Raloxifene and Tamoxifen

Summary

In breast tissue, both tamoxifen and raloxifene act as antagonists. This makes these drugs useful in the treatment of Estrogen-responsive breast cancers. In bone, both tamoxifen and raloxifene act as partial agonists. This makes both drugs useful in preventing osteoporosis. Crucially, tamoxifen and raloxifene have opposite effects in endometrial tissue. Tamoxifen is a partial agonist, which also means that it comes with an increased risk of endometrial hyperplasia and carcinoma. However, raloxifene is an antagonist in endometrial tissue, so it does not increase the risk of endometrial cancer.  Finally, both tamoxifen and raloxifene can cause thromboembolic events and hot flashes. 

Key Points

• Raloxifene, Tamoxifen
  • Mechanism
    • Selective estrogen receptor modulator (SERM)
      • Agonist OR Antagonist activity at estrogen receptor depending on tissue
        • In breast: tamoxifen/raloxifen antagonizes (good in ER+ or PR+ BrCa)
        • In bone: tamoxifen/raloxifen is a partial agonist (good vs. osteoporosis)
        • In endometrium: tamoxifen is partial agonist (hence endometrial hyperplasia/cancer risk), but raloxifen is NOT
  • Clinical use
    • Breast cancer treatment/prevention
    • Prevention of osteoporosis
  • Adverse effects
    • Tamoxifen increases risk of endometrial cancer (ER partial agonist), but raloxifene does NOT (ER antagonist)
      • Raloxifene - no increased risk so “you can relax”
    • Increased risk of thromboembolic events (DVT, PE)
    • Hot flashes
      • This should make sense, because the drugs are modulating hormone receptors, right?