Selective Estrogen Receptor Modulator (SERM)

• Examples of SERM include tamoxifen, raloxifene
• Tamoxifen is the first line therapy for ER-positive breast cancer
• Why tamoxifen is classified as selective ER modulator?

  Because it has weak estrogenic activity in other tissue but PRO-estrogenic activity in uterus
• Tamoxifen has pro-estrogenic activity in uterus, what is the ADR?

  Increase risk of uterine cancer in breast cancer patient treated with Tamoxifen
• MOA of Tamoxifen:

  1. binds to ER
  2. producing an inactive complex
  3. this complex fails to induce estrogen-responsive genes
  4. RNA synthesis does not happen
  5. Depletion of ER
  6. Growth-promoting effects of natural hormone are suppressed
• What is the major SE of SERM ?

  Thromboembolism
• SE of SERM include hot flashes, N&V, skin rash, vaginal bleeding and discharge, osteoporosis, hypercalcemia, thromboembolism
• Example of aromatase inhibitors can be classified into steroidal inhibitors and non-steroidal inhibitors.

  Steroidal inhibitor -> exemestane

  Non-steroidal inhibitors -> anastrozole, letrozole
• Aromatase inhibitors prevent the formation of estrogen from androgens.
• Estrogen is derived from androgen precursors through the action of enzyme aromatase.
• Aromatase inhibitors is considered as an option in postmenopausal women with ER positive breast cancer. (or) as an adjuvant therapy.
• Several clinical trials have show aromatase inhibitors (AI) to be superior to Tamoxifen as adjuvant therapy in post-menopausal women.

  • improved relapse-free survival
  • reduced the risk of thromboembolic disease and endometrial cancer