Anti-Estrogen Therapy Trade Names
The major anti-estrogen agents used in breast cancer treatment include tamoxifen (Nolvadex), the aromatase inhibitors anastrozole (Arimidex), letrozole (Femara), and exemestane (Aromasin), the selective estrogen receptor modulator raloxifene (Evista), and the selective estrogen receptor degrader fulvestrant (Faslodex). 1, 2, 3
Selective Estrogen Receptor Modulators (SERMs)
Tamoxifen (Nolvadex) is the most commonly used SERM for treatment and prevention of breast cancer, functioning as an estrogen antagonist on breast tissue while having estrogen-like effects on bone and lipids. 1, 4
Raloxifene (Evista) is approved for breast cancer risk reduction in postmenopausal women at high risk, with dosing of 60 mg per day orally for 5 years. 1
Toremifene has an antagonist/agonist profile similar to tamoxifen and is used in breast cancer treatment. 4
Clomiphene citrate (Clomid) is primarily used for infertility treatment rather than breast cancer. 4
Third-Generation Aromatase Inhibitors (AIs)
Nonsteroidal Aromatase Inhibitors
Anastrozole (Arimidex) is a nonsteroidal aromatase inhibitor recommended as first-line treatment for postmenopausal women with hormone receptor-positive metastatic breast cancer. 1, 2, 3
Letrozole (Femara) is a nonsteroidal aromatase inhibitor that demonstrated superior time to progression and overall response rate compared to tamoxifen in phase III trials. 1, 2, 3
Steroidal Aromatase Inhibitor
- Exemestane (Aromasin) is an irreversible steroidal aromatase inhibitor that showed superiority to tamoxifen in terms of overall response rate and time to progression, and is approved for breast cancer risk reduction at 25 mg per day orally for 5 years. 1, 2, 3
Selective Estrogen Receptor Degraders (SERDs)
Fulvestrant (Faslodex) is a pure antiestrogen that binds to the estrogen receptor with similar affinity as estradiol and produces loss of ER within the tumor, administered at 500 mg IM monthly with a loading dose on days 1,15, and 29 of the first month. 1, 5, 6
Elacestrant is a newer oral SERD approved in 2023 for ESR1-mutated disease. 5
Ovarian Suppression Agents
- Goserelin and leuprolide (Lupron) are GnRH agonists used for ovarian suppression in premenopausal women, with leuprolide dosed at 3.75 mg subcutaneously every 28 days. 1, 7
Investigational SERMs
- Bazedoxifene (component of Duavee) and lasofoxifene are third-generation SERMs approved in the European Union for postmenopausal osteoporosis and have shown significant reduction in breast cancer risk. 8, 9
Clinical Context for Selection
Aromatase inhibitors (anastrozole, letrozole, exemestane) are recommended as first-line treatment over tamoxifen for postmenopausal patients with hormone receptor-positive metastatic breast cancer based on more favorable toxicity profiles. 1
Fulvestrant plus CDK4/6 inhibitor (palbociclib, ribociclib, or abemaciclib) is the preferred first-line approach for postmenopausal women with HR-positive, HER2-negative metastatic breast cancer based on overall survival benefits. 5
All anti-estrogen regimens in premenopausal women require concurrent ovarian suppression with GnRH agonists (goserelin or leuprolide) to ensure adequate estrogen suppression. 1, 7, 5