Modern Immunotherapy in the Treatment of Triple-Negative Breast Cancer.

Abstract

Simple SummaryThis review summarizes reports from the latest clinical trials assessing the safety and clinical effectiveness of new biological drugs stimulating the immune system to fight cancer. The aim of this study is to show the enormous therapeutic potential of monoclonal antibodies in the treatment of cancer, in particular triple negative breast cancer (TNBC). Introduction of these innovative drugs to the standard clinical cancer therapies, including TNBC, allows for an increase in the response rate to the applied treatment, and consequently extending the lives of patients suffering from cancer. We hope to draw attention to the extremely difficult-to-treat TNBC, as well as the importance of the development of clinical trials evaluating drugs modulating the immune system in TNBC therapy.Triple-Negative Breast Cancer is a subtype of breast cancer characterized by the lack of expression of estrogen receptors, progesterone receptors, as well as human epidermal growth factor receptor 2. This cancer accounts for 15–20% of all breast cancers and is especially common in patients under 40 years of age, as well as with the occurring BRCA1 mutation. Its poor prognosis is reflected in the statistical life expectancy of 8–15 months after diagnosis of metastatic TNBC. So far, the lack of targeted therapy has narrowed therapeutic possibilities to classic chemotherapy. The idea behind the use of humanized monoclonal antibodies, as inhibitors of immunosuppressive checkpoints used by the tumor to escape from immune system control, is to reduce immunotolerance and direct an intensified anti-tumor immune response. An abundance of recent studies has provided numerous pieces of evidence about the safety and clinical benefits of immunotherapy using humanized monoclonal antibodies in the fight against many types of cancer, including TNBC. In particular, phase three clinical trials, such as the IMpassion 130, the KEYNOTE-355 and the KEYNOTE-522 resulted in the approval of immunotherapeutic agents, such as atezolizumab and pembrolizumab by the US Food and Drug Administration in TNBC therapy. This review aims to present the huge potential of immunotherapy using monoclonal antibodies directed against immunosuppressive checkpoints—such as atezolizumab, avelumab, durvalumab, pembrolizumab, nivolumab, cemiplimab, tremelimumab, ipilimumab—in the fight against difficult to treat TNBCs as monotherapy as well as in more advanced combination strategies.