Long-term endometrial effects in postmenopausal women with early breast cancer participating in the Intergroup Exemestane Study (IES)--a randomised controlled trial of exemestane versus continued tamoxifen after 2-3 years tamoxifen

Ann Oncol. 2010 Mar;21(3):498-505. doi: 10.1093/annonc/mdp358. Epub 2009 Aug 28.


Background: The antiestrogen tamoxifen may have partial estrogen-like effects on the postmenopausal uterus. Aromatase inhibitors (AIs) are increasingly used after initial tamoxifen in the adjuvant treatment of postmenopausal early breast cancer due to their mechanism of action: a potential benefit being a reduction of uterine abnormalities caused by tamoxifen.

Patients and methods: Sonographic uterine effects of the steroidal AI exemestane were studied in 219 women participating in the Intergroup Exemestane Study: a large trial in postmenopausal women with estrogen receptor-positive (or unknown) early breast cancer, disease free after 2-3 years of tamoxifen, randomly assigned to continue tamoxifen or switch to exemestane to complete 5 years adjuvant treatment. The primary end point was the proportion of patients with abnormal (> or =5 mm) endometrial thickness (ET) on transvaginal ultrasound 24 months after randomisation.

Results: The analysis included 183 patients. Two years after randomisation, the proportion of patients with abnormal ET was significantly lower in the exemestane compared with tamoxifen arm (36% versus 62%, respectively; P = 0.004). This difference emerged within 6 months of switching treatment (43.5% versus 65.2%, respectively; P = 0.01) and disappeared within 12 months of treatment completion (30.8% versus 34.7%, respectively; P = 0.67).

Conclusion: Switching from tamoxifen to exemestane significantly reverses endometrial thickening associated with continued tamoxifen.

Publication types

  • Clinical Trial, Phase III
  • Comparative Study
  • Multicenter Study
  • Randomized Controlled Trial
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Aged
  • Androstadienes / therapeutic use*
  • Antineoplastic Agents, Hormonal / therapeutic use*
  • Aromatase Inhibitors / therapeutic use*
  • Breast Neoplasms / drug therapy*
  • Breast Neoplasms / pathology
  • Carcinoma, Ductal, Breast / drug therapy
  • Carcinoma, Ductal, Breast / pathology
  • Carcinoma, Lobular / drug therapy
  • Carcinoma, Lobular / pathology
  • Double-Blind Method
  • Endometrial Neoplasms / diagnostic imaging
  • Endometrial Neoplasms / drug therapy
  • Endometrial Neoplasms / pathology*
  • Female
  • Follow-Up Studies
  • Humans
  • International Agencies
  • Middle Aged
  • Postmenopause
  • Survival Rate
  • Tamoxifen / therapeutic use*
  • Time Factors
  • Treatment Outcome
  • Ultrasonography


  • Androstadienes
  • Antineoplastic Agents, Hormonal
  • Aromatase Inhibitors
  • Tamoxifen
  • exemestane