Is it necessary to stop Femara (letrozole) after 10 years?

Should You Stop Femara After 10 Years?

Yes, you should stop Femara (letrozole) after 10 years of total endocrine therapy, as extending treatment beyond this duration is not supported by evidence and increases bone-related adverse effects without improving overall survival. 1

Maximum Duration Recommendation

• Women who receive extended adjuvant endocrine therapy should receive no more than 10 years of total treatment. 1
• The ASCO guidelines explicitly state this as a firm recommendation based on available evidence from multiple trials. 1
• The NCCN guidelines align with this position, noting that no data support aromatase inhibitor use beyond 10 years total. 1

Evidence Supporting the 10-Year Limit

The MA.17R trial, which specifically evaluated extending letrozole from 5 to 10 years, provides the key evidence:

• Disease-free survival improved with extended therapy (95% vs 91% at 5 years), but no overall survival benefit was demonstrated. 1, 2
• Contralateral breast cancer rates were lower with extended letrozole (0.21% vs 0.49% annually). 1, 2
• Bone-related adverse effects increased significantly: bone pain (18% vs 14%), fractures (14% vs 9%), and new-onset osteoporosis (11% vs 6%). 1, 2

The AERAS trial with anastrozole showed similar patterns—improved disease-free survival but no overall survival benefit, with increased bone and menopausal adverse events. 3

Why Stop at 10 Years?

The risk-benefit ratio becomes unfavorable beyond 10 years:

• No trials have evaluated aromatase inhibitors beyond 10 years, so safety and efficacy are unknown. 1
• The absolute benefit in disease-free survival is modest (4% difference at 5 years in MA.17R). 1, 2
• Bone health deteriorates progressively with continued therapy, increasing fracture risk. 1, 2
• Quality of life considerations favor stopping, as menopausal symptoms and musculoskeletal complaints persist. 1

Critical Caveats

Before stopping, ensure appropriate bone health management:

• Obtain final bone density assessment to determine if bone-directed therapy (bisphosphonates or denosumab) should continue after stopping letrozole. 4
• Continue calcium and vitamin D supplementation indefinitely. 4
• Monitor for late recurrence risk, which persists years 5-20 after diagnosis, though this doesn't justify indefinite therapy. 1

The decision applies regardless of risk level:

• Even high-risk patients (≥4 positive lymph nodes) should not exceed 10 years total endocrine therapy. 1
• The lack of overall survival benefit holds across all risk subgroups studied. 1, 2