Abstract
Triple-negative breast cancer (TNBC) is traditionally treated with systemic chemotherapy, often resulting in significant off-target toxicity. In this study, we assess the efficacy of intraductal chemotherapeutic delivery, aimed at reducing systemic side effects. Using an in situ TNBC model, created by intraductal injection of 4T1-luc cells, we identified day 3 post-tumor implantation as an optimal early intervention point. Echocardiographic analysis confirmed that intraductal administration of eribulin (ERI) or doxorubicin (DOX) did not cause cardiac dysfunction or apoptosis. Our results demonstrate that intraductal delivery of ERI and DOX significantly enhances anti-tumor and anti-metastatic effects. Mechanistically, ERI followed by DOX increased intratumoral perfusion, improved drug concentration, reversed epithelial-mesenchymal transition, and inhibited tumor cell invasion and metastasis. Additionally, this approach triggered immunogenic cell death and activated a systemic anti-tumor immune response. These findings underscore the potential of intraductal chemotherapy as a safe, highly effective approach, offering a preclinical foundation for minimally invasive TNBC therapies.