Abstract 1341: Endocrine deprivation therapy increases the sensitivity of breast cancer cells to T cell-mediated lysis independently of estrogen receptor or androgen receptor status

Abstract

Abstract Estrogen deprivation therapy has been used as the first line adjuvant hormonal therapy for breast cancer for over 20 years. Tamoxifen, the first drug discovered to inhibit estrogen receptor signaling, is used to treat premenopausal women with estrogen receptor positive tumors. Although tamoxifen can be therapeutic in most women with estrogen receptor positive tumors, some women do not respond and others eventually develop resistance. In addition, tamoxifen has minimal effect on the growth of estrogen receptor negative tumors, including triple negative breast cancer, which has the poorest prognosis. Furthermore, prolonged administration of estrogen deprivation therapy can increase a patient's risk of developing secondary uterine/endometrial cancer, stroke and pulmonary embolism. As breast tumors develop resistant to estrogen deprivation therapy, in some cases, they can switch from estrogen to androgen-dependent growth. Recent studies have shown that enzalutamide, an androgen receptor signaling inhibitor, can reduce the growth of breast tumor cells regardless of their estrogen receptor status. We sought to determine if tamoxifen or enzalutamide could increase the sensitivity of breast tumor cells to T cell-mediated lysis, which would improve their therapeutic value by increasing the number of patients that could derive benefit from these therapies and possibly reducing the duration of treatment required for clinical benefit. We have observed that endocrine deprivation therapy, with either tamoxifen or enzalutamide, was able to increase the sensitivity of breast cancer cells to T cell-mediated killing and that this increased sensitivity occurs independently of estrogen or androgen receptor status. We have also been able to show that tamoxifen or enzalutamide increased the T cell-mediated killing of triple negative breast cancer cell lines, which are normally refractory to most standard treatments. Our hypothesis is that endocrine deprivation therapy has altered the expression of pro-apoptotic and anti-apoptotic genes leading to this increase in immune-mediated lysis. These data suggest that tamoxifen and enzalutamide may be useful in treating both estrogen/androgen receptor positive and estrogen/androgen receptor negative breast cancer, including triple negative breast cancer, when combined with immunotherapy. By combining endocrine deprivation therapy with cancer immunotherapy additional patients who may not have benefitted from the therapy alone may be able to achieve clinical benefit due to its synergistic activity with cancer immunotherapy. Citation Format: Anna R. Kwilas, Andressa Ardiani, Sofia R. Gameiro, James W. Hodge. Endocrine deprivation therapy increases the sensitivity of breast cancer cells to T cell-mediated lysis independently of estrogen receptor or androgen receptor status. [abstract]. In: Proceedings of the 106th Annual Meeting of the American Association for Cancer Research; 2015 Apr 18-22; Philadelphia, PA. Philadelphia (PA): AACR; Cancer Res 2015;75(15 Suppl):Abstract nr 1341. doi:10.1158/1538-7445.AM2015-1341