Tumor Infiltrating Lymphocytes Associated with Brain Metastasis in Breast Cancer.

2059 Background: Breast cancer represents the second most common cause of brain metastasis (BM). Though tumor-infiltrating lymphocytes (TILs) and immunotherapies have been studied in primary breast cancer, little is known about TILs in BM from breast cancer. The aim of this study is to characterize the immune response to BM in breast cancer. Methods: The cohort included 75 initial and recurrent BM samples and 20 matched primary breast tumors. Stromal (sTILs) were evaluated on H&E sections and scored according to international TILs working group guidelines and categorized as having no, low (1-5%), moderate (6-20%) or high ( > 20%) TILs. Tumor DNA/RNA was extracted on corresponding archival FFPE material. Gene expression profiling was performed using Affymetrix Human Transcriptome Array 2.0 microarrays. PAM50 subtypes were assigned by clustering samples using median-subtracted PAM50 gene expression levels. Gene expression levels of programmed cell death 1 (PD1), programmed cell death ligand 1 (PD-L1), cytotoxic T-lymphocyte associated protein 4 (CTLA4), and forkhead box P3 (FOXP3) were compared in this cohort. Results: Of the 75 BM evaluated, 34 (45%) had no sTILs, 29 (39%) had low sTILs, 10 (13%) had moderate sTILS, and 1 (1%) had high sTILs. sTILs were significantly lower in the BM when compared with matched primary tumors (p = 0.0025). When comparing the level of BM sTILs in the PAM50 subtypes, the HER2-enriched subtype more commonly exhibited moderate to high sTILs compared luminal A, luminal B, and normal-like (p = 0.065). No association was seen between time to develop BM and % sTILs (p = 0.68). Though primary and BM were found to express both PD1 and FOXP3, only FOXP3 expression was found to be higher in primary tumors compared to BM (p = 0.0025). There was no association between PD1 and FOXP3 expression and PAM50 subtype or BM sTILS (p > 0.05). Significant PD-L1 and CTLA4 expression was not identified in primary tumors or BM. Conclusions: Overall, BM from breast cancer have relatively low sTILs expression. The expression of PD1 and FOXP3 in BM from breast cancer suggests that further investigation of the immune response in BM and clinical trials with immune checkpoint inhibitors should be considered for this poor prognosis population.