Gene expression analysis for prediction of early brain metastasis (BM) in HER2-positive (HER2+) breast cancer patients (pts)

Abstract

1019 Background: BM is a common occurrence in HER2+ breast cancer pts. If the pts most likely to develop BM could be identified, prophylactic strategies might prevent or delay occurrence of this failure. We explored gene expression differences between HER2+ breast cancers with early vs late occurrence of BM. Methods: Study group included 90 HER2+ breast cancer pts, 43 of whom developed BM (BM+): 22 and 21 pts with <3 and >3 yrs in time from diagnosis to BM, respectively; 47 patients had not developed BM (BM-) at the last follow-up. We performed cDNA-mediated annealing, selection, extension, and ligation (DASL) assay (Illumina Corp) for expression of 502 known cancer genes using 200 ng RNA from archived FFPET. T-test with unequal variances was applied after sample median normalization. Differentially expressed genes were analyzed using Ingenuity Pathway Analysis. Results: A binary comparison of BM+ vs BM- revealed 25 differentially expressed genes (p <0.05). For BM+ in <3 yrs vs >3 yrs comparison, 95 genes were differentially expressed with a p value <0.05. Up-regulated gene pathways included Glucocorticoid Receptor, PI3K/AKT & PTEN, IGF-1, P53 and NF-κB. Down-regulated gene pathways were cell cycle G1/S checkpoint regulation, cell-cycle G2/M DNA damage checkpoint, Vitamin D and retinoic acid receptor signaling. Conclusions: Early BM occurrence in HER-2+ breast cancer pts can be predicted by gene expression in primary tumors. Altered cell cycle regulation seems to be particularly important. Analyses are ongoing to generate a gene-expression signature to predict development of BM. No significant financial relationships to disclose.