Meta-analysis of the cumulative risk of endometrial malignancy and systematic review of endometrial surveillance in extended tamoxifen therapy

Br J Surg. 2018 Aug;105(9):1098-1106. doi: 10.1002/bjs.10899. Epub 2018 Jul 4.


Background: Optimal management of the endometrium in patients with oestrogen receptor-positive breast cancer taking extended tamoxifen therapy (for 10 years) remains uncertain. A meta-analysis was performed to determine the cumulative risk ratio (RR) for endometrial malignancy following extended compared with standard tamoxifen treatment. A systematic review was undertaken to identify whether routine endometrial surveillance in patients receiving tamoxifen is associated with earlier detection and reduced incidence of endometrial malignancy.

Methods: Two independent searches were undertaken in the Cochrane Library, PubMed and MEDLINE. A meta-analysis was performed of RCTs reporting on endometrial malignancy risk in extended tamoxifen therapy. A systematic review included prospective studies investigating the benefit of endometrial surveillance during tamoxifen therapy.

Results: Four RCTs reported on endometrial risk in extended tamoxifen therapy. The cumulative risk of endometrial malignancy increased twofold from 1·5 to 3·2 per cent with extended therapy compared with the standard 5 years of tamoxifen (RR 2·29, 95 per cent c.i. 1·60 to 3·28; P < 0·001). Four studies analysed the value of endometrial screening in 5-year cohorts. Endometrial cancer rates of up to 2 per cent were reported, which is higher than rates in the large extended tamoxifen trials.

Conclusion: Extended adjuvant tamoxifen is associated with an increase in endometrial cancer. No clear benefit has been shown for routine endometrial surveillance in asymptomatic patients on tamoxifen therapy.

Publication types

  • Meta-Analysis
  • Systematic Review

MeSH terms

  • Antineoplastic Agents, Hormonal / therapeutic use
  • Disease Progression
  • Endometrial Neoplasms / drug therapy*
  • Endometrial Neoplasms / epidemiology
  • Female
  • Global Health
  • Humans
  • Incidence
  • Tamoxifen / therapeutic use*
  • Treatment Outcome


  • Antineoplastic Agents, Hormonal
  • Tamoxifen