Efficacy of Anti-Estrogen Therapy in Estrogen Receptor Positive High-Grade Serous Ovarian Carcinoma: A Systematic Review

Author(s): Phyllis van der Ploeg, Meggy P.M. Ottenheijm, Laura A.M. van Lieshout, Anja van de Stolpe, Steven L. Bosch, Anna M.J. Thijs, Ruud L.M. Bekkers, Jurgen M.J. Piek

Therapy targeting the estrogen receptor (ER) pathway is being explored as a treatment option in ovarian carcinoma. However, studies on the efficacy of anti-estrogen therapy include a broad range of histological subtypes and/or do not select patients based on ER status. This systematic review provides an analysis of literature on the clinical benefit rate (CBR) of anti-estrogen therapy in ER positive high-grade serous carcinomas (HGSC) and on the correlation between ER expression by immunohistochemistry and clinical response. We did not find studies with populations consisting solely of ER positive HGSC. However, we included six studies reporting on 407 evaluable patients of whom 376 were HGSC (92%) and 302 were confirmed ER positive (80%). Anti-estrogen therapy resulted in a CBR of 27-65% and an overall response rate of 0-16%. No correlation was found between ER expression and clinical response. Therefore, ER protein expression alone is not a specific predictor of response. This may result from the incorrect assumption that ER expression equals ER pathway activity, since in the absence of ER activating mutations, ER pathway activity depends on availability of the estradiol ligand. In order to apply effective ER targeted therapy, it is important to develop better predictors to identify (non)-responders.