Neoadjuvant treatments in triple-negative breast cancer patients: where we are now and where we are going

Abstract

Triple-negative breast cancer (TNBC) remains the poorest-prognosis breast cancer (BC) subtype. Gene expression profiling has identified at least six different triple-negative subtypes with different biology and sensitivity to therapies. The heterogeneous nature of TN tumors may justify the difficulty in treating this BC subtype. Several targeted agents have been investigated in clinical trials without demonstrating a clear survival benefit. Therefore, systemic chemotherapy remains the cornerstone of current clinical practice. Improving the knowledge of tumor biology is mandatory for patient management. In stages II and III, neoadjuvant systemic treatment is an effective option of care. The achievement of a pathological complete response represents an optimal surrogate for survival outcome as well as a test for tumor drug sensitivity. In this review, we provide a brief description of the main predictive biomarkers for tumor response to systemic treatment. Moreover, we review the treatment strategies investigated for TNBCs in neoadjuvant settings focusing on experimental drugs such as immunotherapy and poly [ADP-ribose] polymerase inhibitors that hold promise in the treatment of this aggressive disease. Therefore, the management of TNBC represents an urgent, current, unmet need in daily clinical practice. A key recommendation is to design biology-driven clinical trials wherein TNBC patients may be treated on the basis of tumor molecular profile.

Keywords: BRCA; PARP-1 inhibitors; immunotherapy; neoadjuvant chemotherapy; platinum; triple-negative breast cancer.

Figure 1

Triple negative breast cancer (TNBC) molecular subtypes classified according to gene expression and the main involved pathways. Each of these subclasses show varying pathological complete response (pCR) rates following standard neoadjuvant chemotherapy. Promising therapies for every molecular subtype have been suggested.