Oxidative stress and inflammation in breast cancer: Mechanistic interactions and clinical implications

Table 1 Major sources of reactive oxygen species in breast cancer and their cellular consequences

Source of ROS	Main mechanism	Key downstream effects	Representative pathways/markers
NADPH oxidases (NOX family)	Activation by oncogenic and inflammatory signals in tumor and stromal cells	Increased superoxide production, lipid and protein oxidation, promotion of proliferation and migration	NF-κB, MAPK, PI3K/AKT, MDA, protein carbonyls
Mitochondrial electron transport chain	Electron leakage under hypoxia and high metabolic demand	Mitochondrial ROS accumulation, mtDNA damage, genomic instability, induction of EMT	HIF-1α, DAMPs, 8-OHdG
Oncogene-driven metabolic reprogramming	Warburg effect, enhanced glycolysis, and altered TCA cycle	Elevated basal ROS, redox-sensitive signaling, adaptation of cancer stem cells, therapy resistance	PI3K/AKT, HER2, Nrf2-regulated antioxidant genes
Chronic inflammation	Activation of immune cells (macrophages, neutrophils) and cytokine signaling	Sustained ROS and RNS generation, macromolecular damage, self-perpetuating inflammatory loop	TNF-α, IL-6, COX-2, CXCL8/IL-8
Environmental and lifestyle factors	Smoking, radiation, pollutants, dietary factors	Direct oxidative damage to DNA, lipids and proteins, initiation and promotion of carcinogenesis	8-OHdG, MDA, nitrotyrosine, myeloperoxidase
Anticancer therapies (radio/chemotherapy)	ROS generation as part of cytotoxic mechanism	Tumor cell killing at high ROS, but also selection of resistant clones and long-term tissue/vascular damage	Doxorubicin-induced ROS, radiotherapy-induced oxidative biomarkers

8-OHdG: 8-Hydroxy-2′-deoxyguanosine; ROS: Reactive oxygen species; DAMP: Damage-associated molecular pattern; Nrf2: Nuclear factor erythroid 2-releated factor 2; TNF-α: Tumor necrosis factor-α; IL: Interleukin; TCA: Tricarboxylic acid cycle; RNS: Reactive nitrogen species; MDA: Malondialdehyde; EMT: Epithelial-mesenchymal transition.