Michel van Kruchten1, Pauline van der Marel1, Linda de Munck2, Harry Hollema3, Henriette Arts4, Hetty Timmer-Bosscha1, Elisabeth de Vries1, Geke Hospers1, Anna Reyners5. 1. Department of Medical Oncology, University of Groningen, University Medical Center Groningen, Groningen, The Netherlands. 2. Department of Registration and Research, Comprehensive Cancer Center the Netherlands, Utrecht, The Netherlands. 3. Department of Pathology, University of Groningen, University Medical Center Groningen, Groningen, The Netherlands. 4. Department of Gynecology, Division of Gynecologic Oncology, University of Groningen, University Medical Center Groningen, Groningen, The Netherlands. 5. Department of Medical Oncology, University of Groningen, University Medical Center Groningen, Groningen, The Netherlands. Electronic address: a.k.l.reyners@umcg.nl.
Abstract
OBJECTIVE:Androgen receptor (AR), estrogen receptor α and β (ERα, ERβ), and progesterone receptor (PR) are potential therapeutic targets in epithelial ovarian cancer. In this study we evaluate the prognostic value of these hormone receptors in ovarian cancer patients. METHODS: In a prospective multicenter randomized controlled phase II trial 196 ovarian cancer patients were randomized to carboplatin/docetaxel±celecoxib. Of 121 patients sufficient tumor tissue was available for hormone receptor analysis. Tissue micro-arrays were stained for AR, ERα, ERβ, and PR. Cluster analysis was performed to identify subgroups based on hormone receptor expression profile. Receptor expression was correlated to progression-free survival (PFS) and overall survival (OS) in uni- and multivariate analysis. RESULTS:AR, ERα, ERβ, and PR were expressed in respectively 10%, 31%, 73%, and 19%. In patients with synchronous metastasis tissue available (n=69 patients), discordant receptor expression was observed in 9-32%. ERβ-expression was associated with poor PFS and OS (hazard ratios 1.88 and 1.92). Clustering analysis revealed a subgroup with hormone receptor negative disease that had a favorable PFS and OS. CONCLUSION: Hormone receptors are expressed in the majority of ovarian cancer tumors and may serve as therapeutic targets. Clustering analysis can reveal subgroups with different outcome, which may prove valuable in selecting patients for endocrine therapy.
RCT Entities:
OBJECTIVE:Androgen receptor (AR), estrogen receptor α and β (ERα, ERβ), and progesterone receptor (PR) are potential therapeutic targets in epithelial ovarian cancer. In this study we evaluate the prognostic value of these hormone receptors in ovarian cancerpatients. METHODS: In a prospective multicenter randomized controlled phase II trial 196 ovarian cancerpatients were randomized to carboplatin/docetaxel±celecoxib. Of 121 patients sufficient tumor tissue was available for hormone receptor analysis. Tissue micro-arrays were stained for AR, ERα, ERβ, and PR. Cluster analysis was performed to identify subgroups based on hormone receptor expression profile. Receptor expression was correlated to progression-free survival (PFS) and overall survival (OS) in uni- and multivariate analysis. RESULTS:AR, ERα, ERβ, and PR were expressed in respectively 10%, 31%, 73%, and 19%. In patients with synchronous metastasis tissue available (n=69 patients), discordant receptor expression was observed in 9-32%. ERβ-expression was associated with poor PFS and OS (hazard ratios 1.88 and 1.92). Clustering analysis revealed a subgroup with hormone receptor negative disease that had a favorable PFS and OS. CONCLUSION: Hormone receptors are expressed in the majority of ovarian cancer tumors and may serve as therapeutic targets. Clustering analysis can reveal subgroups with different outcome, which may prove valuable in selecting patients for endocrine therapy.
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