Abstract 1828: RNA-seq reveals association of pCR and changes in lncRNA expression in pre-operative bevacizumab treatment of breast cancer

Background: Long non-coding RNAs (lncRNAs) are pervasively transcribed in the genome yet their role in human disease is not well understood. Recent studies show that expression of the lncRNA HOTAIR is increased in primary breast tumors and is a predictor of metastasis. However, to date, it is unclear how changes in lncRNA expression with treatment correlate with response. We performed an RNA-seq study to characterize changes in lncRNA expression following exposure to chemotherapy or biologic therapy and evaluate association to achievement of pathologic complete response (pCR) to neoadjuvant therapy. Methods: We sequenced transcriptomes of core biopsy RNA from 50 pairs of breast tumors obtained from neoadjuvant clinical trials BrUOG 211A/211B. Patients were given a run-in dose of bevacizumab (B), nab-paclitaxel (N) or trastuzumab (T), followed by combination biologic/chemotherapy (HER2- with B/carboplatin/N; HER2+ with T/carboplatin/N). RNA was derived from biopsy pairs obtained pre/post 10 day exposure to run-in monotherapy. Paired-end sequencing was performed with 74bp read length, yielding genome-wide transcriptomic data. Transcriptomic abundance and differential expression were estimated assuming Poisson-distributed read-counts. Paired-end sequence data was aligned to a lncRNA database containing 14,572 unique lncRNAs. Changes in relative abundance of lncRNA transcripts were tested for association with pCR using the Wilcoxon rank-sum test. Results: On average, in each patient 1500 lncRNAs were differentially expressed between pre and post samples (p