anastrozole
Summary
Anastrozole is a third-generation nonsteroidal aromatase inhibitor used in the treatment of hormone receptor-positive breast cancer in postmenopausal women. It works by blocking peripheral conversion of androgens to estrogens, reducing estrogen levels. It is a key adjuvant therapy option, often preferred over tamoxifen in postmenopausal patients due to a different side effect profile.
Detail
Anastrozole reversibly inhibits aromatase (CYP19A1), the enzyme responsible for converting androstenedione and testosterone into estrone and estradiol in peripheral tissues (adipose tissue, muscle) and breast tissue. Since postmenopausal women rely on peripheral aromatization (rather than ovarian production) for estrogen synthesis, aromatase inhibitors are effective only in this population; they are ineffective in premenopausal women unless combined with ovarian suppression, because the pituitary-gonadal axis would otherwise upregulate ovarian estrogen production via loss of negative feedback.
Clinical use: Anastrozole is used as adjuvant therapy for hormone receptor-positive (ER+/PR+) early breast cancer in postmenopausal women, often given for 5 years, sometimes in sequence with tamoxifen. It is also used in metastatic breast cancer.
Mechanism comparison: Unlike tamoxifen (a selective estrogen receptor modulator that acts as an estrogen antagonist in breast tissue but agonist in endometrium/bone), anastrozole lowers total body estrogen levels. This leads to a different adverse effect profile: - Increased risk of osteoporosis and bone fractures (unopposed estrogen deficiency effects on bone) - bone density monitoring required. - Arthralgias/myalgias (common reason for discontinuation). - Hot flashes, vaginal dryness. - Increased cardiovascular risk (lipid profile changes) compared to tamoxifen. - Unlike tamoxifen, anastrozole does NOT increase risk of endometrial cancer or venous thromboembolism, making it preferred in patients with these risk factors.
Key boards teaching points: Aromatase inhibitors (anastrozole, letrozole, exemestane) are for postmenopausal women only; tamoxifen/raloxifene (SERMs) can be used in premenopausal or postmenopausal women. Exemestane is a steroidal, irreversible inhibitor, whereas anastrozole and letrozole are nonsteroidal, reversible inhibitors.
Sources
- Katzung's Basic and Clinical Pharmacology
- USMLE First Aid Step 1
- Goodman & Gilman's The Pharmacological Basis of Therapeutics
- UpToDate: Adjuvant endocrine therapy for breast cancer
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