Combination immunotherapy strategies for triple-negative breast cancer: current progress and barriers within the pharmacological landscape

Triple-negative breast cancer (TNBC) is a breast cancer subtype characterized by poorer prognosis. Despite that TNBC can display immunogenic features, anti-PD(L)1 monotherapy strategies have resulted in disappointing results, underscoring the need to optimize their use in TNBC. Among many, combining immunotherapy with other agents to exploit the synergistic effect of different drugs has been explored. Such a combination approach led to the approval of immune checkpoint inhibitors (ICIs) plus chemotherapy in both metastatic and early setting. Nevertheless, primary or secondary resistance to ICIs remains a major hurdle to overcome, with a major need to explore novel combination strategies.This review summarizes the biological rationale, current evidence, and ongoing clinical trials of immunotherapy combined with novel immunotherapeutics, chemotherapy, targeted compounds, and antibody-drug conjugates.The treatment landscape of TNBC is in continuous changes. ICIs are now part of the clinical practice; however, several unmet needs still remain, including the need to overcome resistance and prolong benefit of ICIs. Exploiting synergism between different agent has emerged as an attractive strategy to extend the benefit obtained with ICIs. The goal of future research will be to unveil the mechanisms underlying resistance to ICIs and to identify better biomarkers for patient selection.