title: GPR30 and estrogen receptor expression: new insights into hormone dependence of inflammatory breast cancer.
abstract: GPR30 is a novel G protein-coupled estrogen receptor (ER) associated with metastases in breast cancer (BC) and poor survival in endometrial and ovarian tumors. The association of GPR30 expression with inflammatory breast cancer (IBC), an aggressive and commonly hormone-independent form of BC, has not been studied. GPR30, ER, progesterone receptor (PR), epidermal growth factor receptor (EGFR), and HER-2 expression were assessed by immunohistochemistry (and FISH for HER-2) in 88 primary IBCs. GPR30 expression was correlated with patient overall survival (OS), disease-free survival (DFS), pathologic variables, and other biomarkers. GPR30 expression was found in 69% of IBC cases. ER, PR, HER-2, and EGFR were found in 43, 35, 39, and 34% of IBC cases, respectively. GPR30 expression correlated inversely with ER expression (P = 0.02). Co-expression of ER and GPR30 was found in 24% of IBC samples; 19% expressed only ER and 46% expressed only GPR30. Univariate analysis showed no association between GPR30 expression and OS or DFS. However, co-expression of ER and GPR30 was associated with improved OS (P < 0.03) and marginally with DFS (P < 0.06); the absence of both ER and GPR30 was associated with worse OS and DFS (P = 0.03 for both). Multivariate analysis identified ER as an independent prognostic factor of OS (P = 0.008) and DFS (P = 0.02). The majority of IBC tumors are GPR30-positive, suggesting that estrogen signaling may be active in ER-negative IBC patients. These findings suggest potential new therapeutic targets for IBC such as novel endocrine agents or direct modulation of GPR30.
authors.affiliation: Translational Therapeutics Laboratory, The University of New Mexico Cancer Center, Albuquerque, NM, USA. harias@salud.unm.edu
authors.forename: Hugo
authors.initials: H
authors.lastname: Arias-Pulido
authors.forename: Melanie
authors.initials: M
authors.lastname: Royce
authors.forename: Yun
authors.initials: Y
authors.lastname: Gong
authors.forename: Nancy
authors.initials: N
authors.lastname: Joste
authors.forename: Lesley
authors.initials: L
authors.lastname: Lomo
authors.forename: Sang-Joon
authors.initials: SJ
authors.lastname: Lee
authors.forename: Nabila
authors.initials: N
authors.lastname: Chaher
authors.forename: Claire
authors.initials: C
authors.lastname: Verschraegen
authors.forename: Juanita
authors.initials: J
authors.lastname: Lara
authors.forename: Eric R
authors.initials: ER
authors.lastname: Prossnitz
authors.forename: Massimo
authors.initials: M
authors.lastname: Cristofanilli
mesh_terms: D000328:Adult; D000368:Aged; D014408:Biomarkers, Tumor / Q000032:analysis*; D001943:Breast Neoplasms / Q000378:metabolism* / Q000401:mortality / Q000473:pathology; D018572:Disease-Free Survival; D066246:ErbB Receptors / Q000096:biosynthesis; D005260:Female; D006801:Humans; D007150:Immunohistochemistry; D017404:In Situ Hybridization, Fluorescence; D053208:Kaplan-Meier Estimate; D008875:Middle Aged; D009367:Neoplasm Staging; D016016:Proportional Hazards Models; D018719:Erb-b2 Receptor Tyrosine Kinases / Q000096:biosynthesis; D011960:Receptors, Estrogen / Q000096:biosynthesis*; D043562:Receptors, G-Protein-Coupled / Q000096:biosynthesis*; D011980:Receptors, Progesterone / Q000096:biosynthesis; D055815:Young Adult
chemical_list: D014408:Biomarkers, Tumor; D066246:ErbB Receptors; D018719:Erb-b2 Receptor Tyrosine Kinases; D011960:Receptors, Estrogen; D043562:Receptors, G-Protein-Coupled; D011980:Receptors, Progesterone; C109584:GPER1 protein, human; C512478:EGFR protein, human