Background
12,894 women with early breast cancer who had completed 5 years of tamoxifen were randomized to continue to 10 years or stop at 5 years; analyses focused on ER-positive disease.
Interventions and follow up
Arm A: Tamoxifen 20 mg daily for 10 years
Arm B: Tamoxifen 20 mg daily for 5 years (stop)
Primary endpoint: Recurrence and breast cancer mortality
mFollow up: 15yr
Arm B: Tamoxifen 20 mg daily for 5 years (stop)
Primary endpoint: Recurrence and breast cancer mortality
mFollow up: 15yr
Results
Recurrence (yr 5-14, 10yr vs 5yr): 21.4% vs 25.1% (absolute reduction 3.7%)
Breast cancer mortality (yr 5-14): 12.2% vs 15.0% (absolute reduction 2.8%)
Endometrial cancer (yr 5-14): 3.1% (mortality 0.4%) vs 1.6% (mortality 0.2%) for 10 vs 5 years
Breast cancer mortality (yr 5-14): 12.2% vs 15.0% (absolute reduction 2.8%)
Endometrial cancer (yr 5-14): 3.1% (mortality 0.4%) vs 1.6% (mortality 0.2%) for 10 vs 5 years
Adverse events
Thromboembolic: Pulmonary embolus RR 1.87 (95% CI 1.13-3.07, P=.01); stroke 1.06 (0.83-1.36).
Cardiac: Ischemic heart disease 0.76 (0.60-0.95, P=.02).
Gynecologic: Endometrial cancer 1.74 (1.30-2.34, P=.0002).
Cardiac: Ischemic heart disease 0.76 (0.60-0.95, P=.02).
Gynecologic: Endometrial cancer 1.74 (1.30-2.34, P=.0002).
Conclusions
Extending tamoxifen to 10 years reduces recurrence (3.7%) and breast cancer mortality (2.8%) versus 5 years, at the cost of increased PE and endometrial cancer risk.
Key Limitations
Benefit emerges late (carryover effect after year 10), requiring long follow-up. Heterogeneous nodal/ER status and adjuvant therapy. Predominantly premenopausal-relevant given tamoxifen focus; aromatase-inhibitor extension data come from separate trials (MA.17).
Clinical Context
With aTTom, established 10 years of adjuvant tamoxifen as an option for ER-positive early breast cancer (ASCO/ESMO endocrine-therapy guidance), informing extended-endocrine-therapy decisions weighed against thromboembolic and endometrial risk.