What are the indications, recommended dose, contraindications, common adverse effects, and monitoring requirements for anastrozole in postmenopausal women with estrogen‑receptor‑positive breast cancer?

Anastrozole in Postmenopausal Women with Hormone Receptor-Positive Breast Cancer

Primary Indication

Anastrozole 1 mg daily is the first-line adjuvant endocrine therapy for postmenopausal women with estrogen receptor-positive early breast cancer, demonstrating superior disease-free survival and a more favorable safety profile compared to tamoxifen. 1

Recommended Dosing

• Standard therapy: Anastrozole 1 mg orally once daily for 5 years as initial adjuvant treatment 1, 2
• Extended therapy: Continue anastrozole for a total of 10 years in appropriate candidates, which increases 5-year disease-free survival by an absolute 5% (from 86% to 91%), with the number needed to treat being approximately 20 patients to prevent one recurrence 2
• Sequential therapy: Switch from tamoxifen to anastrozole after 2-3 years of tamoxifen, which improves overall survival (HR 0.53; 95% CI 0.28-0.99; P=0.045) and may be superior to anastrozole monotherapy for mortality outcomes 2, 3
• Do not extend beyond 10 years, as no additional benefit has been demonstrated 2
• Node-positive patients derive the greatest benefit from extended therapy, with a 34% relative risk reduction for recurrence 2

Absolute Contraindications

• Premenopausal status – aromatase inhibitors do not adequately suppress ovarian estrogen synthesis in premenopausal women, making anastrozole ineffective and potentially harmful in this population 1

Relative Contraindications

• Severe osteoporosis (T-score <-4 or >2 vertebral fractures) – tamoxifen should be considered instead 2, 4
• Pre-existing severe ischemic heart disease – requires close monitoring due to increased stroke risk 4

Common Adverse Effects

Musculoskeletal (Most Common Cause of Discontinuation)

• Joint stiffness and arthralgias occur in 25-30% of patients and are the leading reason for treatment discontinuation 2, 4
• Myalgia occurs more frequently than with tamoxifen 5, 4

Bone Health (Most Serious Quality-of-Life Threat)

• Increased fracture risk – 7.1% with anastrozole vs 4.1% with tamoxifen after 37 months, particularly affecting spine, hip, and wrist 4
• Decreased bone mineral density in both lumbar spine and hip compared to baseline 4

Vasomotor Symptoms

• Hot flashes occur in 35.7% (vs 40.9% with tamoxifen), though still very common 1, 4
• Night sweats are common 4

Genitourinary

• Vaginal dryness and dyspareunia occur more frequently than with tamoxifen 4
• Less vaginal bleeding (5.4% vs 10.2% with tamoxifen) and less vaginal discharge (3.5% vs 13.2% with tamoxifen) 1

Cardiovascular and Metabolic

• Increased stroke risk compared to tamoxifen (2.0% vs 2.8%) 1, 4
• Hypercholesterolemia occurs more frequently than with tamoxifen 5, 4

Other Common Effects

• Peripheral edema (leg/ankle swelling) 4, 6
• Dry eyes 4
• Depression in a significant proportion 4
• Gastrointestinal disturbances (29-33%), generally mild and transient 6
• Headache (≤18%), asthenia (≤16%), pain (≤15%) 6

Advantages Over Tamoxifen

• Significantly lower endometrial cancer risk – 0.2% vs 0.8% (P=0.02) 1
• Reduced thromboembolic events – 2.8% vs 4.5% (P=0.0004) 1
• Fewer cerebrovascular events – 2.0% vs 2.8% (P=0.03) 1
• Lower treatment discontinuation due to adverse effects – 11.1% vs 14.3% (P=0.0002) 1
• 17% reduction in disease recurrence at 68 months (HR 0.83; 95% CI 0.73-0.94; P=0.005) 1
• 26% reduction in time to recurrence (HR 0.74; 95% CI 0.64-0.87; P=0.0002) 1

Mandatory Monitoring Requirements

Before Initiating Therapy

• Baseline bone mineral density assessment (dual-energy X-ray absorptiometry/DEXA scan) is mandatory before starting anastrozole 2
• Confirm postmenopausal status – this is non-negotiable as the drug is ineffective in premenopausal women 1, 4

During Therapy

• Regular bone density monitoring throughout treatment 2
• Regular evaluation for musculoskeletal adverse effects with option to switch therapy if intolerable 2
• Monitor for cardiovascular risk factors, particularly in patients with pre-existing heart disease 4

Mandatory Supportive Care

• All patients must receive calcium and vitamin D supplementation to support bone health 2
• Weight-bearing exercise should be encouraged 4
• Consider bisphosphonates or RANK-ligand inhibitors in patients with moderate bone loss 2, 4

Critical Clinical Pitfalls to Avoid

• Never combine anastrozole with tamoxifen – the combination is no better than tamoxifen alone and reduces anastrozole plasma concentrations by 27% 1
• Never use in premenopausal women without ovarian suppression – it will not work 1
• Do not prescribe without bone protection measures – fracture risk is the most serious quality-of-life threatening complication 4
• Patients with ER-negative disease rarely respond to anastrozole – benefits are restricted to hormone receptor-positive disease 1

Special Population Considerations

• Younger postmenopausal patients (<60 years) derive particular benefit, with improved breast cancer-free interval 5, 1
• Patients with concerns about embolism are especially appropriate candidates for anastrozole over tamoxifen 5
• DCIS patients: Anastrozole provides at least comparable benefit to tamoxifen in postmenopausal women with hormone receptor-positive DCIS after breast-conserving therapy (category 1 evidence with radiotherapy; category 2A with excision alone) 5