Aromatase inhibitors alone or sequentially combined with tamoxifen in postmenopausal early breast cancer compared with tamoxifen or placebo - Meta-analyses on efficacy and adverse events based on randomized clinical trials

Breast. 2016 Apr;26:106-14. doi: 10.1016/j.breast.2016.01.006. Epub 2016 Feb 18.


Tamoxifen (TAM) and aromatase inhibitors (AI) are adjuvant therapy options for postmenopausal women with estrogen receptor positive (ER+) breast cancer. This systematic review of seven randomized controlled studies comparing TAM and AI, and one study comparing extended therapy with an AI with placebo after about 5 years of tamoxifen, aims to assess long-term clinical efficacy and adverse events. The literature review was performed according to the principles of the Cochrane Collaboration. The search included common databases up to 2013-01-14. Studies of high or moderate quality were used for grading of evidence. Revman™ software was utilized for meta-analyses of published data. Disease free survival (DFS) and overall survival (OS) were improved with AI monotherapy compared to TAM with high and moderate quality of evidence respectively. Sequenced therapy with AI → TAM (or vice versa) improved DFS compared with TAM with moderate quality of evidence, but did not improve OS (low quality of evidence). However, if only studies on sequenced AI therapy with randomization before endocrine therapy were considered, no improvement of DFS could be found. Fractures are more frequently associated with AI whereas the risk of endometrial cancer and venous thromboembolism are higher with TAM. For cardiovascular events no difference was found between AI (mono- or sequenced therapy) and TAM, whereas sequenced therapy compared with AI had lower risk of cardiovascular events (moderate level of evidence). AIs are superior to TAM as adjuvant hormonal therapy for postmenopausal ER-positive breast cancer. TAM can be considered for individual patients due to the different toxicity profile compared with AI. Cardiovascular events related to AI treatment deserve further attention.

Keywords: Adverse events; Aromatase inhibitors; Early breast cancer; Randomized clinical trial; Systematic review; Tamoxifen.

Publication types

  • Meta-Analysis
  • Research Support, Non-U.S. Gov't
  • Review
  • Systematic Review

MeSH terms

  • Aged
  • Antineoplastic Agents / administration & dosage*
  • Antineoplastic Agents / adverse effects
  • Antineoplastic Combined Chemotherapy Protocols / administration & dosage
  • Antineoplastic Combined Chemotherapy Protocols / adverse effects
  • Aromatase Inhibitors / administration & dosage*
  • Aromatase Inhibitors / adverse effects
  • Breast Neoplasms / drug therapy*
  • Breast Neoplasms / pathology
  • Cardiovascular Diseases / chemically induced
  • Female
  • Humans
  • Middle Aged
  • Postmenopause*
  • Randomized Controlled Trials as Topic
  • Tamoxifen / administration & dosage*
  • Tamoxifen / adverse effects
  • Treatment Outcome


  • Antineoplastic Agents
  • Aromatase Inhibitors
  • Tamoxifen