Immune blockade inhibition in breast cancer

Abstract

Besides limited success in treatment of melanoma and renal cell carcinoma, immune treatments of cancer (cancer immunotherapy) had not until recently met the great expectations associated with them over the years. This failure appears now to be reversed with the introduction of checkpoint (immune blockade) inhibitors. Two receptor-ligand checkpoint inhibition pairs, the one based on the inhibition of inhibitory receptor cytotoxic T lymphocyte-associated antigen 4 (CTLA-4) and the other based on the inhibition of the programmed death-ligand 1/programmed cell death-1 (PD-L1/PD-1) pair have entered the clinical arena. Melanoma leads the way followed by non-small cell lung cancer (NSCLC) in both of which such drugs are already approved for clinical use. Several other cancer types will follow as trials data accumulate. Breast cancer clinical data are mixed so far and the arising picture is one of efficacy dependent on sub-types and sub-sets. This article will review available data on checkpoint molecules expression in breast cancer cells that may be one determinant factor of effective inhibition, as well as other possible biomarkers of immune blockade inhibitors effectiveness in breast cancer. Emerging data of clinical trials of immune checkpoint inhibitors in breast cancer will also be presented. Development and validation of reliable predictive markers of response to this new category of anti-cancer drugs will help optimize results and spare patients not expected to respond the toxicity and cost of the drugs. Moreover, predictive markers may advance the understanding of resistance to these therapies in order to reverse it.