Abstract 3605: The role of androgen receptor in invasive lobular breast carcinoma

Abstract

Abstract The leading problem for women with estrogen receptor α (ER) breast cancer – approximately 70% of all breast cancers – is that while the majority of tumors initially respond to anti-estrogen treatment including Tamoxifen and aromatase inhibitors, they will develop endocrine resistance. A histological subset of breast cancer called invasive lobular carcinoma (ILC) accounts for 15% of all breast cancer cases and approximately 90% of ILC are ER-positive. Despite clinical markers suggesting a better prognosis for ILC compared to the more common invasive ductal carcinoma (IDC), recent data suggests women with ILC develop Tamoxifen resistance at a higher rate than IDC. New strategies for treating hormone refractory tumors are needed that not only overcome anti-estrogen resistance, but also present a more tolerable side effect profile and have fewer dose-limiting toxicities than adjuvant chemotherapy. The majority of ER-positive breast cancers also express androgen receptor (AR) and while AR presence in breast cancer is controversial, increased expression of AR leads to Tamoxifen resistance in IDC cell lines. Since ILC has more AR expression than IDC, the role of AR in ILC was studied by treating cells with the non-aromatizable androgen dihydrotestosterone (DHT) and the synthetic androgen R1881 as well as the anti-androgen Enzalutamide. We have previously begun to characterize a Tamoxifen resistant variant of the ILC cell line Sum44PE termed LCCTam cells. In both Sum44PE and LCCTam cells, AR protein expression increases in response to androgens, an action that is blocked by Enzalutamide. Interestingly, androgens do not promote growth in ILC cells, but Enzalutamide is still able to inhibit growth. These results suggest Enzalutamide may be an effective alternative therapy for women with ILC. Future studies will focus on whether regulation of nuclear receptor co-factors influences differences in AR signaling in ILC. Citation Format: Hillary Stires, Rebecca B. Riggins. The role of androgen receptor in invasive lobular breast carcinoma [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2017; 2017 Apr 1-5; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2017;77(13 Suppl):Abstract nr 3605. doi:10.1158/1538-7445.AM2017-3605