To further explore whether breast cancer tissues (BCT) participate in DOXIC aggravating effects by secreting sEVs into circulation, an orthotopic breast cancer mouse model was constructed and lentiviral shRNA targeting Rab27a, which has been proved to effectively inhibit sEVs secretion in BCCs, was intratumorally injected (Supplementary Fig. 3A). The gene discussed is RAB27A; the disease is breast carcinoma.