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

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.

Evolving treatment landscape of immunotherapy in breast cancer: current issues and future perspectives

“…The introduction of ICIs for the treatment of patients with early TNBC raises many interesting issues warranting new translational studies and clinical trials 59 , 89 , 90 ( Figure 1 ).…”

Conservative Surgery in cT4 Breast Cancer: Single-Center Experience in the Neoadjuvant Setting

“…The use of adjuvant therapy was confirmed in relation to the type of surgery, the tumor biology, and definitive pathological stadiation. In case of residual disease, patients with TN subtype received in most cases capecitabine [23][24][25], patients with HER2+ tumor were given Trastuzumab or Trastuzumab Emtansine (TDM-1) for up to 14 cycles, in relation to time of cancer diagnosis [26]. Patients with estrogen receptor/progesteron receptor (ER/PGR) expression ≥1% received endocrine therapy (Tamoxifen or Aromatase inhibitors with or without LHRH analogue, if in a pre-or postmenopausal status respectively) for a maximum of 7-10 years [27,28].…”

HER3 Alterations in Cancer and Potential Clinical Implications

“…These patients have a poorer prognosis with fewer treatment options. Although there have been recent advances in triple negative breast cancer including approved treatments targeting human trophoblast cell-surface antigen 2 (Trop-2), systemic therapies, and immunotherapy [ 50 , 51 , 52 ].…”