Abstract P3-05-07: Flutamide reduced tumor progression and altered steroid hormone secretion in human and canine inflammatory breast cancer cell lines

Abstract

Abstract Background: Inflammatory breast carcinoma (IBC) is a special type of breast cancer with a poor survival rate and accounts for 6% of diagnosed breast cancers. The role of androgens on breast cancer is on rise in research, trying to propose anti-androgen therapeutic strategies. The aim of this study was to determine the effects in vivo and in vitro of flutamide (anti-androgen drug) on cell proliferation, tumor progression and steroid production in two cancer IBC triple negative cell lines (SUM-149 and IPC-366, human and canine, respectively). Material and Methods: IPC-366 was cultured in Dulbecco's modified Eagle medium nutrient mixture F-12 Ham (DMEM/F12) and SUM149 was maintained in Ham's F-12 media. Flutamide concentrations added to the culture media were: 5 µm, 10 µm, and 15 µm for 72 hours. Additionally, IPC-366 and SUM149 xenotrasplanted mice were used for in vivo assays with the same flutamide concentrations administrated subcutaneously. Steroid hormones determination in culture media and tumor homogenates (pregnenolone (P5), progesterone (P4), dihydroepiandrostenedione (DHEA), androstenedione (A4), testosterone (T), dihydritestosterone (DHT), 17β-estradiol (E2) and estrone sulphate (SO4E1)) were assayed by EIA previously validated. Immunohistochemical (IHC) analysis of the steroidogenic enzymes CYP11A1, 3β-HSD, CYP19A1, 17β-HSD and 5α-reductase were assayed. Results: Percentage of cell proliferation showed a decrease in all treatments in IPC-366 and SUM149. In vivo tumor progression was reduced in around 65% in IPC-366 and SUM149 xenotrasplanted mice. Regarding hormonal secretion assayed in pellets and homogenates. in treated groups there was an increased in steroid secretion as showed the high levels found in P5, P4 and A4. T and DHT concentrations were higher in treated groups, in contrast to E2 levels that decreased. 17β-HSD and 5α-reductase by IHC showed a high expression in treated groups. Conclusion: IPC-366 and SUM149 treated with flutamide reduced the proliferation of neoplastic cells, reduced tumor progression in xenotrasplanted mice and altered steroid hormone secretion by increasing T production and decreasing in E2 levels. These results open a future approach for IBC and triple negative breast cancer. Citation Format: Caceres S, Pena L, Silvan G, Illera MJ, Monsalve B, Woodward WA, Reuben J, Illera JC. Flutamide reduced tumor progression and altered steroid hormone secretion in human and canine inflammatory breast cancer cell lines [abstract]. In: Proceedings of the 2016 San Antonio Breast Cancer Symposium; 2016 Dec 6-10; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2017;77(4 Suppl):Abstract nr P3-05-07.