Neoadjuvant Therapy for Triple-Negative Breast Cancer: The Challenge of Translating Biological Concepts into Effective Treatments

With the help of ever more powerful research tools triple-negative breast cancer (TNBC) is slowly yielding its secrets. The neoadjuvant setting gives us the best opportunity to address questions raised by the biologic heterogeneity of the disease, and eventually design individualized treatment plans for patients who are identified as likely to have a suboptimal response to chemotherapy. However, given a plethora of aberrantly activated pathways, exacerbated by its genomic instability, the challenge is to separate what drives the behavior of TNBC from the consequences of that behavior. This article reviews our current understanding of TNBC, including recent efforts to identify clinically relevant subsets of the disease, the role of treatments that exploit defects in DNA repair, including chemotherapeutic agents such as the platinum analogues, and biologic agents such as the poly ADP-ribose polymerases (PARP) inhibitors, and then discusses potential targeted approaches to its treatment, most of which are still early in development.