In the current studies, we demonstrate that topotecan (TPT), a topoisomerase I-targeting drug with a well-defined mechanism of action, stimulates major histocompatibility complex class I (MHC I) expression in breast cancer cells through elevated expression/secretion of interferon-β (IFN-β) and activation of type I IFN signaling. Here, IFNB1 is linked to breast carcinoma.