Predicting response to the anti-estrogen fulvestrant in recurrent ovarian cancer

Gynecol Oncol. 2013 Nov;131(2):368-73. doi: 10.1016/j.ygyno.2013.07.099. Epub 2013 Jul 30.


Background: Anti-estrogen therapy appears to have efficacy in a subset of ovarian cancers, as demonstrated in multiple phase II studies. Identifying sensitive patients early in treatment may allow for targeted, low-toxicity primary therapy or prevention of recurrence. We have previously demonstrated that the likelihood of response to letrozole could be improved by patient selection based on estrogen-pathway marker expression. We sought to identify ovarian cancer biomarkers that might indicate sensitivity to fulvestrant, an estrogen receptor antagonist.

Methods: Tissue samples from the primary tumors of patients enrolled in a phase II study of fulvestrant for the treatment of multiply-recurrent ovarian cancer were embedded randomly in a tissue microarray (TMA). Estrogen receptor alpha (ERα) expression was assessed by both conventional immunohistochemistry (IHC) and quantitative immunofluorescence (IF) (AQUA) while expression of 14 other estrogen-regulated markers was assessed by quantitative IF and correlated with clinical outcomes.

Results: Almost half of patients experienced clinical benefit (CR+PR+SD) at 90 days despite a median of 5 previous treatment regimens. 24 of 26 patient samples were available and included in the TMA. ERα expression, measured either by conventional IHC or by AQUA analysis, was associated with clinical benefit, while TFF1 and vimentin expression (measured by IF AQUA score) was predictive of progression-free survival.

Conclusions: These results confirm our previous observation that clinical ovarian cancer includes a subset of tumors with sensitivity to estrogen pathway blockade. Expression profile of sensitive tumors appears to be detectably different from insensitive tumors, suggesting that further improvements in treatment efficacy can be obtained through appropriate patient selection.

Keywords: Biological therapy; Endocrine therapy; Estrogen receptor; Fulvestrant; Ovarian cancer; Vimentin.

Publication types

  • Clinical Trial, Phase II
  • Observational Study
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Antineoplastic Agents, Hormonal / therapeutic use*
  • Estradiol / analogs & derivatives*
  • Estradiol / therapeutic use
  • Estrogen Antagonists / therapeutic use*
  • Estrogen Receptor alpha / analysis
  • Estrogen Receptor alpha / antagonists & inhibitors
  • Estrogen Receptor alpha / biosynthesis*
  • Female
  • Fluorescent Antibody Technique
  • Fulvestrant
  • Humans
  • Immunohistochemistry
  • Middle Aged
  • Neoplasm Recurrence, Local / drug therapy*
  • Neoplasm Recurrence, Local / metabolism
  • Ovarian Neoplasms / drug therapy*
  • Ovarian Neoplasms / metabolism
  • Tissue Array Analysis


  • Antineoplastic Agents, Hormonal
  • Estrogen Antagonists
  • Estrogen Receptor alpha
  • Fulvestrant
  • Estradiol