Clinical question: In HER2-positive early breast cancer after chemotherapy, does 1 year of adjuvant trastuzumab improve long-term outcomes versus observation?
Design: International multicentre open-label phase III randomized trial; 5,102 women enrolled, 5,099 in ITT; observation vs 1 year vs 2 years trastuzumab. Median follow-up 11 years.
Trastuzumab for 1 year (18 cycles, every 3 weeks) after completion of chemotherapy versus observation. The 2-year arm is included to establish duration.
Absolute benefit 6 percentage points; NNT ≈ 17 at 10 years.
Approximate absolute benefit 6 points; NNT ≈ 17 at 10 years.
1-year trastuzumab vs observation: DFS HR 0.76 (95% CI 0.68–0.86); death HR 0.74 (0.64–0.86). Two years did not improve DFS versus one year: HR 1.02 (0.89–1.17).
Secondary cardiac endpoints: 4.4% with 1-year trastuzumab vs 0.9% observation; absolute excess 3.5 points, NNH ≈ 29. Two-year trastuzumab: 7.3%.
The primary long-term comparison is intention-to-treat. Interpretation is affected by selective crossover: 884 (52%) observation patients subsequently received trastuzumab, which likely diluted the observed long-term treatment effect.
HERA established that one year of trastuzumab after chemotherapy produces a durable absolute improvement in disease-free and overall survival. The important quantitative message is that the long-term DFS gain is about 6 percentage points, while extending trastuzumab from one to two years adds no meaningful DFS benefit and increases cardiac exposure. In contemporary practice the chemotherapy backbone and HER2-directed combinations have evolved, but HERA remains the foundational duration trial.
HERA established one year of adjuvant trastuzumab as a foundational treatment for HER2-positive early breast cancer; extending treatment to two years did not provide a corresponding added benefit and increased cardiac/treatment burden. Contemporary decisions incorporate neoadjuvant response, residual disease (including T-DM1), nodal risk, pertuzumab eligibility and cardiac function rather than treating HERA as the only modern HER2-directed strategy.
HERA / BIG 1-01 primary/long-term source ↗ · Current guideline guidance ↗