Letrozole

• 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.

Pharmacokinetics

• 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).