Breast Cancer Research and Treatment

, Volume 123, Issue 1, pp 51–58 | Cite as

GPR30 and estrogen receptor expression: new insights into hormone dependence of inflammatory breast cancer

  • Hugo Arias-Pulido
  • Melanie Royce
  • Yun Gong
  • Nancy Joste
  • Lesley Lomo
  • Sang-Joon Lee
  • Nabila Chaher
  • Claire Verschraegen
  • Juanita Lara
  • Eric R. Prossnitz
  • Massimo Cristofanilli
Preclinical Study

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.

Keywords

Inflammatory breast cancer GPR30 Hormone receptors Growth factor receptors Overall survival Disease-free survival 

Supplementary material

10549_2009_631_MOESM2_ESM.pdf (20 kb)
Suppl. Fig. 1. Kaplan–Meier survival curves of OS (a) and DFS (b) time according to GPR30/ER patterns. (PDF 20 kb)
10549_2009_631_MOESM3_ESM.pdf (18 kb)
Suppl. Fig. 2. Kaplan–Meier survival curves of OS (a) and (b) time according to GPR30/ER status. (PDF 17 kb)
10549_2009_631_MOESM4_ESM.pdf (18 kb)
Suppl. Fig. 3. Kaplan–Meier survival curves of OS (a) and DFS (b) time according to ER status. (PDF 17 kb)

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Copyright information

© Springer Science+Business Media, LLC. 2009

Authors and Affiliations

  • Hugo Arias-Pulido
    • 1
  • Melanie Royce
    • 2
  • Yun Gong
    • 6
  • Nancy Joste
    • 3
  • Lesley Lomo
    • 3
  • Sang-Joon Lee
    • 4
  • Nabila Chaher
    • 7
  • Claire Verschraegen
    • 2
  • Juanita Lara
    • 6
  • Eric R. Prossnitz
    • 5
  • Massimo Cristofanilli
    • 6
  1. 1.Translational Therapeutics LaboratoryThe University of New Mexico Cancer CenterAlbuquerqueUSA
  2. 2.Division of Hematology/OncologyThe University of New Mexico Cancer CenterAlbuquerqueUSA
  3. 3.Department of PathologyThe University of New Mexico Cancer CenterAlbuquerqueUSA
  4. 4.Division of Epidemiology and BiostatisticsThe University of New Mexico Cancer CenterAlbuquerqueUSA
  5. 5.Cell Biology and PhysiologyThe University of New Mexico Cancer CenterAlbuquerqueUSA
  6. 6.Department of Pathology, and Breast Medical Oncology – The Morgan Welch Inflammatory Breast Cancer Research Program and ClinicThe University of Texas MD Anderson Cancer CenterHoustonUSA
  7. 7.Department of PathologyCentre Pierre et Marie CurieAlgiersAlgeria

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