A new estrogen receptor on ER-negative breast cancer?

Abstract

10604 Background: Premenopausal women and BRCA-1 mutation carriers have estrogen receptor-negative (ER-) breast cancers that paradoxically seem responsive to hormonal deprivation such as oophorectomy. GPR30 is a G protein-coupled receptor that is activated not only by estradiol but also tamoxifen and fulvestrant. The prevalence and significance of GPR30 in breast cancer are unknown. We hypothesized that GPR30 may be present in ER-negative tumors and may promote growth of ER-negative breast cancer in premenopausal patients. Methods: An immunohistochemical staining protocol for rabbit polyclonal GPR30 antibody (Novus Biological) was developed initially on the known GPR30-positive breast cancer cell line MCF-7 and the GPR30-negative breast cancer cell line MDA-MB-231 and later on a panel of human breast tumors from archived paraffin blocks. After an automated protocol was optimized, under an IRB-approved protocol all incoming breast cancer specimens were stained for GPR30 and reviewed by a pathologist blinded to the ER/PR status. Significance of associations was tested by chi square analysis. Results: Twenty-seven breast cancer tumors were studied. The mean age of the patients was 53 (range 20–87). All of 10 triple negative (ER-,PR-, HER2 neu-) and 2 ER-/Her2 neu+ tumors stained positive for GPR30. Only 4 of 11 ER+/Her2neu - tumors stained positive for GPR30 (p=0.004). The mean age of triple negative patients was 43.7 yr, while the mean age of ER+/Her2 neu- was 63.2 (p=0.02). Three out of 4 ER+/HER2 neu+ tumors stained positive for GPR30. Four patients were African Americans, 2 had triple negative tumors and 2 ER+/Her2+, all 4 were positive for GPR30. Conclusions: GPR30 appears to be frequently expressed in ER-negative breast cancer and may represent an adverse factor. ER+ tumors with good prognostic features (PR+, HER2 neu-) were mostly negative for GPR30, while high-risk tumors were positive for GRP30. Premenopausal status and African-American race are known risk factors for lower survival. In this study, the African-American patients had high-risk tumors that were also positive for GPR30. A longer- range study is needed to test the association of GPR30 expression with recurrence and death. Future studies to assess the function of GPR30 in breast cancer cells may yield prognostic and therapeutic applications. No significant financial relationships to disclose.