Background: Breast cancer remains a leading cause of death by cancer worldwide. It is commonly accepted that angiogenesis and the expression of angiogenic factors such as vascular endothelial growth factor-A (VEGF-A) is associated with the increased risk of metastasis and poor patient outcome.Objective: This work aimed to evaluate the effects of long-term exercise training on the growth and vascularization of mammary tumors in a rat model. Materials and methods:Fifty female Sprague-Dawley rats were divided into four groups: two N-methyl-N-nitrosourea (MNU)-exposed groups (exercised and sedentary) and two control groups (exercised and sedentary). MNU was administered once, intraperitoneally at 7 weeks-old. Animals were then exercised on a treadmill for 35 weeks. Mammary tumors were evaluated using thermography, ultrasonography [Power Doppler (PDI), B Flow and contrast-enhanced ultrasound (CEUS)], and immunohistochemistry (VEGF-A).Results: Both, MNU sedentary and exercised groups showed 100% of tumor incidence, but exercised animals showed less tumors with an increased latency period. Exercise training also enhanced VEGF-A immunoexpression and vascularization (microvessel density, MVD) (p < 0.05), and reduced histological aggressiveness. Ultrasound and 2 -thermal imaging analysis confirmed the enhanced vascularization of tumors on exercised animals.Conclusion: Long-term exercise training increased VEGF-A expression, leading to enhanced tumor vascularization and reduced tumor burden, multiplicity and histological aggressiveness.

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cited for treatment d/c similar to the pivotal phase 3 trial. The proportion of d/cs due to patient requests was smaller in the RW than in the trial (6.3% vs 13.6%); disease related symptoms/clinical deterioration were similar (16.6% vs 12.6%) and toxic effects of therapy/adverse events were higher in the RW (18.4% vs 9.4%). Further studies are needed to understand the clinical context that leads patients to discontinue treatment.