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

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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.

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Acknowledgments

Supported in part by NIH grant CA116662 (E.R.P.) and by New Mexico State IBC funding (New Mexico Senate Bill 532) and the State of Texas Inflammatory Breast Cancer Rider. We would like to thank the MDACC (Houston, TX) Human Tissue Repository for providing tissue samples and clinical data; Dr. A. Chakerian (EPL, Pathology, UNM) and T. Howard (Cell Biology and Physiology, UNM) for technical support with the IHC assays.

Author information

Authors and Affiliations

  1. Translational Therapeutics Laboratory, The University of New Mexico Cancer Center, Albuquerque, NM, USA

    Hugo Arias-Pulido

  2. Division of Hematology/Oncology, The University of New Mexico Cancer Center, Albuquerque, NM, USA

    Melanie Royce & Claire Verschraegen

  3. Department of Pathology, The University of New Mexico Cancer Center, Albuquerque, NM, USA

    Nancy Joste & Lesley Lomo

  4. Division of Epidemiology and Biostatistics, The University of New Mexico Cancer Center, Albuquerque, NM, USA

    Sang-Joon Lee

  5. Cell Biology and Physiology, The University of New Mexico Cancer Center, Albuquerque, NM, USA

    Eric R. Prossnitz

  6. Department of Pathology, and Breast Medical Oncology – The Morgan Welch Inflammatory Breast Cancer Research Program and Clinic, The University of Texas MD Anderson Cancer Center, Houston, TX, USA

    Yun Gong, Juanita Lara & Massimo Cristofanilli

  7. Department of Pathology, Centre Pierre et Marie Curie, 1, Avenue Battendier, Place May 1st, Algiers, Algeria

    Nabila Chaher

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  1. Hugo Arias-Pulido
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  2. Melanie Royce
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  3. Yun Gong
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  4. Nancy Joste
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  5. Lesley Lomo
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  8. Claire Verschraegen
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  9. Juanita Lara
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  10. Eric R. Prossnitz
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  11. Massimo Cristofanilli
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Corresponding authors

Correspondence to Hugo Arias-Pulido or Melanie Royce.

Additional information

Hugo Arias-Pulido and Yun Gong contributed equally to this work.

Melanie Royce and Massimo Cristofanilli equally contributed as senior investigators in this study.

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Arias-Pulido, H., Royce, M., Gong, Y. et al. GPR30 and estrogen receptor expression: new insights into hormone dependence of inflammatory breast cancer. Breast Cancer Res Treat 123, 51–58 (2010). https://doi.org/10.1007/s10549-009-0631-7

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  • DOI: https://doi.org/10.1007/s10549-009-0631-7

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