- Class: Aromatase inhibitor (non-steroidal)
- Mechanism of Action: Letrozole inhibits aromatase enzyme, which converts androgens to estrogens in peripheral tissues. This lowers estrogen levels, reducing estrogen stimulation of hormone receptor–positive breast cancer cells.
Indications
- Hormone receptor–positive (ER+ and/or PR+), postmenopausal breast cancer:
- Early-stage breast cancer as adjuvant therapy.
- Advanced or metastatic breast cancer.
- Used in combination with CDK4/6 inhibitors (e.g., ribociclib, palbociclib).
- Sometimes used off-label for ovarian stimulation or fertility treatment.
Dosage
- Standard dose: 2.5 mg orally once daily, with or without food.
- Absorption: Rapid oral absorption.
- Metabolism: Hepatic via CYP3A4 and CYP2A6.
- Half-life: ~2 days (40–60 hours).
- Elimination: Mainly urinary.
Key Toxicities and Monitoring
- Common adverse effects:
- Hot flashes
- Arthralgia/myalgia
- Fatigue
- Osteoporosis (due to estrogen depletion)
- Less common: Elevated cholesterol, liver enzyme elevations.
- Monitoring:
- Bone density (DEXA scan) periodically during long-term use.
- Lipid profile.
- Liver function tests if indicated.
Drug Interactions
- Caution with drugs affecting CYP3A4; however, clinically significant interactions are uncommon.
- May increase plasma concentrations of tamoxifen (use avoided in combination).