Polychlorinated Biphenyls and Breast Cancer: Evidence, Mechanisms, and Risk Management

Shuaiyang ZhangHongliang CaoYing LiuRunzhou LianXinxin GuiYuting ZhuTianzi KongAiping Shi^*

• First Affiliated Hospital of Jilin University, Changchun, China

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 AhR and ER triggers mitochondrial dysfunction and inhibits TET enzyme activity, creating an oxidative state that establishes the epigenetic locking of tumor suppressor genes. We delineate subtype-specific trajectories, identifying how dioxin-like congeners drive AhR-mediated stemness in triple-negative phenotypes, while non-dioxin-like mixtures contribute to malignant evolution through chronic, selective oxidative pressures. 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.