Updated Neoadjuvant Treatment Landscape for Early Triple Negative Breast Cancer: Immunotherapy, Potential Predictive Biomarkers, and Novel Agents

SIMPLE SUMMARY: In recent years, several agents have been tested in randomized clinical trials in addition to anthracycline and taxane-based neoadjuvant chemotherapy (NACT) in early-stage triple-negative breast cancer (TNBC) to improve pathological complete response rate and, ultimately, survival outcome. Platinum agents, immune checkpoint inhibitors (ICIs), and PARP-inhibitors are the most extensively studied, while established predictors of their efficacy are lacking. Based on the biological features of TNBC, the purpose of this review is to provide an overview of the role of platinum agents, immunotherapy, and novel target therapies in the neoadjuvant setting. Moreover, based on safety issues and financial costs, we provide an overview of potential biomarkers associated with increased likelihood of benefit from the addition of platinum, ICIs, and novel target therapies to NACT. ABSTRACT: Triple-negative breast cancer (TNBC) is characterized by the absence of hormone receptor and HER2 expression, and therefore a lack of therapeutic targets. Anthracyclines and taxane-based neoadjuvant chemotherapy have historically been the cornerstone of treatment of early TNBC. However, genomic and transcriptomic analyses have suggested that TNBCs include various subtypes, characterized by peculiar genomic drivers and potential therapeutic targets. Therefore, several efforts have been made to expand the therapeutic landscape of early TNBC, leading to the introduction of platinum and immunomodulatory agents into the neoadjuvant setting. This review provides a comprehensive overview of the currently available evidence regarding platinum agents and immune-checkpoint-inhibitors for the neoadjuvant treatment of TNBC, as well as the novel target therapies that are currently being evaluated in this setting. Taking into account the economic issues and the side effects of the expanding therapeutic options, we focus on the potential efficacy biomarkers of the emerging therapies, in order to select the best therapeutic strategy for each specific patient.