Distribution of G-protein coupled estrogen receptor in treatment-naive triple negative breast cancer and association with clinicopathologic characteristics

Background: G-protein coupled estrogen receptor (GPER) is a heptahelical transmembrane receptor that belongs to the G-protein coupled receptor superfamily and promotes specific estrogen binding and transactivation of epidermal growth factor receptors. GPER functions independently of estrogen receptors, ERα and ERβ, and it is commonly expressed in ER-negative breast tumors. Further evidence of its autonomy from ER is derived from the fact that GPER varies directly with advanced breast cancer, a relationship that is directly opposed to that shared by ER, indicating that GPER and ER are independent measures of estrogen responsiveness. Since triple negative breast cancer (TNBC) remains a high-risk subtype with a relative paucity of treatment options and a poorer prognosis compared to hormone receptor (HR) positive breast cancer, we have begun to evaluate GPER expression in TNBC tumors and to assess its correlation with clinicopathologic variables. Methods: Subjects diagnosed with breast cancer between 1996-2018 were identified using existing biorepositories at the University of Iowa. Inclusion criteria were patients diagnosed with TNBC with archived, treatment-naive breast tumor tissue and adequate clinical data from the electronic health record. Subjects were excluded if they did not meet both those criteria or they had stage IV disease at presentation. GPER expression was determined by immunohistochemistry (IHC) and a semiquantitative scoring system combining staining intensity and extent. Clinicopathologic variables included in the analysis were clinical stage, Elston-Ellis grade, BMI, and age. Comparisons between GPER staining scores and clinicopathologic characteristics were performed using chi-squared (Fisher’s exact where appropriate) and t-tests. Results: Of the 116 subjects we identified, 78 (67%) were GPER-positive. Most of the tumors were clinical stage T1 or T2 (85%) and node negative (79%) while 18% were N1. Breakdown by clinical stage is as follows: 2.6% stage 0, 42.2% stage I, 44% stage II, 6.8% stage III, and 4.3% unknown stage. Of the variables analyzed, clinical stage was found to be significant, with an inverse relationship observed between cancer stage and level of GPER expression (p=0.02). Conclusion: GPER is a potential therapeutic target for TNBC. The majority of TNBC tumors in our sample expressed GPER, a result which suggests that this subgroup of TNBC tumors may be responsive to estrogen-targeted therapy. In addition, correlating GPER expression with clinical outcome would evaluate its usefulness as a biomarker of risk for patients with very early stage TNBC tumors, a group in which personalized treatment options are presently not well defined. Citation Format: Sneha Phadke, Sarah Mott, Amani Bashir, Andrew Bellizzi, Murray Resnick, Ashlee Sturtevant, Edward Filardo. Distribution of G-protein coupled estrogen receptor in treatment-naive triple negative breast cancer and association with clinicopathologic characteristics [abstract]. In: Proceedings of the 2019 San Antonio Breast Cancer Symposium; 2019 Dec 10-14; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2020;80(4 Suppl):Abstract nr P2-11-16.