Abstract GS3-08: Multiplatform analysis of matched primary and metastatic breast tumors from the AURORA US Network

摘要: Background: It has become increasingly clear that effective treatment of metastatic breast cancer (MBC) requires an in-depth understanding the molecular differences between primary tumors and metastases. The AURORA US Network was established to collect cancer-metastasis pairs for multi-platform genomic profiling in order identify drivers disease. both a retrospective prospective phase. This is first report Methods: Archived tissue samples from tumor at least one distant metastasis were retrospectively collected 83 MBC patients. Following internal quality assessment, 55 pts, including 105 distinct lesions, subject DNA low pass whole genome exome sequencing, methylation arrays, RNA sequencing. Early analyses these data include: methylation, gene expression microenvironmental signatures, somatic germline variants, copy number changes, structural variants primaries matched Results: Median age diagnosis 49 years (25-76); 32 (58%) Stage I or II presentation, 27 (49%) had family history cancer, 20 (36%) second primary. disease-free interval before developing 2 (range 0-36, 5 patients presented with IV). overall survival initial presentation 4 0-37). after 1 year 0-13), median three treatments. Primary banked 1977-2017 metastases 1999-2017. Clinical phenotypes included HR+ (49%), 15 triple negative (TNBC, 27%), 11 HER2+ (20%, 12 missing HER2 status). Intrinsic subtype distribution 17 Basal-like (31%), Luminal A 7 Normal-like (13%), HER2-enriched (9%), B, 8 pending. All cases remained Basal-like, while luminal tended gain HER2-Enriched features (5/18, p = 0.01). Overall, we identified significant metastasis-enriched alterations metabolism pathways, increase proliferation, loss differentiation signatures immune infiltrates progression; latter being most pronounced brain frequent mutations this cohort TP53, NCOR1, RUNX1. Interestingly, ERBB2, EGFR, ATM also mutated ≥10% sequenced. In almost all cases, CpG island hypermethylation clonally present persisted stably majority lesions. Promoter some lesions JAM3, important cellular adhesion molecule,and accompanied by reduced mRNA expression. CONCLUSIONS: Collection young high frequency primaries. Molecular characterization highlighted acquisition aggressive traits increased proliferation contrast, basal-like relatively unchanged, except activation. Ongoing be include clonal heterogeneity phylogeny, novel signature discovery, fusion, endogenous retrovirus detection. Citation Format: Tari King, Minetta C Liu, Marni B McClure, Toshinori Hinoue, Benjamin J Kelly, Chad Creighton, Jay Bowen, Kristen Leraas, Robyn T Burns, Sara Coppens, Salma Rezk, Amy L Garrett, Justin M Balko, Joel S Parker, Ben H Park, Ian Krop, Carey Anders, Katherine Hoadley, Julie Gastier-Foster, Mothaffar F Rimawi, Rita Nanda, Nancy U Lin, Claudine Isaacs, P. Kelly Marcom, Anna Maria Storniolo, Fergus Couch, Elaine R Mardis, Adrian V Lee, Uma Chandran, Peter W Laird, Susan G Hilsenbeck, Larry Norton, Andrea Richardson, W. Fraser Symmans, Lisa Carey, Antonio Wolff, E Davidson, Charles Perou, Network. Multiplatform analysis [abstract]. In: Proceedings 2019 San Breast Cancer Symposium; Dec 10-14; Antonio, TX. Philadelphia (PA): AACR; Res 2020;80(4 Suppl):Abstract nr GS3-08.