title: Predicting response to the anti-estrogen fulvestrant in recurrent ovarian cancer.
abstract: 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.
authors.affiliation: Division of Gynecologic Oncology, Department of Obstetrics and Gynecology, University of Minnesota, Minneapolis, MN, USA. Electronic address: argenta@umn.edu.
authors.forename: Peter A
authors.initials: PA
authors.lastname: Argenta
authors.forename: Inhwa
authors.initials: I
authors.lastname: Um
authors.forename: Charlene
authors.initials: C
authors.lastname: Kay
authors.forename: David
authors.initials: D
authors.lastname: Harrison
authors.forename: Dana
authors.initials: D
authors.lastname: Faratian
authors.forename: Thanasak
authors.initials: T
authors.lastname: Sueblinvong
authors.forename: Melissa A
authors.initials: MA
authors.lastname: Geller
authors.forename: Simon P
authors.initials: SP
authors.lastname: Langdon
mesh_terms: D005260:Female; D006801:Humans; D008875:Middle Aged; D018931:Antineoplastic Agents, Hormonal / Q000627:therapeutic use; D004958:Estradiol / Q000031:analogs & derivatives / Q000627:therapeutic use; D004965:Estrogen Antagonists / Q000627:therapeutic use; D047628:Estrogen Receptor alpha / Q000032:analysis / Q000037:antagonists & inhibitors / Q000096:biosynthesis; D005455:Fluorescent Antibody Technique; D000077267:Fulvestrant; D007150:Immunohistochemistry; D009364:Neoplasm Recurrence, Local / Q000188:drug therapy / Q000378:metabolism; D010051:Ovarian Neoplasms / Q000188:drug therapy / Q000378:metabolism; D046888:Tissue Array Analysis; D017322:Clinical Trials, Phase II as Topic
chemical_list: D018931:Antineoplastic Agents, Hormonal; D004958:Estradiol; D004965:Estrogen Antagonists; D047628:Estrogen Receptor alpha; D000077267:Fulvestrant
keywords: Biological therapy; Endocrine therapy; Estrogen receptor; Fulvestrant; Ovarian cancer; Vimentin