Background
ATAC (Arimidex, Tamoxifen Alone or in Combination). Phase III RCT of 9,366 postmenopausal women with operable early breast cancer evaluating adjuvant anastrozole vs tamoxifen vs the combination.
Interventions and follow up
Arm A: Tamoxifen 20mg/d × 5yr
Arm B: Anastrozole 1mg/d × 5yr
Arm C: Anastrozole 1mg/d + Tamoxifen 20mg/d × 5yr
Primary endpoint: DFS and safety
mFollow up: 33.3mo (initial analysis)
Arm B: Anastrozole 1mg/d × 5yr
Arm C: Anastrozole 1mg/d + Tamoxifen 20mg/d × 5yr
Primary endpoint: DFS and safety
mFollow up: 33.3mo (initial analysis)
Results
3-yr DFS, anastrozole vs tamoxifen: 89.4% vs 87.4% (HR 0.83, 95%CI 0.71-0.96, P=.013).
3-yr DFS, combination arm: 87.2% (no advantage over tamoxifen alone; combination dropped).
Contralateral breast cancer: reduced with anastrozole vs tamoxifen.
3-yr DFS, combination arm: 87.2% (no advantage over tamoxifen alone; combination dropped).
Contralateral breast cancer: reduced with anastrozole vs tamoxifen.
Adverse events
Anastrozole vs tamoxifen vs combination:
Gynecologic/oncologic: endometrial cancer 0.1% vs 0.5% vs 0.3% (P=.02); vaginal bleeding 4.5% vs 8.2% vs 7.7% (P<.0001).
Vascular/thrombotic: cerebrovascular events 1.0% vs 2.1% vs 1.6% (P=.0006); VTE 2.1% vs 3.5% vs 4.0% (P=.0006); DVT 1.0% vs 1.7% vs 2.0% (P=.02).
Vasomotor: hot flushes 34.4% vs 39.7% vs 40.1% (P<.0001).
Musculoskeletal/bone: fractures more frequent with anastrozole (5.9% vs 3.7% vs 4.6%, P<.0001).
Gynecologic/oncologic: endometrial cancer 0.1% vs 0.5% vs 0.3% (P=.02); vaginal bleeding 4.5% vs 8.2% vs 7.7% (P<.0001).
Vascular/thrombotic: cerebrovascular events 1.0% vs 2.1% vs 1.6% (P=.0006); VTE 2.1% vs 3.5% vs 4.0% (P=.0006); DVT 1.0% vs 1.7% vs 2.0% (P=.02).
Vasomotor: hot flushes 34.4% vs 39.7% vs 40.1% (P<.0001).
Musculoskeletal/bone: fractures more frequent with anastrozole (5.9% vs 3.7% vs 4.6%, P<.0001).
Conclusions
Adjuvant anastrozole improved DFS and reduced contralateral breast cancer vs tamoxifen in postmenopausal women, with fewer gynecologic and thrombotic events but more fractures. The combination offered no benefit over tamoxifen alone.
Key Limitations
Initial report at short 33.3mo follow-up; HR+ status not required for all enrolled (benefit confined to HR+ subset). No OS difference at maturity. Combination arm closed early. Fracture risk requires ongoing bone management.
Clinical Context
ATAC was the first large adjuvant trial to establish an aromatase inhibitor over tamoxifen in postmenopausal HR+ disease, leading to anastrozole's adjuvant FDA approval. The 10-yr update (Cuzick, Lancet Oncol 2010) confirmed durable DFS and recurrence benefit. ASCO and ESMO guidelines incorporate an AI into adjuvant therapy for postmenopausal HR+ patients.
References
Baum M et al, Lancet, 2002; PMID: 12090977
Cuzick J et al, Lancet Oncol, 2010 (ATAC 10-yr); PMID: 21087898
Cuzick J et al, Lancet Oncol, 2010 (ATAC 10-yr); PMID: 21087898