Abstract 3489: In silico analysis of angiogenesis pathway as a prognostic tool in breast cancer

Abstract

Abstract Gene expression profiling studies have enabled us to study breast cancer biology at a molecular level. Studies have been geared at identifying better and comprehensive prognostic markers for the development of targeted therapeutics. With the growing use of anti-angiogenic agents as second line agents, we aim to study the prognostic role of angiogenesis related genes through retrospective analyses of publicly available breast cancer gene expression datasets. Three gene expression datasets from studies by van't Veer et al, Sorlie et al., and Sotiriou et al were analyzed. The data was downloaded from the BRB Array Tools archives and analyzed using BRB Array Tools. Since, we were particularly interested in genes related to angiogenesis; we selected the (CGAP) angiogenesis subset for the purpose of survival analyses. Two endpoints, overall survival (OS) and relapse free survival (RFS), were analyzed. Data for OS was not available for van't Veer et al. A subset analysis for estrogen receptor positive cases was performed. HIF1A was prognostic for OS and RFS in all datasets. VEGF was associated with survival only in ER+ cases. EGFR is prognostic for RFS but not OS. Several other angiogenesis genes were noted to affect prognosis in terms of OS and RFS (Table 1). Analysis of other publically available datasets will be undertaken to further validate these findings in ER+ and negative subgroups of breast cancer. These analyses highlight the importance of VEGF as an important marker among ER+ breast cancer patients. Thus, anti-angiogenic agents targeting VEGF may appear to play an important therapeutic role in this subset of patients. The analysis provides additional evidence of the importance of HIF1A in breast cancer. This may help identifying sub-populations of breast cancer that are most likely to respond to targeted therapies. Further immunohistochemical validation in in-vitro models will be performed. Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 102nd Annual Meeting of the American Association for Cancer Research; 2011 Apr 2-6; Orlando, FL. Philadelphia (PA): AACR; Cancer Res 2011;71(8 Suppl):Abstract nr 3489. doi:10.1158/1538-7445.AM2011-3489