BM-28 * BIOLOGICAL PATHWAYS ASSOCIATED WITH BREAST CANCER METASTASIS TO THE BRAIN

Abstract

BACKGROUND: Brain metastases (BM) from breast cancer are associated with poor prognosis. While basal-like and HER2+ cancers are at highest risk of BM, no effective treatments exist. Comprehensive characterization of the transcriptome of matched primary breast (PB) tumors and BM may allow for discovery of pathways mediating BM. METHODS: Pathology records were searched for surgical resection of BM from PB. Archival FFPE material was obtained along with chart and tumor registry clinical data. TMA sections were stained with ER, PR and HER2. Tumor DNA/RNA was extracted from macrodissected 2 mm cores from FFPE. Gene expression profiling was performed using Affymetrix HTA 2.0 arrays on 96 FFPE samples for whom sufficient RNA was available. PAM50 subtypes were derived and differential gene expression between BM and PB was estimated using the Mann-Whitney-Wilcoxon test followed by multiple testing correction. Pathway enrichment analysis was performed using KEGG and NCI Pathway Interaction Databases. RESULTS: 68 BM were identified. 30 had matching PB tissue. BMs were predominantly parenchymal (dural-based, 11). Most were supratentorial. We found a total of 390 genes to be significantly differentially expressed (pval < 0.05; FDR < 0.1) between the 27 matched brain mets and primary tumor pairs. Persistent enrichment of integrins and immune-related pathways were seen among the modulated genes. Also, STAT3 activation in brain mets compared to primary tumors may suggest the possibility of Jak or IL-6/IL-6R interactions as potential therapeutic targets. CONCLUSIONS: Our study shows significant modulation of driver pathways in BM when compared with matched PB tumors.