Recent Advances in Antibody-Drug Conjugates and Immunotherapy Combinations for Treatment of Triple-Negative Breast Cancer

Huihui Chen,1– 3,* Wei Lu,2– 4,* Yunxiang Zhou,1– 3,* Xianan Guo,1– 3 Shijie Wu,1– 3 Yiding Chen1– 3 1Department of Breast Surgery and Oncology (Key Laboratory of Cancer Prevention and Intervention, China National Ministry of Education, Key Laboratory of Molecular Biology in Medical Sciences), The Second Affiliated Hospital, Zhejiang University School of Medicine, Hangzhou, Zhejiang, People’s Republic of China; 2Zhejiang Provincial Clinical Research Center for Cancer, The Second Affiliated Hospital, Zhejiang University School of Medicine, Hangzhou, Zhejiang, People’s Republic of China; 3Cancer Center, Zhejiang University, Hangzhou, Zhejiang, People’s Republic of China; 4Department of Colorectal Surgery and Oncology (Key Laboratory of Cancer Prevention and Intervention, China National Ministry of Education, Key Laboratory of Molecular Biology in Medical Sciences), The Second Affiliated Hospital, Zhejiang University School of Medicine, Hangzhou, Zhejiang, People’s Republic of China*These authors contributed equally to this workCorrespondence: Yiding Chen, Email ydchen@zju.edu.cn Wei Lu, Email 3120101767@zju.edu.cnAbstract: Triple-negative breast cancer (TNBC) remains a therapeutic challenge due to its aggressive nature and lack of ER, PR and HER2 expression. Recent advances, however, are reshaping its treatment landscape, particularly with antibody-drug conjugates (ADCs) and immunotherapies. ADCs such as sacituzumab govitecan and datopotamab deruxtecan have demonstrated superior efficacy over standard chemotherapy in metastatic TNBC. Furthermore, combining these ADCs with immune checkpoint inhibitors is emerging as a powerful strategy to enhance antitumor activity, as evidenced by encouraging results from trials like MORPHEUS-panBC and BEGONIA. While most evidence currently centers on metastatic disease, these novel combinations are also being rapidly evaluated in neoadjuvant and adjuvant settings. Given this rapid progress, this article aims to summarize recent advances in ADCs and immunotherapy combinations for TNBC, discuss their synergistic mechanisms, and provide insights for future personalized therapeutic strategies.Keywords: triple-negative breast cancer, antibody-drug conjugates, immunotherapy