Abstract 2296: Identification of novel nuclear receptor targets in estrogen receptor negative breast cancer

Abstract

Abstract Introduction: Estrogen receptor (ER)-negative breast cancer has a particularly poor prognosis, and there are limited targeted agents for this subtype. Aims and Methods: To identify nuclear receptor (NR) targets, we did microarray analysis of 227 ER-negative tumors as assessed by immunohistochemistry, and performed hierarchical clustering using 41 NRs, and prediction analysis of microarrays (PAM) across the clustered groups. Cell lines were matched to identified groups using previously published data. Clinical correlations were made using previously published breast cancer datasets. Results and Conclusion: The 41 NRs clustered the tumors into 5 distinct groups. We found that the androgen receptor (AR) was the highest ranked discriminator of these groups followed by ERα. Group 1 (14% of the tumors) was characterized by elevated ERRα and RXR expression. Group 2 (9%) was characterized by higher expression of the orphan receptor NURR1. Group 3 was the largest group (37%), and showed high level expression of PPARα. Group 4 (16%) expressed higher levels of PPARγ. Group 5 (24%) demonstrated particularly high relative expression of AR, and also showed higher expression of ERα and ERRα. We used previously published microarray data to match cell lines to the NR groups using the scoring matrix developed in the PAM analysis. These cell lines are currently being tested for response to NR agonists and antagonists in growth (MTT, soft-agar, mammosphere) and apoptotic assays. We used a previously published microarray data set with long-term follow up information to identify potential differences in outcomes for the different NR subtypes. While we found no significant differences between the groups, the sample size was quite low for each subtype (n∼15 per group). In summary, we have identified several novel ER-negative tumor groups by different expression level of NRs which may contribute to the prediction of breast cancer molecular subtypes. 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 2296. doi:10.1158/1538-7445.AM2011-2296