Background
Tamoxifen Exemestane Adjuvant Multinational (TEAM) trial. Phase III open-label RCT of 9,779 postmenopausal women with HR+ early breast cancer comparing upfront exemestane with a sequential tamoxifen-to-exemestane strategy.
Interventions and follow up
Arm A: Exemestane 25mg/d × 5yr
Arm B: Tamoxifen 20mg/d × 2.5-3yr then Exemestane 25mg/d to complete 5yr
Primary endpoint: 5-yr DFS
mFollow up: 5.1yr
Arm B: Tamoxifen 20mg/d × 2.5-3yr then Exemestane 25mg/d to complete 5yr
Primary endpoint: 5-yr DFS
mFollow up: 5.1yr
Results
5-yr DFS, exemestane vs sequential: 86% vs 85% (HR 0.97, 95%CI 0.88-1.08, P=.60).
5-yr OS, exemestane vs sequential: 91% vs 91% (HR 1.00, 95%CI 0.89-1.14, P>.99).
5-yr OS, exemestane vs sequential: 91% vs 91% (HR 1.00, 95%CI 0.89-1.14, P>.99).
Adverse events
Exemestane vs sequential treatment:
Gynecologic/vascular: gynecologic symptoms 11% vs 20%; VTE <1% vs 2%; endometrial abnormalities 1% vs 4% (all higher with the tamoxifen-containing sequential arm).
Musculoskeletal: musculoskeletal events 50% vs 44% (higher with upfront exemestane).
Cardiovascular/metabolic: hypertension 6% vs 5%; hyperlipidemia 5% vs 3%.
Gynecologic/vascular: gynecologic symptoms 11% vs 20%; VTE <1% vs 2%; endometrial abnormalities 1% vs 4% (all higher with the tamoxifen-containing sequential arm).
Musculoskeletal: musculoskeletal events 50% vs 44% (higher with upfront exemestane).
Cardiovascular/metabolic: hypertension 6% vs 5%; hyperlipidemia 5% vs 3%.
Conclusions
Upfront exemestane and a sequential tamoxifen-to-exemestane strategy yielded equivalent 5-yr DFS and OS; both are acceptable adjuvant approaches, with toxicity profiles differing by the endocrine agent used.
Key Limitations
Open-label design; equivalence outcome with no efficacy separation at 5.1yr (short for late-recurring HR+ disease). Both arms ultimately received exemestane, limiting any inference about AI vs tamoxifen monotherapy.
Clinical Context
TEAM, alongside BIG 1-98, shows that upfront AI and sequential AI/tamoxifen strategies are similarly effective when an AI is included. ASCO and ESMO guidelines accept either approach for postmenopausal HR+ patients, with the choice driven by tolerability and individual risk factors (e.g., thrombotic vs bone risk).