47P Immune tumor microenvironment and markers of apoptosis in breast cancer in carriers of hereditary mutations in the BRCA1 gene

Abstract

Tumor immune microenvironment is currently recognized as an important participant in carcinogenesis, influencing the behavior of tumor cells and treatment efficacy. It is suggested that defects in BRCA1/2 genes contribute to a high mutation load and high immunogenicity, which modulates immune microenvironment. At the same time, it was shown that BRCA1/2-associated breast cancer tumors do not belong to the category of immunoactive ones. In addition, there is evidence of the additional evaluation of TP53 mutation in these tumors and disruption of the cell death process, which can also be a factor of resistance to therapy. 40 patients with breast cancer with BRCA1 mutations 185delAG, 4153delA, 5382insC, 3819DELGTAA, 3875delGTCT, 300T>G, 2080delA and BRCA2 (6174delT)) determined by real-time polymerase chain reaction (PCR) were included. Immunohistochemical study was performed using monoclonal antibodies to Ki67, p53, CD8, CD4, CD68, CD163, BCL2. In the presented study patients with BRCA1-associated breast cancer, had high low tumor CD4/CD8 ratio in 50% of cases, which characterizes an immunosuppressive microenvironment. Mutation BRCA1 5382insC is associated with high level of CD4+ T-lymphocytes (p˂0.05), G3 is associated with a low CD4/CD8 ratio (p=0.056) and a low levels of CD68+M1, CD163+M2-macrophages (p=0,022, p=0.002); T1 correlates with high levels of CD8+ TILs (p=0.038) and high levels of CD163 (p=0.033). High Ki-67 is associated with a lack of BCL2 expression (p=0.04). Negative expression of BCL2 occurred in 52.5% of cases. A high level of p53 expression is described as the main type of expression in these tumors, suggesting a combination of TB53 and BRCA1 mutations and a violation of the mechanism of cell death in these patients. The immunosuppressive type of microenvironment prevails in the tumors of breast cancer patients with hereditary mutations in the BRCA1 gene, where a violation of the mechanism of cell death in BRCA1-deficient breast cancer was revealed. The main directions of future therapy of these tumors may be modification of the immune microenvironment and activation of the mechanisms of cell death.