Clinicopathological importance of microenvironment in triple negative breast cancers

Aim: Breast cancer is the most common cancer type among women and the leading cause of cancer death. İn its treatment, addition to surgical treatment, hormonal therapy (against estrogen and progesterone receptors) and targeted agents according to "Human epidermal growth factor receptor 2" (HER2) are used. However, treatment options for triple negative breast carcinomas are limited. This group known to be has worse prognosis than other groups and studies to developt treatment moptions for this group is gaining importance. Most of these studies are aimed at investigating the tumor microenvironment and the immune response against the tumor. Agents used against the increase in PD-L1 receptor expression, which is one of the defense mechanisms of the tumor, are promising due to their effects on survival. Agents used against the PD-L1 receptor expression on tumor cells, which is one of the defense mechanisms of the tumor, are promising due to their effects on survival. There are many studies showing that lymphocytes (Treg and CD8+ T lymphocytes) and macrophages (M1 and M2 macrophages) in the tumor microenvironment are effective on prognosis. In our study, the density and localization of immune cells forming the tumor microenvironment and the expression status of PD-L1 were compared with conventional prognostic parameters and with each other; It is aimed to investigate the effect of immunity on clinicopathological factors and to shed light on the appropriate patient selection in immunotherapy. Material and Methods: Materials of 52 patients who were diagnosed with triple negative breast carcinoma and did not receive systemic treatment between January 2017 and December 2021 in Çukurova University Balcalı Hospital Pathology Department were included in the study. CD8, FOXP3, CD163 and PD-L1 were applied for all cases by immunohistochemically. CD8,FOXP3 and CD163 expressions were separately evaluated in intratumoral and stromal areas. PD-L1 expression was also evaluated separately in immune cells and tumor cells. Findings: The mean age of our cases at the time of diagnosis was 48, and the mean follow-up period was 33 months. In our study, high TIL levels were seen in 30% of the cases and were associated with high PD-L1 positivity. There was no significant difference between TIL levels and conventional prognostic parameters. PD-L1 positivity was found to be statistically significantly higher in cases without LVI, but no significant correlation was found with tumor size, lymph node metastasis, survival and mortality. PD-L1 expression in immune cells was positively correlated with intratumoral and stromal FOXP3 and CD8 and intratumoral CD163 expression. Intratumoral and stromal CD8(+) levels between surviving and deceased cases were statistically significantly different and had a higher median value in surviving cases. In the microenvironment; When CD8 expression increased, stromal FOXP3 expression also increased significantly, again FOXP3 expression was positively correlated with stromal and intratumoral CD163 expression. Conclusion: Tumor microenvironment has gained importance in guiding the treatment of triple negative breast cancers. We think that the composition, density and localization of immune cells and checkpoint molecules such as PD-L1 are important prognostic parameters in triple negative breast carcinomas. Our results support that investigation of TILs in triple negative breast carcinomas will provide useful prognostic and therapeutic information. However, we believe that further studies in larger case series are necessary to evaluate immune cell marker expression and treatment outcomes. Keywords: triple negative breast cancer, tumor microenvironment, programmed cell death ligand 1 tumor infiltrating lymphocytes, CD8, FOXP3, CD163, M2 macrophages, regulatory T lymphocytes, cytotoxic T lymphocytes.