Can a woman who has taken letrozole (an aromatase inhibitor) at 5mg a day for 5 days for the last four cycles stop for one or two months and restart, or is it recommended to taper the dose before taking a break?

Intermittent Letrozole Therapy: Safety and Efficacy

Yes, a woman who has taken letrozole at 5mg daily for 5 days for four cycles can safely stop for one or two months and restart without tapering the dose. Based on clinical evidence, intermittent letrozole therapy is both safe and effective, with potential quality of life benefits compared to continuous use.

Evidence for Intermittent Letrozole Use

• The SOLE trial (Study of Letrozole Extension) specifically evaluated intermittent versus continuous letrozole therapy and found that intermittent administration was non-inferior to continuous therapy in terms of disease-free survival (HR, 1.08; 95% CI, 0.93 to 1.26; P = .31) 1
• Intermittent letrozole administration (using a schedule of 9 months on, 3 months off) showed comparable efficacy to continuous administration while providing quality of life benefits 1
• At 24 months, patients on intermittent letrozole showed greater improvement in hot flushes (P = .025) compared to those on continuous therapy 1

Benefits of Intermittent Therapy

• Patients on intermittent letrozole reported significantly less vaginal problems (P = .017), improved sleep (P = .0073), better physical well-being (P = .0080), and improved mood (P = .026) compared to continuous administration 1
• Taking breaks from letrozole may reduce cumulative side effects while maintaining therapeutic efficacy 1
• No evidence suggests that brief interruptions in letrozole therapy compromise long-term outcomes when the medication is restarted 1

Considerations When Stopping and Restarting

• No tapering is required when stopping letrozole at 5mg daily for 5 days per cycle 1, 2
• The standard protocol for letrozole in fertility treatment is typically 5 days of therapy per cycle, which already incorporates natural breaks between cycles 2
• When restarting after a 1-2 month break, the same dosage (5mg daily for 5 days) can be resumed without modification 2

Monitoring Recommendations

• Upon restarting letrozole after a break, monitor for common side effects including hot flashes, fatigue, arthralgia, and myalgia 1
• Long-term letrozole use is associated with increased risk of osteoporosis and bone fractures, but these risks are unlikely to be significantly affected by a 1-2 month break 1, 2
• Regular assessment of bone mineral density is recommended for patients on extended letrozole therapy, particularly if planning to continue treatment long-term 2

Conclusion for Clinical Practice

• For a woman who has taken letrozole at 5mg daily for 5 days for four cycles, a 1-2 month break followed by resumption at the same dose is appropriate and does not require tapering 1, 2
• This approach may provide quality of life benefits while maintaining therapeutic efficacy 1
• Upon resuming therapy, the standard dose of 5mg daily for 5 days can be continued 2