In a postmenopausal woman with estrogen‑receptor‑positive stage I–II breast cancer, how many patients need to be treated with anastrozole (Arimidex) to prevent one recurrence (or one breast‑cancer‑related death)?

Number Needed to Treat with Anastrozole in Stage I-II Breast Cancer

Based on the landmark ATAC trial with 10-year follow-up, approximately 23 postmenopausal women with hormone receptor-positive stage I-II breast cancer need to be treated with anastrozole for 5 years to prevent one recurrence compared to tamoxifen. 1

Calculating NNT from ATAC Trial Data

The most robust data comes from the ATAC trial's 10-year analysis in hormone receptor-positive patients:

• Absolute risk reduction for recurrence: 4.3% at 10 years (time to recurrence endpoint) 1
• NNT calculation: 1 ÷ 0.043 = 23 patients need treatment to prevent one recurrence 1
• At 5 years, the absolute difference was smaller at 2.7%, yielding an NNT of approximately 37 1

Context: Anastrozole vs. Placebo in High-Risk Women

For prevention in high-risk postmenopausal women without cancer (IBIS-II trial):

• Absolute risk reduction: 2.8% (5.6% placebo vs 2.8% anastrozole at 7 years) 2
• NNT: Approximately 36 women need treatment for 5 years to prevent one breast cancer 2
• This represents a 53% relative risk reduction (HR 0.47) 2

Mortality Benefit: The Critical Limitation

Anastrozole does NOT improve overall survival in stage I-II breast cancer patients compared to tamoxifen. 1

• After 10 years of follow-up in ATAC, overall mortality showed no significant difference (HR 0.95% CI 0.84-1.06, p=0.4) 1
• There was only weak evidence of fewer deaths after recurrence (HR 0.87,95% CI 0.74-1.02, p=0.09) 1
• Extended therapy beyond 5 years improves disease-free survival but not overall survival 3, 4

Sequential Therapy: Alternative Approach

Switching from tamoxifen to anastrozole after 2-3 years provides survival benefit:

• ARNO 95 trial: Switching showed improved overall survival (HR 0.53,95% CI 0.28-0.99, p=0.045) 5
• Meta-analysis of switching trials: Overall survival HR 0.71 (95% CI 0.52-0.98, p=0.04) 5
• This suggests sequential therapy may be superior to anastrozole alone for mortality outcomes 5

Extended Therapy (10 Years Total)

For patients completing 5 years of endocrine therapy:

• AERAS trial: Extending anastrozole to 10 years improved 5-year DFS from 86% to 91% 4
• Absolute benefit: 5% improvement in disease-free survival 4
• NNT: Approximately 20 patients need extended therapy to prevent one recurrence 4
• Node-positive patients derive the most substantial benefit with 34% relative risk reduction 3

Quality of Life Trade-offs

The NNT must be weighed against significant toxicity:

• Fracture risk: 7.1% with anastrozole vs 4.1% with tamoxifen (NNH = 33) 1
• Musculoskeletal symptoms: Occur in 25-30% of patients, leading cause of discontinuation 6
• Bone mineral density loss: Significant decreases in spine and hip during treatment 1
• Fracture risk returns to baseline after treatment completion 1

Clinical Decision Algorithm

For standard 5-year therapy:

• Use anastrozole as initial therapy in postmenopausal women with HR-positive stage I-II breast cancer 5
• NNT = 23 to prevent one recurrence at 10 years 1
• No mortality benefit over tamoxifen 1

For extended therapy (years 5-10):

• Offer to node-positive patients (strongest benefit, 34% RRR) 3
• Consider for high-risk node-negative (young age, high-grade tumors) 3
• NNT = 20 to prevent one recurrence 4
• Do not extend beyond 10 years total (no evidence of benefit) 3

Contraindications to anastrozole:

• Severe osteoporosis (T-score <-4) is a relative contraindication 6
• Consider tamoxifen instead in patients with significant bone disease 6

Mandatory Monitoring

• Baseline bone density measurement before starting treatment 3, 6
• Calcium and vitamin D supplementation for all patients 3, 6
• Bisphosphonates or RANKL inhibitors for moderate bone loss 6
• Regular assessment for musculoskeletal symptoms that may require switching therapy 6