Overview
Letrozole is a nonsteroidal aromatase inhibitor used primarily in the treatment of hormone receptor-positive breast cancer in postmenopausal women. It works by inhibiting the conversion of androgens to estrogens, thereby reducing estrogen levels that can stimulate cancer growth.
Mechanism of Action
Letrozole is a nonsteroidal competitive inhibitor of the aromatase enzyme system, which converts androgens (androstenedione and testosterone) to estrogens (estrone and estradiol). By binding reversibly to the heme group of aromatase, it inhibits estrogen synthesis in peripheral tissues and cancer cells, leading to reduced estrogen levels.
Indications
- Adjuvant treatment of postmenopausal women with hormone receptor-positive early breast cancer
- Extended adjuvant treatment of postmenopausal women with early breast cancer who have received prior standard adjuvant tamoxifen therapy
- First-line treatment of postmenopausal women with hormone receptor-positive or hormone receptor unknown locally advanced or metastatic breast cancer
- Treatment of advanced breast cancer in postmenopausal women with disease progression following antiestrogen therapy
Dosage
2.5 mg orally once daily, with or without food. Treatment duration varies based on indication: adjuvant treatment typically for 5 years, extended adjuvant for up to 5 years after tamoxifen, and advanced/metastatic treatment until disease progression.
Contraindications
- Pregnancy
- Pre-menopausal women
- Women of childbearing potential not using effective contraception
- Hypersensitivity to letrozole or any component of the formulation
Side Effects
- Hot flashes
- Arthralgia
- Fatigue
- Headache
- Nausea
- Back pain
- Dyspnea
- Cough
- Constipation
- Diarrhea
- Increased sweating
- Hypertension
- Peripheral edema
- Bone pain
- Insomnia
- Dizziness
- Weight gain
- Hypercholesterolemia
Interactions
- Tamoxifen: Concurrent use may reduce letrozole plasma concentrations
- Estrogen-containing therapies: May diminish therapeutic effect of letrozole
- CYP2A6 and CYP3A4 inducers: May decrease letrozole concentrations
- CYP2A6 and CYP3A4 inhibitors: May increase letrozole concentrations