TUMOR ANGIOGENESIS IN TRIPLE-NEGATIVE BREAST CANCER: A COMPREHENSIVE ANALYSIS

Abstract

Triple-negative breast cancer (TNBC), a clinically aggressive and therapeutically challenging subtype, is characterized by the absence of estrogen receptor, progesterone receptor, and HER2 expression. This study presents a comprehensive secondary analysis of tumor angiogenesis as a central driver of TNBC progression. Drawing on recent preclinical and clinical evidence, we explored the molecular, cellular, and microenvironmental mechanisms that contribute to pathological neovascularization in TNBC. The findings reveal a pronounced upregulation of vascular endothelial growth factor A (VEGF-A), with a 4.5-fold increase in expression, positioning it as the dominant pro-angiogenic factor in TNBC. Additional mediators such as FGF-2, PDGF-BB, Angiopoietin-1, and Ephrin-A1 also demonstrated significant elevation, supporting a multifactorial angiogenic landscape. The VEGF-VEGFR signalling pathway plays the most influential role. Nonetheless, angiogenesis is facilitated by displacement of the VEGF-VEGFR pathway by the angiopoietin-Tie2 and ephrin-Eph systems.  Angiogenic signalling in the tumour microenvironment is greatly amplified through activities of hypoxic regions, cancer-associated fibroblasts and immune cells.  Anti-angiogenic drugs such as bevacizumab and sorafenib have had limited success in clinical practice due to the complex and multifaceted ways by which angiogenic signalling is regulated in TNBC.  Several illustrations and tables provide visual evidence of VEGF’s dominant role, the complexity of signalling networks and treatment approaches’ limited effectiveness.  These findings suggest that angiogenesis in TNBC is governed by a complex and interchangeable pathway, calling for combination therapies to be most effective.  Combining angiogenesis inhibition with immunomodulatory and targeted treatments may lead to improved responses in patients with TNBC.