Targeted Therapies for Triple-Negative Breast Cancer: Combating a Stubborn Disease

Triple-negative breast cancers (TNBCs) constitute a heterogeneous subtype of breast cancers that have a poor clinical outcome. Although no approved targeted therapy is available for TNBCs, molecular-profiling efforts have revealed promising molecular targets, with several candidate compounds having now entered clinical trials for TNBC patients. However, initial results remain modest, thereby highlighting challenges potentially involving intra- and intertumoral heterogeneity and acquisition of therapy resistance. We present a comprehensive review on emerging targeted therapies for treating TNBCs, including the promising approach of immunotherapy and the prognostic value of tumor-infiltrating lymphocytes. We discuss the impact of pathway rewiring in the acquisition of drug resistance, and the prospect of employing combination therapy strategies to overcome challenges towards identifying clinically-viable targeted treatment options for TNBC.

TrendsTriple-negative breast cancers (TNBCs) account for ∼15–20% of all diagnosed breast cancer cases.TNBCs are themselves heterogeneous, composed of at least 4–6 definable molecular subtypes.Proliferative and survival-dependent pathways represent targets in TNBC.Other promising therapeutic targets in TNBC include those that control the cell cycle and the DNA damage responses.Acquisition of resistance to targeted therapies is a hurdle to overcome for effective TNBC therapy.