Abstract 169: Drug resistance gene expression pathways in primary refractory breast cancer

Purpose/Objective: Breast cancer is a collection of diseases with distinct molecular subtypes with differing prognoses. Clinically, there is a group of therapy resistant breast cancers characterized by resistance to conventional chemo- and radiotherapy with short overall survival and poor prognosis, which we termed primary refractory breast cancer (PRBC). We hypothesized that PRBC is characterized by specific genomic changes that may contribute to therapy resistance. The aim of this study was to identify changes in gene expression profiles of PRBC compared to triple negative (TNBC) and ER+/-PR positive (HR) breast cancer cohorts. Methods: PRBC was defined as patients with an initial diagnosis of Stage I-III breast cancer who either I) developed metastatic disease within 6 months of completing treatment or II) died of breast cancer within two years of initial diagnosis. Formalin-fixed paraffin-embedded (FFPE) tissue was obtained under an IRB approved protocol 01-13-43c. RNA was extracted from macro-dissected FFPE tumor tissue. Gene expression profiling was performed with Affymetrix Human Transcriptome Array 2.0 and gene signatures were analyzed using a single sample gene set enrichment methodology. Gene signatures of PRBC patients were compared to signatures of two TNBC and HR cohorts with gene expression data generated by identical methodology. Results: A total of nineteen samples from eight patients had sufficient tumor material to obtain RNA. The median age at diagnosis was 44.3 years, 62.5% were triple negative. At initial diagnosis the stage ranged from IA to IIIC. Sixty-three percent received neoadjuvant chemotherapy. The median time to relapse was 8.4 months and median time to death 1.7 years. Genomic analysis identified highly significant (p Conclusions: PRBC is characterized by significant upregulation of multiple gene expression signatures important in drug resistance including ABC transporters, hypoxia, AKT and DNA repair pathways. Confirmation of these results would allow the development of alternative treatment strategies for PRBC to help improve the devastatingly poor prognosis of this subgroup of patients. Citation Format: Charlene Kan, Shikha Parsai, Stefanie Avril, Janice Lyons, Hannah Gilmore, Junran Zhang, Lyndsay Harris. Drug resistance gene expression pathways in primary refractory breast cancer. [abstract]. In: Proceedings of the 107th Annual Meeting of the American Association for Cancer Research; 2016 Apr 16-20; New Orleans, LA. Philadelphia (PA): AACR; Cancer Res 2016;76(14 Suppl):Abstract nr 169.