What is Anastrazole (Aromatase Inhibitor)?

What is Anastrozole?

Anastrozole is a non-steroidal aromatase inhibitor that significantly reduces estrogen levels in postmenopausal women by inhibiting the aromatase enzyme, which converts androgens to estrogens. 1

Mechanism of Action

Anastrozole works by:

• Selectively inhibiting the aromatase enzyme that converts adrenal androgens (primarily androstenedione and testosterone) to estrone and estradiol 1
• Suppressing serum estradiol concentrations by approximately 70% within 24 hours and by approximately 80% after 14 days of daily dosing 1
• Having no detectable effect on formation of adrenal corticosteroids or aldosterone 1

Clinical Uses

Anastrozole is primarily used in:

1. Adjuvant Treatment:

   • For postmenopausal women with hormone receptor-positive early-stage breast cancer 2
   • Can be used as initial therapy for 5 years or sequentially after 2-3 years of tamoxifen 2

2. Metastatic Breast Cancer:

   • Recommended as first-line treatment for postmenopausal patients with hormone receptor-positive metastatic breast cancer 2
   • Used as second-line therapy following tamoxifen failure 2

Dosage and Administration

• Standard dose: 1 mg orally once daily 1
• Food reduces the rate but not the overall extent of absorption 1
• Pharmacokinetics are linear over the dose range of 1 to 20 mg 1
• Steady-state plasma levels are reached after approximately 7 days of once-daily dosing 1

Advantages Over Tamoxifen

Compared to tamoxifen, anastrozole has:

• Fewer endometrial cancers 2
• Reduced gynecologic complaints 2
• Lower risk of thromboembolic events 2
• Better disease-free survival in postmenopausal women with hormone receptor-positive breast cancer 2

Side Effects and Safety Profile

Common side effects include:

• Gastrointestinal disturbances 3
• Musculoskeletal symptoms (arthralgias) 2
• Bone fractures (increased risk compared to tamoxifen) 2
• Hot flushes 3
• Headache and asthenia 3

Important safety considerations:

• Increased risk of bone loss and osteoporosis 2
• In the ATAC trial, anastrozole was associated with a higher fracture rate (11.0%) compared to tamoxifen (7.7%) 2
• Unlike some other aromatase inhibitors, anastrozole has not shown significant increases in cardiovascular events in long-term follow-up 2

Important Clinical Considerations

1. Patient Selection:

   • Only effective in postmenopausal women 2
   • Not effective in premenopausal women as it does not adequately suppress ovarian estrogen synthesis 2
   • Most beneficial in women with estrogen receptor-positive breast cancer 2

2. Monitoring:

   • Bone mineral density should be monitored due to increased risk of osteoporosis 2
   • Consider calcium and vitamin D supplementation 2

3. Drug Interactions:

   • Minimal drug interactions as it has limited effect on cytochrome P450 enzymes 1

Comparison to Other Aromatase Inhibitors

Anastrozole belongs to the third-generation non-steroidal aromatase inhibitors, along with letrozole, while exemestane is a steroidal inhibitor 2. All three have shown efficacy in breast cancer treatment, but anastrozole has:

• The most extensive long-term safety data 2
• Confirmed superiority to tamoxifen extending over the full 5-year treatment period 2
• Potentially fewer cardiovascular side effects compared to letrozole and exemestane 2

Anastrozole represents an important advancement in the treatment of hormone-sensitive breast cancer in postmenopausal women, offering improved efficacy and a different side effect profile compared to earlier hormonal therapies.