Definition & Mechanism
- AIs block the enzyme aromatase, which converts androgens (androstenedione, testosterone) into estrogens (estrone, estradiol) in peripheral tissues (adipose, muscle, liver, breast).
- In postmenopausal women, peripheral aromatization is the primary source of estrogen (ovaries no longer produce significant estrogen).
- Lowering estrogen → suppresses estrogen-dependent tumor growth in ER+ breast cancer.
Types
- Non-steroidal (reversible) inhibitors
- Anastrozole (Arimidex)
- Letrozole (Femara)
- Reversibly bind to aromatase enzyme’s heme group.
- Steroidal (irreversible) inhibitor
- Exemestane (Aromasin)
- Structurally similar to androstenedione, binds irreversibly (“suicide inhibition”).
Oncology Indications
- First-line adjuvant therapy for postmenopausal ER+/PR+ breast cancer.
- Extended adjuvant therapy after tamoxifen.
- Advanced/metastatic ER+ breast cancer in postmenopausal patients.
- Ovarian suppression combination in premenopausal patients (e.g., with goserelin).
Dosing (Adults)
| Drug | Typical Dose | Notes |
|---|---|---|
| Anastrozole | 1 mg PO daily | Food doesn’t affect absorption |
| Letrozole | 2.5 mg PO daily | May be taken with or without food |
| Exemestane | 25 mg PO daily | Take after a meal to ↑ absorption |
- Metabolism: Hepatic (CYP3A4, CYP2A6 for exemestane; CYP3A4, CYP2D6 for anastrozole/letrozole).
- Excretion: Mainly urine/feces.
- Half-life: Anastrozole ~50 hr, Letrozole ~48 hr, Exemestane ~24 hr.
Key Clinical Considerations
- Only effective in postmenopausal estrogen physiology — in premenopausal women, must combine with ovarian suppression.
- Reduces recurrence risk more than tamoxifen in postmenopausal women, but higher bone loss risk.
- Monitor bone mineral density before and during therapy.
- Lipid profile changes possible — monitor cholesterol.
Adverse Effects
- Musculoskeletal: Arthralgia, myalgia, joint stiffness.
- Bone: Osteopenia, osteoporosis, fractures.
- Vasomotor: Hot flashes, night sweats.
- Other: Fatigue, mild nausea, vaginal dryness, headache, hypertension.
Monitoring
- Baseline & periodic bone mineral density (DEXA scan).
- Vitamin D & calcium status.
- Lipid panel periodically.
- Tumor markers & clinical breast exam per oncology protocol.
Drug Interactions
- CYP3A4 inducers (e.g., rifampin, phenytoin) may ↓ AI levels.
- Exemestane: caution with strong CYP3A4 inhibitors (↑ levels).
- Tamoxifen should not be co-administered with AIs in adjuvant setting — antagonistic effect.