence of treated and untreated left ventricular dysfunction.

backgroundRecent studies have shown that heart failure (HF) and left ventricular (LV) dysfunction are associated with enhanced tumor growth. However, whether treating LV dysfunction mitigates its impact on cancer progression remains unknown. We hypothesized that HF treatments would attenuate tumor growth in a rodent model of post-myocardial infarction (MI)-induced LV dysfunction, and that different pharmacological agents (carvedilol, enalapril, and empagliflozin) might exert distinct effects on tumor progression.

methodsMI was induced in female BALB/c mice, leading to LV dysfunction. Mice with LV ejection fraction < 40% two weeks after MI received daily vehicle or one of three HF treatments by gavage. Two weeks later, 2 × 10

resultsEnalapril reversed several MI-induced transcriptomic changes in tumor tissue. Empagliflozin reduced primary tumor growth, while carvedilol reduced metastatic clusters. These effects were absent in control mice without MI, and neither drug directly affected cultured 4T1 cells. Transcriptomic analysis revealed treatment-specific inflammatory pathway regulation. Notably, carvedilol and empagliflozin restored MI-suppressed IFN-γ expression in tumors, accompanied by increased STAT1 expression in 4T1 cells.

conclusionSpecific HF treatments can mitigate cancer growth in a mouse model of MI-induced LV dysfunction, with outcomes varying by treatment. These benefits occurred only with LV dysfunction, suggesting they result from changes in HF pathophysiology rather than direct drug effects on tumor cells. Restoration of immune signaling may contribute to these effects.