Abstract 5281: Increased androgen secreted levels promote anti-proliferative effects on triple negative breast cancer

Abstract

Abstract Endocrine therapies present poor effectivity in triple negative breast cancer (TNBC) but the reason is still unknown. However, in vitro experiments suggested that these therapies could be beneficial for inflammatory breast cancer, the most aggressive type of breast cancer. For this reason, the aim of this study is to determine why these therapies had poor effectiveness on TNBC. To this purpose, we evaluated the efficacy of Dutasteride (a 5α-Reductase inhibitor) and Anastrozole (an aromatase inhibitor) in three TNBC cell lines, SUM-149, SUM-159 and MDA-MD-231; and another no TNBC cell line, MCF-7. Sensitivity, proliferation and hormone secretion of estrone sulfate (E1SO4), estradiol (E2), testosterone (T) and dehydrotestosterone (DHT) was performed. Firstly, it was realized a sensitivity assay for determinate the half-maximal effective concentration (EC-50) of the two compounds in vitro. The results obtained from this aasay revealed an effective concentration of 1μM for each compound. Then, a cell proliferation assay was performed. Cells were seeded in 96-well plates with 1μM concentration of Dutasteride and Anastrozole for 24h. After, media was collected in order to determine hormone secretion of E1SO4, E2, T and DHT by an amplified enzymeimmunoassay. Our results revealed a significant reduction of 50% approximately in the TNBC cell lines for both treatments, except in MDA-231, which was more resistant, decreasing its proliferation in approximately 20%. However, the MCF-7 cell line had increased around 20% its proliferation. Regarding hormonal secretion, Dutasteride and Anastrozole treatments promoted a significant increase in T and DHT levels in TNBC cell lines while in MCF-7 a significant decreased was observed. Therefore, the increased on androgen secretion is related with the anti-proliferative effects of Dutasteride and Anastrozole in TNBC cell lines. However, both treatments also resulted in an increased on E1SO4 and E2 levels in all cell lines, being this increase greater in MCF-7. Therefore, although endocrine therapies could be effective in in vitro conditions, cells would be able to secret estrogens in order to survive and proliferate and limiting the effectiveness of these treatments. In conclusion, dutasteride and anstrozole promote a reduction in cell proliferation by increasing the secreted levels of androgens. The combination of these treatments with potent inhibitors of estrogen secretion may result in a promising treatment for TNBC. Citation Format: Sara Caceres, Belen Crespo, Angela Alonso-Diez, Gema Silvan, Josefina M. Illera, Alejandro Pascual, Maria J. Herrera, Miriam De La Puente, Juan Carlos Illera. Increased androgen secreted levels promote anti-proliferative effects on triple negative breast cancer [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2022; 2022 Apr 8-13. Philadelphia (PA): AACR; Cancer Res 2022;82(12_Suppl):Abstract nr 5281.