Recent Advances in Immune Checkpoint Inhibitors for Triple-Negative Breast Cancer

Chiara Corti,1– 4 Beyza Koca,1,2 Tasnim Rahman,1,2 Elizabeth A Mittendorf,1,2,5 Sara M Tolaney1,2,6 1Breast Oncology Program, Dana-Farber Brigham Cancer Center, Boston, MA, USA; 2Harvard Medical School, Boston, MA, USA; 3Division of New Drugs and Early Drug Development for Innovative Therapies, European Institute of Oncology IRCCS, Milan, Italy; 4Department of Oncology and Hematology-Oncology (DIPO), University of Milan, Milan, Italy; 5Division of Breast Surgery, Brigham and Women’s Hospital, Boston, MA, USA; 6Department of Medical Oncology, Dana-Farber Cancer Institute, Boston, MA, USACorrespondence: Sara M Tolaney, Dana-Farber Cancer Institute, 450 Brookline Ave, Boston, MA, 02215, USA, Tel +1 617-632-3800, Fax +1 617-632-1930, Email [email protected]: While immunotherapy has transformed treatment across various cancers, its impact on breast cancer is relatively limited. Recent advances have established immunotherapy as an effective approach for triple-negative breast cancer (TNBC), an aggressive subtype with limited therapeutic targets and poor prognosis. Specifically, pembrolizumab, an immune checkpoint inhibitor (ICI), is now approved for both first-line metastatic and early-stage TNBC. In metastatic TNBC, combining ICIs with chemotherapy, particularly pembrolizumab, has demonstrated survival benefits in patients with PD-L1–positive disease. However, extending these benefits to broader populations has proven challenging, highlighting the need for better patient selection and novel strategies. Emerging approaches include combining ICIs with antibody-drug conjugates, PARP inhibitors, dual ICIs, and bispecific antibodies targeting angiogenesis and immune checkpoints. These strategies aim to overcome resistance and expand immunotherapy’s efficacy beyond the PD-1/PD-L1 pathway. In early-stage disease, pembrolizumab combined with chemotherapy in the neoadjuvant setting has significantly improved pathologic complete response, event-free survival, and overall survival, establishing a new standard of care. Ongoing research aims to determine the optimal timing for ICI administration, explore less toxic chemotherapy backbones, utilize biomarkers for personalized treatment, and assess whether adding complementary treatments, such as radiation therapy for high-risk cases, can improve outcomes. This review examines the successes and setbacks of ICI use in TNBC, offering a comprehensive overview of current practices and future directions. It emphasizes optimizing ICI timing, leveraging biomarkers, and integrating novel agents to refine treatment approaches for both metastatic and early-stage TNBC. As immunotherapy continues to evolve, future research must address the unmet needs of this challenging breast cancer subtype, offering hope for improved outcomes.Keywords: immunotherapy, precision medicine, biomarker, drug development, breast cancer