Combination Of Conventional Therapies And Antiandrogenic Treatments As A Succesful Tool For Triple Negative Breast Cancer (Tnbc) Treatment

Triple negative breast cancer (TNBC) patients do not benefit from conventional hormonal therapies due to the loss of expression of ER, PR, and HER2. Therefore, the usual adjuvant treatments for breast cancer, are not applied to TNBC. Recently, it has been found that approximately one third of TNBC tumours express androgen receptor (AR) and it is associated with better response to endocrine therapies. However, the prognostic value of AR expression in TNBC is still unclear. Therefore, in this preliminary study we evaluate the effectiveness of an anti-androgen treatment (bicalutamide) respect to conventional treatments (doxorubicin and lapatinib) in TNBC human cell lines and their corresponding xenografts. Briefly, SUM149, SUM159 and MDAMB231 TNBC cell lines were cultured in supplemented medium. Cells were plated in 96-well plates and a serial dilution of Doxorubicin, Lapatinib, Bicatulamide and respective combinations were added. In addition, 106 cells were implanted subcutaneosly into five female mice (Balb/C SCID). When tumors developed, mice were treated with doxorubicin, bicalutamide, doxorubicin + bicalutamide and doxorubicin + bicalutamide + lapatinib. Every treatment was perfomed every 3 days during 15 days and tumor reduction and appearance of metastases were evaluated. Results from cell culture showed that neoplasic cells from each cell line were high sensitive to bicalutamide treatment (SUM149 EC50: 9,860e009; MDAMB231 EC50: 9,454e009; SUM159 EC50: 2,170e009). Also, viability decreased when we added an anti-androgen (bicalutamide) to the conventional treatments (doxorubicin + lapatinib). In vivo experiments revealed a greater percentage of tumour reduction (around 70%) in mice treated with combination of treatments and a lower appearance of metastasis was observed in this group respect to control group (SUM149: 40% vs 60%; MDA-MB-231: 20% vs 75%; SUM159: 20% vs 60%). Therefore, our preliminary findings suggest that the addition of an anti-androgenic agent to treatments currently in use can reduce the tumour considerably, defining anti-androgenic treatments as a novel effective therapeutic target. Citation Format: Sara Caceres, Angela Alonso Diez, Gema Silvan, Maria J. Illera, Juan C. Illera. Combination of conventional therapies and antiandrogenic treatments as a succesful tool for triple negative breast cancer (TNBC) treatment [abstract]. In: Proceedings of the Annual Meeting of the American Association for Cancer Research 2020; 2020 Apr 27-28 and Jun 22-24. Philadelphia (PA): AACR; Cancer Res 2020;80(16 Suppl):Abstract nr 4362.