Current and emerging biologic therapies for triple negative breast cancer

Triple negative breast cancer, defined by a lack of estrogen receptor, progesterone receptor, or human epidermal growth factor2, accounts for approximately 15% of breast cancer patients. Treatment options have historically been limited to chemotherapy, which has significant toxicity and a suboptimal impact on the five-year relapse rate and survival.

Transcriptomic analyses reveal that TNBC is biologically heterogenous. Predictive biomarkers based on the distinct biology of the different subtypes of TNBC should identify patients that will derive the greatest benefit from a specifically targeted therapeutic agent. Two biomarker-driven treatments have recently been approved: poly-ADP ribose polymerase inhibitors for patients with germline BRCA mutations and atezolizumab in combination with nab-paclitaxel for patients expressing PD-L1 on tumor-infiltrating immune cells.

Identifying informative predictive biomarkers is critical for the optimal development of targeted drugs for TNBC. Some targeted agents, such as the antibody-drug conjugate sacituzumab govitecan-hziy and the precision medicines capivasertib and ipatisertib, have already shown promising results in early clinical trials, and the results of definitive phase 3 trials are eagerly awaited. Additionally, testing novel immunotherapies and other targeted agents in earlier stages of disease, particularly the neoadjuvant setting, is a high priority.