No abstract

Purpose:The seven transmembrane receptor, GPR30, is linked to estrogen binding and heparanbound epidermal growth factor release. Here, the significance of GPR30 in human breast cancer was evaluated by comparing its relationship to steroid hormone receptor expression and tumor progression variables. Experimental Design: Immunohistochemical analysis of a National Cancer Instituteŝ ponsored tumor collection comprised of 361 breast carcinomas obtained at first diagnosis (321 invasive and 40 intraductal tumors). Biopsies from 12 reduction mammoplasties served as controls. The distribution pattern of GPR30, estrogen receptor (ER), and progesterone receptor (PR) was correlated with clinicopathologic variables obtained at diagnosis. Results: GPR30, ER, and PR were positive in all 12 normal controls. In contrast, GPR30 expression varied in breast tumors, in which 62% (199 of 321) of invasive tumors and 42% (17 of 40) of intraductal tumors were positive. Codistribution of ER and GPR30 was measured in 43% (139 of 321) of invasive breast tumors, whereas both receptors were lacking (ER(61of 321) of the tumors analyzed, indicating a significant association between ER and GPR30 (P < 0.05).The coexpression of PR and ER did not influence GPR30 expression, yet coexpression of GPR30 and ER was linked to PR positivity. Unlike ER, which varied inversely with HER-2/neu and tumor size, GPR30 positively associated with HER-2/neu and tumor size. In addition, GPR30 showed a positive association with metastasis (P = 0.014; odds ratio, 1.9). Conclusions: GPR30 and ER exhibited distinct patterns of association with breast tumor progression variables, including HER-2/neu, tumor size, and metastatic disease. Thus, these results support the hypothesis that GPR30 and ER have an independent influence on estrogen responsiveness in breast carcinoma.Estrogen promotes the development and homeostasis of the mammary gland, and the growth of tumors that arise from this tissue. It is widely accepted that estrogen manifests its physiologic and pathophysiologic actions through its interaction with specific receptors. Estrogen receptor (ER) a and its structural homologue, ERh, belong to the nuclear steroid hormone family, and function indisputably as hormonedependent transcription factors. The blockade of estrogenbinding sites on the ER has proven to be an effective means to inhibit the growth of breast tumors expressing ER, and today, this modality of treatment remains the standard endocrine therapy for ER + tumors. Although there is general concordance between ER expression and responsiveness to ER antagonism, as indicated in greater disease-free survival at 5-year follow-up for postmenopausal patients with ER + tumors receiving tamoxifen (1), roughly one in four patients do not respond to tamoxifen therapy. A variety of explanations have been offered to account for nonresponsiveness to ER antagonism, including: (a) intratumoral heterogeneity in ER expression, (b) evolution of mutant ERs with reduced affinity for ER antagonists, (c) drug resista...