title: Treatment with olaparib in a patient with PTEN-deficient endometrioid endometrial cancer.
abstract: BACKGROUND
  A 58-year-old woman presented with metastatic endometrioid endometrial adenocarcinoma after being previously treated with surgery and adjuvant radiotherapy for early-stage endometrial cancer. She had received several lines of chemotherapy for multiple relapses over 9 years and displayed a profound sensitivity to platinum-containing regimens.
  
  
  METHODS
  CT scans demonstrated progressing liver, lung and peritoneal metastases and MRI detected multiple intracerebral metastases.
  
  
  METHODS
  New brain metastases secondary to progressive endometrioid endometrial carcinoma.
  
  
  RESULTS
  On the basis of her sensitivity to repeated platinum treatment she was treated with the oral poly(ADP)-ribose polymerase (PARP) 1 inhibitor olaparib as part of a phase I trial. Repeat MRI scan at week 10 of treatment showed a significant reduction in the size of the brain metastases without steroid treatment or radiotherapy and the patient reported subjective improvement in tumor-related symptoms. After 8 months of olaparib treatment the patient developed objective disease progression. The tumor biopsy was negative for somatic BRCA1 and BRCA2 mutations, but displayed loss of PTEN, which has been suggested to be another predictive marker for sensitivity to PARP inhibitors. The patient remained alive for 10 months after completing olaparib, having gone on to derive further clinical benefit from repeat exposure to platinum-based therapy.
authors.affiliation: Drug Development Unit, Royal Marsden Hospital, Institute of Cancer Research, Downs Road, Sutton, Surrey SM2 5PT, UK.
authors.forename: Martin D
authors.initials: MD
authors.lastname: Forster
authors.forename: Konstantin J
authors.initials: KJ
authors.lastname: Dedes
authors.forename: Shahneen
authors.initials: S
authors.lastname: Sandhu
authors.forename: Sophia
authors.initials: S
authors.lastname: Frentzas
authors.forename: Rebecca
authors.initials: R
authors.lastname: Kristeleit
authors.forename: Alan
authors.initials: A
authors.lastname: Ashworth
authors.forename: Christopher J
authors.initials: CJ
authors.lastname: Poole
authors.forename: Britta
authors.initials: B
authors.lastname: Weigelt
authors.forename: Stan B
authors.initials: SB
authors.lastname: Kaye
authors.forename: L Rhoda
authors.initials: LR
authors.lastname: Molife
mesh_terms: D000230:Adenocarcinoma / Q000188:drug therapy / Q000235:genetics / Q000473:pathology; D001932:Brain Neoplasms / Q000188:drug therapy* / Q000235:genetics / Q000556:secondary; D018269:Carcinoma, Endometrioid / Q000188:drug therapy* / Q000235:genetics / Q000473:pathology; D016889:Endometrial Neoplasms / Q000188:drug therapy* / Q000235:genetics / Q000473:pathology; D005260:Female; D006801:Humans; D008113:Liver Neoplasms / Q000188:drug therapy / Q000235:genetics / Q000556:secondary; D008175:Lung Neoplasms / Q000188:drug therapy / Q000235:genetics / Q000556:secondary; D008875:Middle Aged; D009364:Neoplasm Recurrence, Local / Q000188:drug therapy / Q000235:genetics / Q000473:pathology; D051059:PTEN Phosphohydrolase / Q000172:deficiency* / Q000235:genetics; D010534:Peritoneal Neoplasms / Q000188:drug therapy / Q000235:genetics / Q000556:secondary; D010793:Phthalazines / Q000627:therapeutic use*; D010879:Piperazines / Q000627:therapeutic use*; D000067856:Poly(ADP-ribose) Polymerase Inhibitors; D016896:Treatment Outcome
chemical_list: D010793:Phthalazines; D010879:Piperazines; D000067856:Poly(ADP-ribose) Polymerase Inhibitors; D051059:PTEN Phosphohydrolase; C494929:PTEN protein, human; C531550:olaparib