Novel Approaches to Immunotherapy in Triple Negative Breast Cancer

Context: Triple negative breast cancers (TNBC) constitute about 15% of breast neoplasms. In contrast to estrogen receptor (ER) or human epidermal growth factor receptor (HER2) positive breast cancers, which respond to hormonal therapy (such as tamoxifen) or anti-HER2 therapy (such as trastuzumab), respectively, the main standard therapy in either early or late stage TNBC is chemotherapy. Therefore, it is necessary to find new treatment modalities for TNBC patients. We searched the literature to find published studies on immunotherapy in triple negative breast cancer and the putative biomarkers of response to these treatments. Evidence Acquisition: We searched PubMed, Scopus, and Web of Science Core Collection with these keywords: "Triple negative breast cancer, Immunotherapy, Resistance, Response, Programmed cell death 1 receptor, CTLA-4, Tumor mutation burden, and Immune signature". Results: TNBC is considered a heterogeneous neoplasm with regard to molecular aberrations. Analysis of genomic expression profile of TNBC has delineated 4 subtypes. TNBC tumors show high genetic instability. Tumor infiltrating lymphocytes (TILs) are detected more in TNBCs, compared to other breast cancer types. It has been shown that the amount of CD8 positive T cells in TNBCs is an independent predictor of overall survival. Up to now, two immunotherapy strategies have been used in clinical trials of TNBC, including immune checkpoint blockers and therapeutic cancer vaccines. Tumor programmed cell death ligand 1 (PDL1) expression is the most widely used immunotherapy biomarker. Tumor mutation burden (TMB) can be a promising biomarker of response to immunotherapy. The more somatic mutations a cancer cell has, the more neoantigens it probably produces. Analysis of TMB can give an estimate of tumor mutation load. Increased somatic mutation load has also been observed in tumors with impaired mismatch repair (MMR). Conclusions: As TNBC is regarded a heterogeneous disease, the discovery of biomarkers of response to immunotherapy will increase the likelihood of response to these therapies. Further in-depth investigations are needed to find novel biomarkers of response to these immunotherapies for the better management of patients with TNBC.