Clinical question: In operable HER2-positive breast cancer, does adding trastuzumab to AC→paclitaxel improve survival?
Design: Joint randomized phase III analysis; 4,046 women with HER2-positive operable breast cancer. AC followed by paclitaxel with or without trastuzumab. Median follow-up 8.4 years in the definitive report.
Absolute benefit 8.8 points; NNT ≈ 12 at 10 years.
Absolute benefit 11.5 points; NNT ≈ 9 at 10 years.
OS HR 0.63 (95% CI 0.54–0.73; P<.001); DFS HR 0.60 (0.53–0.68; P<.001). Benefit was observed across prespecified subgroups.
The two cooperative-group trials used the same anthracycline/cyclophosphamide→paclitaxel backbone and were jointly analyzed. Trastuzumab was given concurrently with paclitaxel and continued for one year. This is a superiority trial, so absolute differences and NNT are appropriate.
Cardiac toxicity was the major treatment-specific concern; the regimen demonstrated a small but important increase in cardiovascular events compared with chemotherapy alone. The page does not manufacture an NNH from heterogeneous cardiac definitions when a single clinically coherent time-horizon risk is not available.
This is one of the clearest examples of a targeted therapy producing a large durable absolute survival effect in early breast cancer. At 10 years, treating approximately 9 patients produces one additional DFS event avoided and treating approximately 12 produces one additional survivor. The magnitude is larger than the absolute gain seen in HERA, although the populations and analyses differ. Modern non-anthracycline and dual-HER2 regimens mean the historical toxicity profile should not simply be transplanted to current practice.
B-31/N9831 established adjuvant trastuzumab with chemotherapy as a major standard for HER2-positive early breast cancer. Current care may add pertuzumab for higher-risk node-positive disease, use neoadjuvant treatment to assess response, and switch to T-DM1 for residual invasive disease; cardiac risk and modern HER2-directed sequencing matter.