Letrozole for Hormone Receptor-Positive Breast Cancer Treatment
Letrozole is recommended at a standard dose of 2.5 mg once daily for postmenopausal women with hormone receptor-positive breast cancer in multiple treatment settings, including adjuvant therapy, extended adjuvant therapy after tamoxifen, and first/second-line treatment for metastatic disease. 1, 2
Approved Indications and Dosing
Letrozole is an aromatase inhibitor with the following approved indications:
Adjuvant treatment: 2.5 mg once daily for postmenopausal women with hormone receptor-positive early breast cancer 1
- Optimal duration is 5 years based on clinical trials 2
Extended adjuvant treatment: 2.5 mg once daily for postmenopausal women who have completed 5 years of tamoxifen therapy 1
- Treatment typically continues for 5 years (median treatment duration in MA-17R trial was 60 months) 2
First-line treatment: 2.5 mg once daily for postmenopausal women with hormone receptor-positive or unknown locally advanced/metastatic breast cancer 1, 2
Second-line treatment: 2.5 mg once daily for postmenopausal women with advanced breast cancer after progression on antiestrogen therapy 1, 2
Efficacy
Letrozole demonstrates superior efficacy compared to tamoxifen in several key areas:
- First-line metastatic setting: Significantly longer time to progression (9.4 vs 6.0 months) 3
- Extended adjuvant setting: 43% relative reduction in disease recurrences compared to placebo 3
- Adjuvant setting: Significant improvement in disease-free survival compared to tamoxifen 4
Special Dosing Considerations
Hepatic impairment:
- Mild to moderate impairment: No dose adjustment needed
- Severe impairment or cirrhosis: Reduce dose to 2.5 mg every other day 1
Renal impairment: No dose adjustment required if creatinine clearance ≥10 mL/min 1
Administration: Can be taken without regard to meals 1
Duration of Treatment
- Adjuvant setting: Optimal duration is 5 years 1
- Extended adjuvant setting: 5 years after completion of tamoxifen 2
- Metastatic setting: Continue until disease progression 1, 2
Monitoring During Treatment
- Bone health: Monitor bone mineral density due to increased risk of osteoporosis and fractures (median decrease in lumbar spine BMD of 4.1% at 24 months) 1, 5
- Lipid profile: Consider monitoring cholesterol levels 1
Common Side Effects
- Hot flashes, arthralgia, myalgia, fatigue, and headache 1, 3
- Lower incidence of thromboembolic events, vaginal bleeding, and gynecologic symptoms compared to tamoxifen 5, 4
- Higher incidence of musculoskeletal issues and bone fractures compared to tamoxifen 5, 4
Contraindications
- Pregnancy (can cause fetal harm) 1
- Premenopausal status 5
- Known hypersensitivity to letrozole or excipients 1
Clinical Pearls
- Verify postmenopausal status before initiating letrozole 5
- Consider bone-protective strategies in women at high risk for fractures 5
- Letrozole should not be combined with chemotherapy 2
- In premenopausal women, if aromatase inhibitors are considered, they must be given with ovarian function suppression 2
- Alternative dosing regimens (such as intermittent dosing) have been studied but are not currently recommended in standard practice 6
Letrozole remains a cornerstone in the treatment of hormone receptor-positive breast cancer, with proven benefits in improving disease-free survival and reducing recurrence risk across multiple treatment settings.