NF-κB activation and cytokine dysregulation: a pathogenic loop in breast cancer inflammation - a narrative review

Chronic inflammation is a critical driver of breast cancer initiation and progression, with the nuclear factor kappa B (NF-κB) pathway acting as a central regulator of pro-inflammatory and oncogenic signaling. Dysregulated cytokine production reinforces NF-κB activation, establishing a self-perpetuating inflammatory loop that sustains tumor growth and immune evasion. This review explores the molecular interplay between NF-κB activation and cytokine dysregulation in breast cancer, emphasizing their combined role in shaping the tumor microenvironment and promoting malignancy. Persistent NF-κB activation - induced by cytokines such as interleukin-1β, interleukin-6, interleukin-8, and tumor necrosis factor-alpha - enhances transcription of genes governing proliferation, angiogenesis, and metastasis. In turn, these cytokines activate feedback loops that maintain NF-κB signaling, leading to chronic inflammation and therapy resistance. The NF-κB-cytokine axis also modulates immune checkpoint expression, supporting tumor immune escape. Understanding this dynamic interplay provides insight into novel therapeutic approaches, including NF-κB inhibitors, anti-cytokine antibodies, and combinatorial anti-inflammatory strategies. NF-κB activation and cytokine dysregulation form a pathogenic loop central to breast cancer inflammation, progression, and treatment resistance. Targeted disruption of this loop represents a promising avenue for precision-based therapeutic intervention and improved clinical outcomes.