What are the commonly used aromatase inhibitors (AIs) for hormone receptor-positive breast cancer in postmenopausal women?

Commonly Used Aromatase Inhibitors for Hormone Receptor-Positive Breast Cancer

The three commonly used aromatase inhibitors (AIs) for hormone receptor-positive breast cancer in postmenopausal women are anastrozole, letrozole, and exemestane. 1

Classification of Aromatase Inhibitors

Aromatase inhibitors are classified into two main categories:

1. Non-steroidal (reversible) aromatase inhibitors:

   • Anastrozole (Arimidex)
   • Letrozole (Femara)

2. Steroidal (irreversible) aromatase inhibitor:

   • Exemestane (Aromasin)

Mechanism of Action

Aromatase inhibitors work by blocking the enzyme aromatase, which converts androgens to estrogens in postmenopausal women. This leads to a significant reduction in circulating estrogen levels, which is beneficial in hormone receptor-positive breast cancer where tumor growth is stimulated by estrogen.

FDA-Approved Indications

• Letrozole:

  • Adjuvant treatment of postmenopausal women with hormone receptor-positive early breast cancer
  • Extended adjuvant treatment after standard adjuvant tamoxifen therapy
  • First and second-line treatment of advanced breast cancer 2

• Exemestane:

  • Adjuvant treatment after 2-3 years of tamoxifen (switch therapy)
  • Treatment of advanced breast cancer after tamoxifen failure 3

• Anastrozole:

  • Adjuvant treatment of postmenopausal women with hormone receptor-positive early breast cancer
  • First-line treatment for advanced breast cancer 1

Clinical Use in Breast Cancer Treatment

Aromatase inhibitors can be used in several treatment strategies:

1. Primary (initial) therapy: Using an AI alone for 5 years 1
2. Sequential therapy: Using tamoxifen for 2-3 years followed by an AI (or vice versa) to complete 5 years of treatment 1
3. Extended therapy: Using an AI after completing 5 years of tamoxifen 1

Comparative Efficacy

• All three third-generation AIs have demonstrated superiority over tamoxifen or are at least equivalent in terms of disease-free survival 4, 5
• Letrozole has shown significant superiority to tamoxifen in first-line treatment regarding time to progression and response rate 4
• There is some evidence of incomplete cross-resistance between steroidal (exemestane) and non-steroidal (anastrozole, letrozole) AIs, allowing for sequential use 1

Side Effect Profiles

Aromatase inhibitors have a different side effect profile compared to tamoxifen:

• Lower risk of:

  • Endometrial cancer
  • Thromboembolic events
  • Gynecologic symptoms
  • Vaginal bleeding 1

• Higher risk of:

  • Bone fractures and osteoporosis
  • Musculoskeletal symptoms (arthralgia, myalgia)
  • Joint pain 1, 6
  • Cardiovascular events (though the true impact remains to be fully clarified) 6

Important Clinical Considerations

• AIs are only effective in postmenopausal women and should not be used in women with functioning ovaries 1
• Ovarian function cannot be reliably assessed in women with treatment-induced amenorrhea 1
• Bone mineral density monitoring is recommended during AI treatment due to increased risk of osteoporosis 6, 7
• Lipid profile monitoring may be advisable due to potential effects on cardiovascular risk 6

Conclusion

The third-generation aromatase inhibitors—anastrozole, letrozole, and exemestane—are essential medications in the treatment of hormone receptor-positive breast cancer in postmenopausal women, offering improved disease-free survival compared to tamoxifen alone. The choice between these agents should consider their specific indications, side effect profiles, and the individual patient's clinical situation.