Abstract Body: Introduction: Breast cancer (BC) is a malignancy that predominantly affects women and has shown high incidence and mortality rates in recent decades. Several studies have focused on the effects of anthracyclines, demonstrating their role in modulating gene and protein expression, leading to cardiotoxicity, inflammation, apoptosis, and cardiac fibrosis in individuals with BC. However, the direct impact of BC itself on cardiac gene and protein expression, in the absence of anthracycline treatment, remains poorly understood.
Aims: Therefore, the aim of this study was to evaluate the differential expression of genes and proteins in the cardiac tissue of animals with BC, in the absence of anthracycline treatment.
Methods: Twelve 12-week-old female BALB/c mice were used, including four animals without BC (control group, CG) and eight animals with BC. After euthanasia, cardiac tissue was collected for RNA extraction, and gene expression analysis was performed using RT-qPCR. Protein expression analysis was also conducted.
Results: BC animals exhibited increased expression of profibrotic genes in cardiac tissue, including TGF-β (127.8 ± 5.8% of control, p < 0.0475), COL1A1 (135.8 ± 9.2% of control, p < 0.0403), and MAPK (141.1 ± 10.6% of control, p < 0.0280) compared to the CG. A trend toward increased IL-1 expression was observed in the BC group (139.2 ± 11.2% of control, p = 0.057), whereas no significant differences were found for TNF-α (p = 0.0897) or the anti-inflammatory cytokine IL-10 (p = 0.4038).
At the protein level, increased caspase-3 expression was observed in the BC group compared to the CG (p < 0.05), along with reduced expression of NF-κB (p < 0.01), TNF-α (p < 0.01), and BCL-2 (p < 0.01). Additionally, BC animals showed reduced cardiac mass (p < 0.0424) and decreased skeletal muscle mass, including gastrocnemius (p < 0.0296) and soleus (p < 0.0028), compared to controls.
Conclusion: BC promotes cardiac remodeling characterized by fibrosis- and apoptosis-related signaling, leading to cardiac atrophy independent of anthracycline treatment. These findings highlight BC as an independent contributor to cardiac and skeletal sarcopenia and cardiovascular dysfunction.