What is the use of Anastrozole in postmenopausal women with hormone receptor-positive breast cancer?

Anastrozole in Postmenopausal Women with Hormone Receptor-Positive Breast Cancer

Anastrozole 1 mg daily for 5 years is the first-line adjuvant endocrine therapy for postmenopausal women with hormone receptor-positive early breast cancer, demonstrating superior disease-free survival, reduced recurrence rates, and a more favorable safety profile compared to tamoxifen, particularly regarding life-threatening complications like endometrial cancer and thromboembolic events. 1, 2

FDA-Approved Indications

Anastrozole is FDA-approved for three specific uses in postmenopausal women: 2

• Adjuvant treatment of hormone receptor-positive early breast cancer 2
• First-line treatment of hormone receptor-positive or hormone receptor unknown locally advanced or metastatic breast cancer 2
• Second-line treatment of advanced breast cancer following tamoxifen failure 2

Mechanism of Action and Efficacy

Anastrozole is a selective non-steroidal aromatase inhibitor that blocks conversion of adrenal androgens to estrone and estradiol in peripheral tissues, reducing serum estradiol by approximately 70% within 24 hours and 80% after 14 days. 2

Key efficacy outcomes demonstrate clear superiority over tamoxifen: 1

• 17% reduction in disease recurrence (HR 0.83,95% CI 0.73-0.94, P=0.005) at 68 months median follow-up 1
• 26% reduction in time to recurrence (HR 0.74,95% CI 0.64-0.87, P=0.0002) 1
• 93.1% vs 89.1% 10-year breast cancer-free interval compared to tamoxifen (HR 0.73,95% CI 0.56-0.96, P=0.0234) 1

Current Guideline Recommendations

Major guideline organizations (NCCN, ASCO, St Gallen) uniformly recommend aromatase inhibitors as part of optimal adjuvant therapy for postmenopausal women with hormone receptor-positive breast cancer. 3

Three evidence-based treatment strategies are equally recommended: 3

• Initial adjuvant therapy with anastrozole or letrozole for 5 years 3
• Switching after 2-3 years of tamoxifen to anastrozole or exemestane to complete 5 years 3
• Extended therapy with letrozole after approximately 5 years of tamoxifen 3

Tamoxifen alone should only be used in women who decline, have contraindications to, or cannot tolerate aromatase inhibitors. 3

Critical Population Restriction

Anastrozole is absolutely contraindicated in premenopausal women. 4, 2

• Aromatization of adrenal androgens is not a significant source of estradiol in premenopausal women, making anastrozole ineffective in this population 4, 2
• Serial assessment of luteinizing hormone, follicle-stimulating hormone, and estradiol is mandatory to confirm true postmenopausal status before initiating treatment 4
• Anastrozole should never be prescribed for breast cancer risk reduction in premenopausal women 5

Safety Profile Advantages Over Tamoxifen

Anastrozole demonstrates significantly fewer life-threatening complications: 1

• 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
• Less vaginal bleeding: 5.4% vs 10.2% (P<0.0001) 1
• Fewer hot flushes: 35.7% vs 40.9% (P<0.0001) 1
• Lower treatment discontinuation: 11.1% vs 14.3% (P=0.0002) 1

Bone Health: The Primary Safety Concern

Anastrozole significantly increases fracture risk (10% vs 7% compared to tamoxifen), representing the most important adverse effect requiring proactive management. 4, 2

Mandatory Pre-Treatment Evaluation

• Evaluate baseline fracture risk and measure bone mineral density before initiating anastrozole 4, 5
• Women with severe osteoporosis should not receive anastrozole 4

Essential Bone Protection Strategy

All patients receiving anastrozole require: 4, 5

• Comprehensive bone protection with calcium and vitamin D supplementation 4, 5
• Regular weight-bearing exercise 4, 5
• Consider bone-protective agents (bisphosphonates, RANKL inhibitors) for patients at risk 5
• Interval bone mineral density monitoring during treatment 4

Other Important Side Effects

Patients must be counseled about: 4, 5

• Joint stiffness and arthralgias 4, 5
• Vasomotor symptoms 4, 5
• Hypertension 4, 5
• Dry eyes and vaginal dryness 4, 5
• Cardiovascular events in women with pre-existing heart disease 4, 2

Critical Drug Interactions and Contraindications

Never combine anastrozole with tamoxifen - the combination is no better than tamoxifen alone and reduces anastrozole plasma concentrations by 27%. 1, 2

Anastrozole should not be taken with: 2

• Hormone replacement therapy 2
• Birth control pills 2
• Estrogen creams, vaginal rings, or vaginal suppositories 2

Dosing and Administration

• Standard dose: 1 mg orally once daily 5, 2
• Duration: 5 years for adjuvant treatment 5
• Can be taken with or without food 2
• No dose adjustments needed for hepatic or renal impairment 2

Monitoring Requirements

• Interval history and physical examination every 6-12 months for 5 years, then annually 4
• Annual diagnostic mammography 4
• Serial bone mineral density assessments 4, 5

When Anastrozole Rarely Works

Patients with ER-negative disease and those who did not respond to previous tamoxifen therapy rarely respond to anastrozole. 1, 2 Benefits are most pronounced in hormone receptor-positive disease. 1

Stopping Treatment

After completing 5 years of treatment, anastrozole can be stopped directly without tapering. 4 Continue calcium and vitamin D supplementation if bone density is compromised, maintain weight-bearing exercise, and continue standard mammographic surveillance. 4