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585 Background: The use of neoadjuvant chemotherapy (NAC) in patients with early-stage breast cancer (EBC) increases the opportunity for genomic testing which can help predict treatment response and optimize outcomes. MammaPrint (MP) classifies tumors as having a Low Risk (LR) or High Risk (HR) of distant recurrence. MP with BluePrint (BP), a molecular subtyping assay, categorize tumors as Luminal A (MP LR), Luminal B (MP HR), HER2, or Basal-Type. Our recent analysis comparing matched pre- and post-NAC tumors found 25% of pre-NAC Luminal B tumors changed to Luminal A post-NAC, which corresponded with improved 5-year outcomes compared with patients who remained Luminal B. Here, we report differential gene expression (DGE) and pathway analyses in these matched tumors that may distinguish the different responses. Methods: Among the patients with EBC who received NAC at Cedars Sinai Medical Center between 2007-2016, 38 with residual disease (RD) had paired pre- and post-NAC tissues. In patients with Luminal tumors, 8 were Luminal B pre- and post-NAC (HR/HR), and 7 were Luminal B pre-NAC but changed to Luminal A post-NAC (HR/LR). Limma R package was used for quantile normalization and DGE analyses. Differentially expressed genes (DEG) with < 0.05 false discovery rate and > 2-fold change were considered significant. Functional pathway enrichment was performed using Metascape. Results: Within HR/LR tumors, a DGE analysis identified 104 DEGs in post-NAC tissues relative to pre-NAC, with changes in cell cycle/proliferation pathways. Interestingly, there was a more robust transcriptional change in HR/HR tumors, with 956 DEGs between post- and pre-NAC samples, with enrichment of extracellular matrix organization, angiogenesis, and wound healing pathways. Notably, immune pathway enrichment was in both HR/LR and HR/HR groups, although the nature of enrichment differed. Immune deconvolution identified significant increases in activated myeloid dendritic cells (DC) and CD8+ T cells in HR/LR but not in HR/HR post-NAC tumors, suggestive of a host immune response. Conclusions: Although post-NAC RD correlates with poor prognosis, even in Luminal tumors, these data suggest gene expression profiling may distinguish a subset with good prognosis. Using matched samples, we assessed the transcriptional differences in tumors that changed MP risk (HR/LR) with tumors that stayed MP HR post-NAC (HR/HR). Overall, HR/HR tumors had a larger transcriptional response with metastatic-related pathway enrichment. Given these patients with HR/HR tumors displayed worse outcomes, pathway changes may indicate resistance and patients may need additional therapy. Differential changes in immune cells between HR/HR and HR/LR tumors were also observed. The activated immune response in HR/LR tumors may be a biomarker for therapy response and improved outcome and will be the focus of further evaluation.

565 Background: Sentinel lymph node (SLN) biopsy guides breast cancer treatment and prognostication. To date, there have been few studies examining the genetics of SLN metastasis in triple negative breast cancer (TNBC). The aim of this study is to characterize and compare gene expression patterns of primary breast cancers and autologous matched SLN metastases. Methods: Patients with stage 2-3 ER/PR negative, HER2 negative TNBC with macrometastasis to the SLN who did not have neoadjuvant therapy were selected. The tumor-specific area was isolated from breast and SLN paraffin embedded tissue sections. Gene expression of a panel of 2567 cancer-associated genes was analyzed with the HTG EdgeSeq system coupled with the Illumina Next Generation Sequencing (NGS) platform. Results were validated with RNA-scope assays for RNA in situ detection. Results: 18 pairs of TNBC and matched SLN metastasis were analyzed for 2567 genes. Compared with the primary TNBC, SLN metastasis had 34 statistically significant upregulated genes and 31 downregulated genes. SLN metastasis had at least a 5-fold change (FC) in upregulation in 3 genes and downregulation in 3 genes, compared to primary TNBC [Table]. Notably, there was an upregulation of anti-apoptosis and survival signaling genes (i.e. BIRC3) in the SLN metastasis. There was also an upregulation of chemotaxis genes (CCL13, CXCL19, CXCL21, CXCR5, TNFSF11, p