Treatment with olaparib in a patient with PTEN-deficient endometrioid endometrial cancer

Nat Rev Clin Oncol. 2011 May;8(5):302-6. doi: 10.1038/nrclinonc.2011.42. Epub 2011 Apr 5.


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.

Investigation: CT scans demonstrated progressing liver, lung and peritoneal metastases and MRI detected multiple intracerebral metastases.

Diagnosis: New brain metastases secondary to progressive endometrioid endometrial carcinoma.

Management: 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.

Publication types

  • Case Reports
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adenocarcinoma / drug therapy
  • Adenocarcinoma / genetics
  • Adenocarcinoma / pathology
  • Brain Neoplasms / drug therapy*
  • Brain Neoplasms / genetics
  • Brain Neoplasms / secondary
  • Carcinoma, Endometrioid / drug therapy*
  • Carcinoma, Endometrioid / genetics
  • Carcinoma, Endometrioid / pathology
  • Endometrial Neoplasms / drug therapy*
  • Endometrial Neoplasms / genetics
  • Endometrial Neoplasms / pathology
  • Female
  • Humans
  • Liver Neoplasms / drug therapy
  • Liver Neoplasms / genetics
  • Liver Neoplasms / secondary
  • Lung Neoplasms / drug therapy
  • Lung Neoplasms / genetics
  • Lung Neoplasms / secondary
  • Middle Aged
  • Neoplasm Recurrence, Local / drug therapy
  • Neoplasm Recurrence, Local / genetics
  • Neoplasm Recurrence, Local / pathology
  • PTEN Phosphohydrolase / deficiency*
  • PTEN Phosphohydrolase / genetics
  • Peritoneal Neoplasms / drug therapy
  • Peritoneal Neoplasms / genetics
  • Peritoneal Neoplasms / secondary
  • Phthalazines / therapeutic use*
  • Piperazines / therapeutic use*
  • Poly(ADP-ribose) Polymerase Inhibitors*
  • Treatment Outcome


  • Phthalazines
  • Piperazines
  • Poly(ADP-ribose) Polymerase Inhibitors
  • PTEN Phosphohydrolase
  • PTEN protein, human
  • olaparib