Introduction
Anastrozole is a potent, nonsteroidal aromatase inhibitor used primarily in the treatment of hormone receptor-positive breast cancer in postmenopausal women. As a third-generation aromatase inhibitor, it represents a significant advancement in endocrine therapy for breast cancer, offering improved specificity and reduced side effects compared to earlier generations of hormonal therapies.
Mechanism of Action
Anastrozole exerts its therapeutic effect through competitive, reversible inhibition of the aromatase enzyme system. This enzyme complex, primarily located in adipose tissue, muscle, liver, and breast tissue, is responsible for the conversion of androgens (particularly androstenedione and testosterone) to estrogens (estrone and estradiol). By inhibiting aromatase, anastrozole significantly reduces circulating estrogen levels in postmenopausal women by approximately 70-80%, thereby depriving estrogen-dependent breast cancer cells of their primary growth stimulus.
Indications
- Adjuvant treatment of hormone receptor-positive early breast cancer in postmenopausal women
- First-line treatment of hormone receptor-positive or hormone receptor unknown locally advanced or metastatic breast cancer in postmenopausal women
- Treatment of advanced breast cancer in postmenopausal women with disease progression following tamoxifen therapy
Dosage and Administration
Standard adult dosage: 1 mg orally once daily Administration: Can be taken with or without food Duration: Continued for 5 years in adjuvant setting or until disease progression in advanced disease Special populations:- Renal impairment: No dosage adjustment necessary
- Hepatic impairment: Use with caution in moderate to severe impairment
- Pediatrics: Not indicated for use in children
- Geriatrics: No dosage adjustment necessary
Pharmacokinetics
Absorption: Well absorbed orally with bioavailability of 83-85%; food slightly decreases rate but not extent of absorption Distribution: Volume of distribution approximately 83-87 L; 40% plasma protein binding Metabolism: Extensive hepatic metabolism primarily via N-dealkylation, hydroxylation, and glucuronidation via multiple cytochrome P450 enzymes (CYP3A4, CYP3A5, and CYP2C8) Elimination: Primarily hepatic; elimination half-life approximately 50 hours; 85% excreted via feces, 11% via urine Steady-state: Achieved after approximately 7 days of repeated dosingContraindications
- Premenopausal women
- Pregnancy or suspected pregnancy
- Patients with known hypersensitivity to anastrozole or any component of the formulation
- Patients with estrogen receptor-negative breast cancer who have not responded to previous tamoxifen therapy
Warnings and Precautions
- Bone effects: Significant reduction in bone mineral density may occur; monitor bone density and consider prophylactic treatment
- Cardiovascular effects: Increased incidence of ischemic cardiovascular events observed in clinical trials
- Cholesterol effects: May cause elevation in total cholesterol and LDL cholesterol
- Hepatic impairment: Use with caution in patients with moderate to severe hepatic impairment
- CYP2C19 poor metabolizers: May have increased drug exposure; monitor for adverse effects
Drug Interactions
- Estrogen-containing therapies: May interfere with pharmacological action; concomitant use contraindicated
- Tamoxifen: Coadministration reduces anastrozole plasma concentrations by 27%; avoid combination
- CYP3A4 inducers: Drugs such as rifampin, carbamazepine, and St. John's wort may decrease anastrozole concentrations
- CYP2C8 inhibitors: May increase anastrozole exposure
- Oral contraceptives: Not recommended due to potential interference with efficacy
Adverse Effects
Very common (≥10%):- Hot flashes (35%)
- Asthenia (19%)
- Arthralgia (17%)
- Pain (15%)
- Nausea (11%)
- Headache (13%)
- Rash (11%)
- Vaginal dryness
- Hair thinning
- Diarrhea
- Somnolence
- Hypertension
- Depression
- Osteoporosis
- Hypercholesterolemia
- Anaphylactoid reactions
- Severe cutaneous adverse reactions
- Hepatic events (elevated transaminases)
- Angioedema
- Ischemic cardiovascular events
Monitoring Parameters
- Baseline and periodic: Bone mineral density (every 1-2 years)
- Regular monitoring: Liver function tests, lipid profile
- Clinical assessment: Regular evaluation for arthralgia, musculoskeletal symptoms
- Cancer monitoring: Regular imaging and tumor marker assessment as clinically indicated
- Symptom management: Assessment and management of vasomotor symptoms
Patient Education
- Take medication exactly as prescribed at the same time each day
- Report any new or worsening bone pain, joint stiffness, or mobility issues
- Notify healthcare provider of hot flashes, vaginal dryness, or other menopausal symptoms
- Maintain adequate calcium and vitamin D intake
- Engage in regular weight-bearing exercise to maintain bone health
- Report any signs of allergic reaction (rash, swelling, difficulty breathing)
- Inform all healthcare providers of anastrozole use, especially before starting new medications
- Use effective non-hormonal contraception if sexually active and premenopausal
- Attend all scheduled follow-up appointments and screening tests
References
1. National Comprehensive Cancer Network. Breast Cancer Guidelines Version 3.2023 2. FDA Prescribing Information: Anastrozole Tablets 3. Early Breast Cancer Trialists' Collaborative Group. Aromatase inhibitors versus tamoxifen in early breast cancer. Lancet 2015 4. Baum M, et al. Anastrozole alone or in combination with tamoxifen versus tamoxifen alone for adjuvant treatment of postmenopausal women with early breast cancer. Cancer 2003 5. Bundred NJ, et al. The effect of anastrozole on bone mineral density. Journal of Clinical Oncology 2008 6. ATAC Trialists' Group. Results of the ATAC trial after completion of 5 years. Lancet Oncology 2008 7. Micromedex Solutions. Anastrozole Drug Information 8. American Society of Clinical Oncology. Management of Aromatase Inhibitor-Associated Bone Loss. JCO 2022