The integrated genomic and immune landscapes of lethal metastatic breast cancer (MBC).

1009Background: The heterogeneous fates of MBC preclude our understanding of both resistance to therapy and escape from cancer immunoediting. Here, we performed a comprehensive molecular analysis of lethal MBC patients (pts), interrogating both the malignant and immune tumor microenvironment (TME) compartments, and T-cell receptor (TCR) repertoires, across multiple metastases (mets). Methods: Multi-platform profiling of mets (N = 182 mets to 22 organs, 5-36 mets/pt), primary tumors (pr) (N = 6) and ctDNA from body fluids (4.7/pt) in 10 warm autopsies of MBC pts (5 ER+/HER2-, 3 ER+/HER2+, 1 ER-/HER2+, 1 ER-/HER2-), included exome seq (N = 86), shallow whole genome seq (N = 168), RNA seq (N = 61), ultra-deep targeted seq (TS) (N = 243), TCRseq (N = 70) and IHC (N = 102). State-of-the-art bioinformatics was applied to the data. Results: Mutation (mut) burden landscape varied between pts (11,579 mut, median 255.41 mut/pt) and across mets within each pt (median 122 mut/met); was greater than TCGA mut burden (m...