What is the recommended duration of anastrozole (aromatase inhibitor) therapy for a postmenopausal woman with hormone receptor-positive breast cancer and no significant medical history?

Anastrozole Duration for Hormone Receptor-Positive Breast Cancer

Postmenopausal women with hormone receptor-positive breast cancer should receive anastrozole for 5 years as standard therapy, with extension to 10 years total for node-positive disease and consideration of extension for higher-risk node-negative disease. 1, 2

Standard 5-Year Duration

• The FDA-approved dose is anastrozole 1 mg daily for 5 years as adjuvant treatment for early breast cancer in postmenopausal women. 3
• Five years of anastrozole as initial therapy provides superior disease-free survival compared to tamoxifen alone, with a hazard ratio of 0.87 (95% CI, 0.78–0.97; P = .01) and time to recurrence HR of 0.79 (95% CI, 0.70–0.90; P = .0005). 4
• This 5-year standard applies to all postmenopausal women with hormone receptor-positive disease receiving aromatase inhibitor therapy. 4, 3

Extended Therapy to 10 Years: Patient Selection

Node-positive patients derive the most substantial benefit from extended therapy and should be offered treatment up to 10 years total. 1, 2, 5

• Extended anastrozole from 5 to 10 years reduces disease recurrence by 34% (HR 0.66; 95% CI, 0.48-0.91), with 5-year disease-free survival of 95% versus 91% with 5 years only. 5, 6
• The absolute benefit translates to a 4% improvement in disease-free survival over 5 years of follow-up. 5
• Extended therapy particularly reduces local recurrence (10 vs 27 events) and second primary cancers (27 vs 52 events). 6

Higher-risk node-negative patients should consider extension based on established prognostic factors including young age and high-grade tumors. 1, 2

• Many node-negative patients may benefit from extended therapy up to 10 years based on recurrence risk assessment. 1
• Low-risk node-negative patients should not routinely receive extended therapy, as absolute benefits are narrow and may not justify ongoing toxicity. 1, 5

Maximum Duration: Do Not Exceed 10 Years

Women should receive no more than 10 years of total endocrine treatment. 1, 2, 5

• There is no evidence supporting benefit beyond 10 years, and toxicity accumulates over time. 1, 2
• One high-quality 2021 trial (ABCSG-16/SALSA) directly compared 7 years versus 10 years of anastrozole and found no benefit for the longer duration (HR 0.99; 95% CI, 0.85-1.15; P = 0.90). 7
• The 10-year group in this trial had significantly higher bone fracture risk (HR 1.35; 95% CI, 1.00-1.84) without any disease-free survival advantage. 7

Benefits of Extended Therapy

Extended anastrozole provides two major benefits beyond 5 years:

• Reduced distant recurrence risk: 34% relative risk reduction in disease recurrence. 2, 5
• Prevention of contralateral breast cancer: 58% relative risk reduction in new opposite-breast cancers (annual incidence 0.21% vs 0.49%). 2, 5

Extended therapy does not improve overall survival—it only prevents recurrence and second cancers. 1, 2, 5, 6

• Five-year overall survival was 93% with extended therapy versus 94% with placebo (HR 0.97; P=0.83). 5
• This lack of overall survival benefit must be weighed against ongoing toxicity when counseling patients. 1

Toxicity Considerations for Extended Therapy

Bone-related adverse events significantly increase with extended anastrozole therapy:

• Bone fractures increase from 9% to 14% with extended therapy. 5, 7
• New-onset osteoporosis increases from 6% to 11%. 5
• Bone pain affects 18% versus 14% with extended versus standard duration. 5
• The ABCSG-16 trial showed a 35% increased fracture risk with 10 versus 7 years (HR 1.35). 7

Other toxicity considerations:

• Cardiovascular events show a trend toward increased risk (OR 1.18). 1, 2
• Quality of life worsens in physical role functioning compared to placebo during extended therapy. 1, 5
• Musculoskeletal symptoms including joint stiffness and arthralgia are common throughout treatment. 2
• Grade ≥3 adverse events remain <1% in both standard and extended therapy groups. 6

Common Pitfalls to Avoid

• Do not extend therapy beyond 10 years total—no evidence supports benefit beyond this duration, and the 2021 ABCSG-16 trial definitively showed no advantage for 10 versus 7 years. 1, 2, 7
• Do not automatically extend therapy in all node-negative patients—carefully assess recurrence risk using established prognostic factors before recommending extension. 1, 2
• Do not ignore bone health monitoring—the increased fracture risk is substantial and requires proactive management with calcium, vitamin D supplementation, regular exercise, and consideration of bisphosphonates. 2, 5
• Do not use aromatase inhibitors in premenopausal women—serial assessment of luteinizing hormone, follicle-stimulating hormone, and estradiol is mandatory to confirm true postmenopausal status in women who become amenorrheic with chemotherapy. 4