Abstract 2272: Association of G-protein estrogen receptor (GPER) in primary breast cancer in Caucasian and Black women by tumor immunophenotype and menopausal status
Authors: Deming-Halverson Sandra L. , Graeber Carl , Machan Jason , Sabo Edmond , Zheng Wei , Filardo Edward J. 
Published: July 2016

Background: Assignment of breast cancer therapies is largely defined by immunohistochemical analyses that evaluate steroid hormone and growth factor receptor status in primary tumor biopsies. Patients whose tumors are devoid of these receptors have fewer treatment options, and poor survival. This outcome is more commonly measured among Black versus Caucasian patients, and in patients with intact ovarian function. The G-protein coupled estrogen receptor, GPER, holds significance for breast cancer biology and treatment as 17β-estradiol and ER antagonists trigger the release of epidermal growth factor (EGF)-ligands and GPER associates directly with clinicopathological factors that predict advanced disease.

Experimental design: GPER was measured by immunohistochemical analysis and a semi-quantitative scoring method in 521 primary breast tumors obtained from the NCI Cooperative Breast Cancer Tissue Resource and the Nashville Breast Health Study, including tumor specimens derived from 389 Caucasian and 108 Black patients. GPER was correlated with disease progression variables and evaluated by race, menopausal status and tumor immunophenotype.

Results: GPER is expressed in more than two-thirds of invasive breast carcinomas in this study with no difference observed between Caucasian and Black women (p = 0.69). Coexpression of GPER and ER was measured in less than half of all tumors (48%). Additionally, GPER is commonly expressed in ER-negative tumors (107/171; 62%) and in triple negative breast cancer (TNBC) (42/56; 75%) and did not differ by race for this newly defined measure of estrogen responsiveness (p = 0.42). Moreover, while ER-negative tumors are more common in pre- (79/153; 52%) versus postmenopausal women (92/336; 27%), GPER expression is not influenced by menopausal status. GPER is positively associated with tumor size (particularly in premenopausal women) in both studies, and with frank metastases at first diagnosis in the NCI population. No significant association was seen with nodal invasion. Survival data in NBHS patients found that women who died of breast cancer are more likely to have GPER-positive tumors than survivors.

Conclusion: GPER is expressed in the majority of invasive breast tumors (&gt; 60%) at diagnosis and is commonly retained in patients with ER-negative or triple-negative disease regardless of race or menopause. Unlike ER, which varies inversely with variables that predict advanced disease, GPER is positively associated with these same prognostic parameters. These data support GPER as an independent marker of estrogen responsiveness and breast cancer progression. Most importantly, our results suggest that GPER represents a promising therapeutic target since its expression is constant across multiple types of invasive breast cancer, including patients with TNBC and in tumors from pre- and postmenopausal women.

Citation Format: Sandra L. Deming-Halverson, Carl Graeber, Jason Machan, Edmond Sabo, Wei Zheng, Edward J. Filardo. Association of G-protein estrogen receptor (GPER) in primary breast cancer in Caucasian and Black women by tumor immunophenotype and menopausal status. [abstract]. In: Proceedings of the 107th Annual Meeting of the American Association for Cancer Research; 2016 Apr 16-20; New Orleans, LA. Philadelphia (PA): AACR; Cancer Res 2016;76(14 Suppl):Abstract nr 2272.