What is the recommended treatment and dosage of Arimidex (anastrozole) for a postmenopausal woman with hormone receptor-positive breast cancer?

Arimidex (Anastrozole) for Postmenopausal Hormone Receptor-Positive Breast Cancer

Postmenopausal women with hormone receptor-positive breast cancer should receive anastrozole 1 mg orally once daily for 5 years as adjuvant therapy, either as initial treatment or after 2-3 years of tamoxifen. 1

Standard Dosing Regimen

• The FDA-approved dose is 1 mg tablet taken once daily, with or without food 1
• The optimal treatment duration is 5 years for adjuvant therapy of early breast cancer 2, 1
• No dosage adjustment is required for renal impairment or elderly patients 1
• No dosage adjustment needed for mild-to-moderate hepatic impairment, though anastrozole has not been studied in severe hepatic impairment 1

Treatment Strategy Options

The American Society of Clinical Oncology and NCCN guidelines recommend three evidence-based approaches, all with equal category 1 evidence 3:

1. Initial adjuvant therapy: Anastrozole for 5 years as primary treatment 4, 5
2. Sequential therapy: 2-3 years of tamoxifen followed by switching to anastrozole to complete 5 years total 3, 5
3. Extended therapy: Anastrozole after completing 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

Efficacy Evidence Supporting Anastrozole

Disease-Free Survival and Recurrence Reduction

• Anastrozole reduces disease recurrence by 17% compared to tamoxifen (HR 0.83,95% CI 0.73-0.94, P=0.005) at 68 months follow-up 4
• Time to recurrence is reduced by 26% with anastrozole (HR 0.74,95% CI 0.64-0.87, P=0.0002) 4
• The ATAC trial demonstrated superior disease-free survival with anastrozole versus tamoxifen at 100 months median follow-up 3
• Contralateral breast cancer risk is significantly reduced with anastrozole (1.9% vs 2.8%, HR 0.68,95% CI 0.49-0.94, P=0.02) 3

Quality of Life and Safety Advantages

Anastrozole demonstrates a superior safety profile compared to tamoxifen for life-threatening complications:

• Endometrial cancer: 0.2% vs 0.8% (P=0.02) 4, 5
• Thromboembolic events: 2.8% vs 4.5% (P=0.0004) 4, 5
• Cerebrovascular events: 2.0% vs 2.8% (P=0.03) 4, 5
• Vaginal bleeding: 5.4% vs 10.2% (P<0.0001) 4
• Hot flushes: 35.7% vs 40.9% (P<0.0001) 4
• Treatment discontinuation due to adverse effects: 11.1% vs 14.3% (P=0.0002) 4

Disadvantages Compared to Tamoxifen

• Bone fractures: 11.0% vs 7.7% (P<0.0001) 5
• Arthralgias/joint stiffness: 35.6% vs 29.4% (P<0.0001) 2, 5

Critical Clinical Caveats

Absolute Contraindications

Never prescribe anastrozole to premenopausal women - aromatase inhibitors do not adequately suppress ovarian estrogen synthesis in premenopausal women, making them ineffective and potentially harmful 4, 5

For women who become amenorrheic with chemotherapy, serial assessment of luteinizing hormone, follicle-stimulating hormone, and estradiol is mandatory to confirm true postmenopausal status before initiating anastrozole 5

Drug Interactions

Never combine anastrozole with tamoxifen - the combination is no better than tamoxifen alone and reduces anastrozole plasma concentrations by 27% 4

Receptor Status Requirements

• Anastrozole is indicated for hormone receptor-positive early breast cancer 1
• Patients with ER-negative disease rarely respond to anastrozole 4, 1
• For advanced disease, anastrozole can be used in hormone receptor-positive or hormone receptor unknown disease 1

Bone Health Management

Prior to initiating anastrozole, evaluate baseline fracture risk and measure bone mineral density 2

Bone Protection Strategy

• Consider bone-protective agents (bisphosphonates or RANKL inhibitors) for patients at risk 2
• All patients should exercise regularly 2
• Ensure adequate calcium and vitamin D supplementation 2
• Use caution in postmenopausal women with moderate bone mineral density loss 2

Patient Counseling on Side Effects

Inform patients about expected side effects 2:

• Joint stiffness and arthralgias
• Vasomotor symptoms (hot flushes)
• Hypertension
• Dry eyes
• Vaginal dryness

Indications Across Disease Spectrum

Anastrozole is FDA-approved for 1:

1. Adjuvant treatment of postmenopausal women with hormone receptor-positive early breast cancer
2. First-line treatment of postmenopausal women with hormone receptor-positive or unknown locally advanced or metastatic breast cancer
3. Second-line treatment of advanced breast cancer in postmenopausal women with disease progression following tamoxifen therapy

Treatment Duration and Continuation

• For early breast cancer: Continue for 5 years 1
• For advanced breast cancer: Continue until tumor progression 1
• The optimal duration beyond 5 years remains under investigation 2