Abstract 5691: Significance of combination treatment of antiprogestin and aromatase inhibitors in aromatase overexpressing T47D breast cancer cells

Treatment with aromatase inhibitors (AI) is considered as the first line of treatment for ER+PR+ cancers. However, many patients acquire resistance to aromatase inhibitors. Therefore, there is a need for new approaches to overcome resistance to AI in these patients. In the present study we determined the effects of third generation AI in genetically engineered high aromatase overexpressing T47Darom cells. Treatment of T47Darom cells with Leterozole (L), Anastrazole(A) and Exemestane(E) at 5μM concentration exhibited inhibition of 32% 19% and 18% respectively, however, in combination with proellex overall inhibition increased to 50% suggesting additive effect of proellex along with aromatase inhibitor. Interestingly, Proellex showed dose-dependent inhibition of T47Darom cells incubated with testosterone (1nM and 10nM) suggesting that Proellex also has aromatase inhibitory property. Furthermore, Proellex inhibited cell proliferation of both ER/PR positive (T47D and T47Darom) and ER/PR negative (MDA-MB231cells). These results suggested that the mechanism of action may not be entirely dependent to PR status. Since both T47Darom and MDA-MB231 cells exhibit increased COX2 expression and increased COX2 expression has been associated with enhanced cell proliferation and malignancy in breast cancer, we determined the effects of Proellex on COX2 expression. Results showed that in both these cell lines COX2 expression was decreased as determined by real-time PCR when the cells were treated with Proellex at 10−6M. These studies suggest that Proellex either alone or in combination with aromatase inhibitors may provide a new treatment strategy for breast cancer patients.(This work is supported by Repros Therapeutics) Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 101st Annual Meeting of the American Association for Cancer Research; 2010 Apr 17-21; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2010;70(8 Suppl):Abstract nr 5691.