Should a patient continue taking exemestane (aromatase inhibitor) for breast cancer management?

Exemestane Continuation in Breast Cancer Management

Exemestane should be continued for a total of 5 years of endocrine therapy in postmenopausal women with hormone receptor-positive breast cancer to reduce the risk of recurrence and improve disease-free survival. 1

Efficacy of Exemestane in Breast Cancer Treatment

Exemestane is an irreversible steroidal aromatase inhibitor that effectively suppresses aromatase activity and circulating estrogen levels in postmenopausal women. Clinical evidence supports its continued use for several reasons:

• The Intergroup Exemestane Study (IES) demonstrated that switching to exemestane after 2-3 years of tamoxifen therapy significantly improved disease-free survival compared to continuing tamoxifen (HR, 0.76; 95% CI, 0.66–0.88; P=0.0001) 1
• Exemestane showed a significant difference in overall survival in patients with ER-positive tumors (HR, 0.83; 95% CI, 0.69–1.00; log rank P=0.05) 1
• The NCCN guidelines support completing a total of 5 years of endocrine therapy, with exemestane being an effective option 1

Comparison with Other Aromatase Inhibitors

According to the 2024 NCCN guidelines, there are no meaningful differences in efficacy or toxicity between the available aromatase inhibitors (exemestane, anastrozole, and letrozole) 1. All three have shown similar antitumor efficacy and toxicity profiles in randomized studies in the adjuvant setting.

Managing Side Effects

Common side effects of exemestane that may impact continuation include:

1. Musculoskeletal symptoms:

   • Joint stiffness and arthralgias
   • Consider calcium and vitamin D supplementation 2
   • Monitor bone mineral density as exemestane can cause bone loss 3

2. Vasomotor symptoms:

   • Hot flashes and increased sweating 3
   • These symptoms typically reflect the estrogen-suppressive effects of the drug

3. Other common side effects:

   • Fatigue, nausea, and dizziness 3
   • Dry eyes and vaginal dryness 2

Algorithm for Decision-Making

1. Assess treatment duration to date:

   • If patient has not completed 5 years of total endocrine therapy, continuation is recommended 1
   • If patient has completed 5 years, consider individual risk factors for recurrence

2. Evaluate tolerability:

   • If side effects are manageable with supportive care, continue treatment
   • For severe side effects, consider:
     • Dose modification
     • Switching to an alternative aromatase inhibitor (letrozole or anastrozole) 2
     • Switching to tamoxifen if aromatase inhibitors are not tolerated 2

3. Assess bone health:

   • Monitor bone mineral density
   • Supplement with calcium and vitamin D
   • Consider bisphosphonate therapy for patients with additional risk factors for bone loss 2

Special Considerations

• For patients with visceral metastases, exemestane maintains its efficacy 4
• Exemestane does not show cross-resistance with nonsteroidal aromatase inhibitors, making it a valuable option in sequential therapy 5
• In advanced disease, exemestane has shown equivalent efficacy to megestrol in patients with disease refractory to tamoxifen 6

Conclusion

When evaluating whether to continue exemestane therapy, the primary consideration should be completing the full 5-year course of endocrine therapy to maximize disease-free survival benefits. Side effects should be managed proactively rather than discontinuing therapy prematurely. If side effects are severe and unmanageable, switching to an alternative aromatase inhibitor or tamoxifen is preferable to discontinuing endocrine therapy altogether.