Characterization of the immune microenvironment in matched primary and metastatic breast cancer lesions from the AURORA study: BIG 14-01.

1009 Background: Immunotherapy benefit in patients with metastatic breast cancer (MBC) is limited to patients with triple negative breast cancer and PD-L1 expression in the tumor sample. Multi-omics characterization of the anti-cancer immune response in MBC could provide novel insights into the mechanisms behind immune response failure. Methods: The AURORA program (NCT02102165) enrolled patients with MBC who received at most one line of treatment in the metastatic setting. RNA sequencing was performed on primary and metastatic lesions. Stromal tumor infiltrating lymphocytes (sTIL) were scored in line with the International Immuno-Oncology Biomarker Working Group for Breast Cancer recommendations. T cell and B cell receptor (TCR and BCR) analysis was performed with MiXCR. Deconvolution of bulk RNA sequencing data was performed using xCell. ImmuneScore-normalized Relative Abundance metastasis/primary Ratios (RAR) of immune cell types were calculated. All comparisons between primary and metastatic lesions were performed on matched samples. Wilcoxon signed-rank tests were used. Results: As expected, sTILs decreased from primary to metastatic lesion. However, 9% of metastatic lesions still had ⪰20% sTILs. Matched RNA expression data was available for 204 patients. Relative abundance of macrophages (RAR 3.3, p<0.001) and Th1 cells (RAR 1.5, p<0.001) was increased in the metastases, while Treg cells (RAR 0.12, p<0.001), CD8+ T cells (RAR 0.32, p<0.001) and B cells (RAR 0.32, p<0.001) decreased the strongest. Metastases with ⪰20% sTILs had higher Treg cells (p<0.001) and B cells (p<0.001) compared to metastases with low sTILs, which had more Th1 cells (p<0.001), mast cells (p<0.001) and NKT cells (p<0.001). De novo metastatic and synchronous primary samples had more BCR (p<0.001) and TCR (p<0.001) clones in common as compared to non-de novo metastatic cancers. Conclusions: sTIL percentage decreased from primary tumor to metastatic lesion. Metastatic lesions with many sTILs (⪰20%) were enriched for immune response suppressing regulatory T cells. [Table: see text]