title: Antiestrogen therapy is active in selected ovarian cancer cases: the use of letrozole in estrogen receptor-positive patients.
abstract: OBJECTIVE
  To evaluate the efficacy of the aromatase inhibitor letrozole in preselected estrogen receptor (ER)-positive relapsed epithelial ovarian cancer patients and to identify markers that predict endocrine-sensitive disease.
  
  
  METHODS
  This was a phase II study of letrozole 2.5 mg daily until clinical or marker evidence of disease progression in previously treated ER-positive ovarian cancer patients with a rising CA125 that had progressed according to Rustin's criteria. The primary end point was response according to CA125 and response evaluation criteria in solid tumors (RECIST) criteria. Marker expression was measured by semiquantitative immunohistochemistry in sections from the primary tumor.
  
  
  RESULTS
  Of 42 patients evaluable for CA125 response, 7 (17%) had a response (decrease of >50%), and 11 (26%) patients had not progressed (doubling of CA125) following 6 months on treatment. The median time taken to achieve the CA125 nadir was 13 weeks (range 10-36). Of 33 patients evaluable for radiological response, 3 (9%) had a partial remission, and 14 (42%) had stable disease at 12 weeks. Eleven patients (26%) had a PFS of >6 months. Subgroup analysis according to ER revealed CA125 response rates of 0% (immunoscore, 150-199), 12% (200-249), and 33% (250-300); P = 0.028, chi(2) for trend. Expression levels of HER2, insulin-like growth factor binding protein 5, trefoil factor 1, and vimentin were associated with CA125 changes on treatment.
  
  
  CONCLUSIONS
  This is the first study of a hormonal agent in a preselected group of ER-positive ovarian cancer patients. A signature of predictive markers, including low HER2 expression, predicts response.
authors.affiliation: Cancer Research UK Centre, University of Edinburgh, Crewe Road South, Edinburgh, Scotland, United Kingdom. john.smyth@ed.ac.uk
authors.forename: John F
authors.initials: JF
authors.lastname: Smyth
authors.forename: Charlie
authors.initials: C
authors.lastname: Gourley
authors.forename: Graeme
authors.initials: G
authors.lastname: Walker
authors.forename: Melanie J
authors.initials: MJ
authors.lastname: MacKean
authors.forename: Alan
authors.initials: A
authors.lastname: Stevenson
authors.forename: Alistair R W
authors.initials: AR
authors.lastname: Williams
authors.forename: Awatif Al
authors.initials: AA
authors.lastname: Nafussi
authors.forename: Tzyvia
authors.initials: T
authors.lastname: Rye
authors.forename: Ron
authors.initials: R
authors.lastname: Rye
authors.forename: Moira
authors.initials: M
authors.lastname: Stewart
authors.forename: Janet
authors.initials: J
authors.lastname: McCurdy
authors.forename: Max
authors.initials: M
authors.lastname: Mano
authors.forename: Nick
authors.initials: N
authors.lastname: Reed
authors.forename: Tracey
authors.initials: T
authors.lastname: McMahon
authors.forename: Paul
authors.initials: P
authors.lastname: Vasey
authors.forename: Hani
authors.initials: H
authors.lastname: Gabra
authors.forename: Simon P
authors.initials: SP
authors.lastname: Langdon
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D014408:Biomarkers, Tumor / Q000032:analysis; D018394:CA-125 Antigen / Q000097:blood; D020847:Estrogen Receptor Modulators / Q000627:therapeutic use*; D005260:Female; D006801:Humans; D007150:Immunohistochemistry; D000077289:Letrozole; D008875:Middle Aged; D009364:Neoplasm Recurrence, Local / Q000097:blood / Q000188:drug therapy / Q000378:metabolism; D009570:Nitriles / Q000627:therapeutic use*; D010051:Ovarian Neoplasms / Q000097:blood / Q000188:drug therapy* / Q000378:metabolism*; D011960:Receptors, Estrogen / Q000378:metabolism*; D014230:Triazoles / Q000627:therapeutic use*
chemical_list: D014408:Biomarkers, Tumor; D018394:CA-125 Antigen; D020847:Estrogen Receptor Modulators; D009570:Nitriles; D011960:Receptors, Estrogen; D014230:Triazoles; D000077289:Letrozole