2. Academic Validation
  3. Breast cancer progression in the presence of treated and untreated left ventricular dysfunction

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

  • Cardiooncology. 2025 Nov 13;11(1):106. doi: 10.1186/s40959-025-00400-y.
Celine Civati 1,  B K Goovaerts 2,  S Van Laere 3,  S Van den Bogaert 4,  J Ott 5,  B van Berlo 6,  V F M Segers # 7 8,  G W De Keulenaer # 9 10
Affiliations

Affiliations

  • 1 Laboratory of PhysioPharmacology, University of Antwerp, Antwerp, Belgium. [email protected].
  • 2 Laboratory of PhysioPharmacology, University of Antwerp, Antwerp, Belgium. [email protected].
  • 3 Center for Oncological Research, University of Antwerp, Antwerp, Belgium. [email protected].
  • 4 Laboratory of PhysioPharmacology, University of Antwerp, Antwerp, Belgium. [email protected].
  • 5 Laboratory of Cell Biology and Histology, University of Antwerp, Antwerp, Belgium. [email protected].
  • 6 Laboratory of PhysioPharmacology, University of Antwerp, Antwerp, Belgium. [email protected].
  • 7 Laboratory of PhysioPharmacology, University of Antwerp, Antwerp, Belgium. [email protected].
  • 8 Department of Cardiology, University Hospital Antwerp, Antwerp, Belgium. [email protected].
  • 9 Laboratory of PhysioPharmacology, University of Antwerp, Antwerp, Belgium. [email protected].
  • 10 Department of Cardiology, ZNA Hospital, Antwerp, Belgium. [email protected].
  • # Contributed equally.
PMID: 41233850 DOI: 10.1186/s40959-025-00400-y
Abstract

Background: Recent 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.

Methods: MI 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 × 105 4T1 metastatic breast Cancer cells were injected, with a three-week follow-up. The effects of HF treatments on Cancer progression were assessed by analyzing: (i) tumor size in vivo over 22 days, (ii) lung metastasis development and (iii) gene expression levels in tumor tissue by RNA Sequencing.

Results: Enalapril 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.

Conclusion: Specific 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.

Keywords

Breast cancer; Heart failure treatment; LV dysfunction; Reversed cardio-oncology.

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