Recommended Dose of Letrozole for Hormone Receptor-Positive Breast Cancer in Postmenopausal Women
The standard recommended dose of letrozole for postmenopausal women with hormone receptor-positive breast cancer is 2.5 mg once daily, taken orally without regard to meals. 1
Dosing Recommendations by Treatment Setting
Adjuvant Treatment
- Dose: 2.5 mg once daily
- Duration: Optimal duration is 5 years, though the exact duration may vary based on clinical context 2
- Administration: Can be taken without regard to meals 1
Extended Adjuvant Treatment
- Dose: 2.5 mg once daily
- Duration: 5 years after completion of 5 years of tamoxifen therapy
- Evidence: Median treatment duration in clinical trials was 60 months, with 71% of patients treated for at least 3 years 1
Advanced/Metastatic Breast Cancer
- Dose: 2.5 mg once daily
- Duration: Continue until tumor progression is evident 1
- First-line option: Preferred over tamoxifen based on superior time to progression (9.4 vs 6.0 months) 3
Special Populations
Hepatic Impairment
- Mild to moderate impairment: No dose adjustment needed
- Severe hepatic dysfunction or cirrhosis: Reduce dose by 50% (2.5 mg every other day) 1
Renal Impairment
- Creatinine clearance ≥10 mL/min: No dose adjustment required 1
Monitoring and Side Effect Management
Bone Health
- Risk: Letrozole causes decreases in bone mineral density
- Monitoring: Consider baseline and periodic bone mineral density testing
- Prevention: Calcium and vitamin D supplementation recommended 4
- Data: At 24 months, median decrease in lumbar spine BMD of 4.1% with letrozole compared to a median increase of 0.3% with tamoxifen 2
Common Side Effects
- Musculoskeletal: Arthralgia (53%), myalgia (28%), arthritis (33%) 2
- Vasomotor: Hot flashes (38%), fatigue (36%) 2
- Cardiovascular: Monitor for cardiovascular events (12%) 2
- Bone: New osteoporosis (11%), bone fractures (14%) 2
Alternative Dosing Considerations
For patients experiencing significant side effects, alternative dosing regimens may be considered, though these are not FDA-approved:
- Research has shown that lower, intermittent doses (e.g., 2.5 mg Monday/Wednesday/Friday) can achieve effective estrogen suppression (75-78% reduction in serum estradiol) 5
- However, these alternative dosing regimens did not show significant differences in side effect profiles compared to standard dosing 5
Comparative Efficacy with Other Aromatase Inhibitors
- Letrozole (2.5 mg daily) and anastrozole (1 mg daily) showed similar 5-year disease-free survival rates (84.9% vs 82.9%) and overall survival rates (89.9% vs 89.2%) in the FACE trial 6
- Side effect profiles were comparable between letrozole and anastrozole 6
Important Considerations
- Contraindications: Pregnancy and known hypersensitivity to letrozole 1
- Pregnancy warning: Can cause fetal harm; advise patients of reproductive potential to use effective contraception 1
- Discontinuation: Treatment should be discontinued at tumor relapse 1
The evidence strongly supports the 2.5 mg once-daily dose as the standard for letrozole across all treatment settings for postmenopausal women with hormone receptor-positive breast cancer, with appropriate dose modifications for patients with severe hepatic impairment.