title: Clinical response to antiestrogen therapy in platinum-resistant ovarian cancer patients and the role of tumor estrogen receptor expression status.
abstract: OBJECTIVE
  This study aimed to determine the progression-free interval (PFI) for patients with platinum-resistant ovarian cancer on antiestrogen therapy (AET), and to correlate PFI with tumor estrogen receptor (ER) expression status.
  
  
  METHODS
  This single-institution retrospective cohort study investigated platinum-resistant epithelial ovarian, fallopian tube, and primary peritoneal cancers treated with tamoxifen or an aromatase inhibitor from January 1999 to January 2012. Median PFI was calculated and a 95% confidence interval was constructed by bootstrapping. Relationships of PFI with disease characteristics were examined using 1-way analysis of variance or Pearson correlation. Estrogen receptor status of tumor specimens was assessed by immunohistochemistry. Progression-free interval was compared between ER groups with the Mann-Whitney test. Kaplan-Meier estimate was used to determine overall survival.
  
  
  RESULTS
  Ninety-nine patients met inclusion criteria: 77 (78%) received tamoxifen and 22 (22%) an aromatase inhibitor. Patients had a mean of 4 prior chemotherapy regimens (range, 1-14). Median PFI for any AET was 4.0 months (range, 1-49; 95% confidence interval, 3.0-5.0). Progression-free interval was independent of the number of prior treatments and type of AET, but longer with earlier stage at diagnosis. Estrogen receptor status was obtained for 63 patients, 44 were positive and 19 were negative. Progression-free interval was not statistically significant between ER-positive (median, 4.0 months) and ER-negative (median, 2.0 months) tumor status (P = 0.36).
  
  
  CONCLUSIONS
  This is the largest study to date investigating AET in heavily pretreated, platinum-resistant ovarian cancer patients. The median PFI of 4.0 months is comparable to standard cytotoxic therapies, and some patients with PFI greater than this median interval had ER-negative tumors. Given the limited adverse effects of AET, as well as low cost including oral administration, this treatment should be considered in all patients with platinum-resistant ovarian cancer.
authors.affiliation: *Division of Gynecologic Oncology, †Center for Statistical Consultation and Research, and ‡Department of Pathology, University of Michigan, Ann Arbor, MI.
authors.forename: Marina
authors.initials: M
authors.lastname: Stasenko
authors.forename: Melissa
authors.initials: M
authors.lastname: Plegue
authors.forename: Andrew P
authors.initials: AP
authors.lastname: Sciallis
authors.forename: Karen
authors.initials: K
authors.lastname: McLean
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D047072:Aromatase Inhibitors / Q000627:therapeutic use; D000077216:Carcinoma, Ovarian Epithelial; D019008:Drug Resistance, Neoplasm / Q000187:drug effects*; D004965:Estrogen Antagonists / Q000627:therapeutic use*; D005185:Fallopian Tube Neoplasms / Q000188:drug therapy / Q000378:metabolism / Q000401:mortality; D005260:Female; D006801:Humans; D008875:Middle Aged; D009375:Neoplasms, Glandular and Epithelial / Q000188:drug therapy* / Q000378:metabolism / Q000401:mortality; D010051:Ovarian Neoplasms / Q000188:drug therapy* / Q000378:metabolism / Q000401:mortality; D010534:Peritoneal Neoplasms / Q000188:drug therapy / Q000378:metabolism / Q000401:mortality; D017671:Platinum Compounds / Q000627:therapeutic use*; D011960:Receptors, Estrogen / Q000378:metabolism / Q000502:physiology*; D012189:Retrospective Studies; D013629:Tamoxifen / Q000627:therapeutic use; D016896:Treatment Outcome; D055815:Young Adult
chemical_list: D047072:Aromatase Inhibitors; D004965:Estrogen Antagonists; D017671:Platinum Compounds; D011960:Receptors, Estrogen; D013629:Tamoxifen