Polychlorinated biphenyls and breast cancer: evidence, mechanisms, and risk management

Epidemiological inconsistencies currently obscure the causal link between polychlorinated biphenyls (PCBs) and breast cancer. This review synthesizes multi-disciplinary evidence to characterize PCBs not as passive exposure correlates but as active drivers of tumorigenesis via a metabolic–oxidative–epigenetic axis. We examine how lipophilic congeners accumulate in adipose reservoirs, extending toxicity across the life course beyond distinct susceptibility windows. Mechanistically, receptor crosstalk between the aryl hydrocarbon receptor (AhR) and the estrogen receptor (ER) triggers mitochondrial dysfunction and inhibits ten–eleven translocation (TET) enzyme activity, creating an oxidative state that establishes epigenetic locking of tumor suppressor genes. We propose subtype-specific evolutionary trajectories: postulating that dioxin-like congeners drive AhR-mediated stemness in triple-negative phenotypes, whereas non-dioxin-like mixtures impose an oxidative bottleneck that facilitates the acquisition of therapeutic resistance. Finally, we propose an integrated risk management framework connecting upstream environmental remediation (e.g., bio-nano systems) with downstream clinical stratification and gut–liver axis interventions. This framework establishes a biological foundation for understanding PCB-induced malignancy while defining actionable pathways for exposure-informed precision prevention.