The Absolute Effect / Evidence / Breast Cancer
BCIRG 006
Clinical question: Does adding trastuzumab to adjuvant chemotherapy improve DFS and OS, and can TCH provide a less cardiotoxic non-anthracycline alternative to AC-TH?
Registry: NCT00021255 · One underlying study; aliases and follow-up publications consolidated.
Design, population and eligibility
International, open-label, randomized phase III trial with three adjuvant chemotherapy arms.
3,222 patients with HER2-positive early breast cancer at high risk; randomized to AC-T, AC-TH or TCH.
Operable HER2-positive early breast cancer with high-risk features, including node-positive disease or node-negative disease meeting protocol risk criteria.
Ten-year follow-up reported in an AACR/SABCS abstract; original NEJM report had shorter follow-up. Long-term outcome estimates are mature.
Treatment and comparator
AC-T: doxorubicin 60 mg/m² plus cyclophosphamide 600 mg/m² for four cycles followed by docetaxel 100 mg/m² for four cycles. AC-TH: AC followed by docetaxel with trastuzumab. TCH: docetaxel 75 mg/m², carboplatin AUC 6 and trastuzumab for six cycles. Trastuzumab was continued to complete one year in trastuzumab arms.
Primary and secondary endpoints
Primary endpoint: disease-free survival. Secondary endpoints included overall survival, cardiac safety, symptomatic congestive heart failure and LVEF decline.
Key efficacy results
At approximately 10.3 years, DFS was 67.9% with AC-T, 74.6% with AC-TH and 73.0% with TCH. Relative to AC-T, DFS HR was 0.70 (95% CI 0.60–0.83; p<0.001) for AC-TH and 0.76 (95% CI 0.65–0.90; p<0.001) for TCH.
Ten-year OS was 78.7%, 85.9% and 83.3%, respectively. OS HR versus AC-T was 0.64 (95% CI 0.52–0.79; p<0.001) for AC-TH and 0.76 (95% CI 0.62–0.93; p=0.0081) for TCH. No significant efficacy difference was observed between AC-TH and TCH; the trial was not designed as a formal non-inferiority comparison between these two arms.
Source-reported outcome visualization
Ten-year disease-free survival by randomized arm.
Kaplan–Meier estimates from the 10-year follow-up report. Comparisons versus AC-T were significant; no formal equivalence claim between AC-TH and TCH.
Absolute effect
AC-TH versus AC-T produced a 6.7 percentage-point higher 10-year DFS; approximate NNT 15 at 10 years to prevent one DFS event. TCH versus AC-T produced a 5.1-point difference; approximate NNT 20. These are landmark estimates from Kaplan–Meier rates and should be interpreted with the DFS endpoint definition. No NNT is assigned to TCH versus AC-TH.
Trial-specific toxicity and treatment burden
Symptomatic CHF at long-term follow-up was 2.0% with AC-TH versus 0.4% with TCH (p=0.0005); AC-T had 0.8%. Relative LVEF decline >10% was approximately twice as frequent with AC-TH as TCH (206 versus 97 patients; p<0.0001). Acute leukaemia was rare but occurred predominantly in anthracycline-treated patients.
Anthracycline-containing therapy adds cumulative cardiotoxicity and secondary leukaemia risk; TCH adds carboplatin-associated myelosuppression and neuropathy. The study compared complete regimens, not trastuzumab alone.
Quality of life and patient-reported outcomes
A major comparative QoL benefit was not established as a headline endpoint. Cardiac events, alopecia, neuropathy, marrow suppression and one year of trastuzumab visits are relevant treatment burdens.
Subgroups and applicability
Trastuzumab benefit was observed across clinically relevant risk groups. TOP2A co-amplification was explored, but it is not a validated basis for selecting AC-TH over TCH.
Current-practice context · reviewed 2 November 2026
BCIRG 006 remains important for the efficacy–cardiotoxicity trade-off in adjuvant HER2-positive disease. Non-anthracycline TCH is a widely used option, while contemporary treatment is also shaped by neoadjuvant dual blockade and post-neoadjuvant T-DM1 for residual invasive disease (KATHERINE).
Limitations and critical interpretation
The 10-year comparison between AC-TH and TCH is not a formal non-inferiority test. Long-term estimates are reported in a conference abstract; detailed subgroup and toxicity tables should be interpreted with the full original report and supplementary material. Regimens predate routine pertuzumab and T-DM1 sequencing.
Bottom line: BCIRG 006 establishes the benefit of adjuvant trastuzumab and shows that TCH retains substantial efficacy with markedly less symptomatic cardiac toxicity than AC-TH. It does not prove that the two trastuzumab regimens are formally equivalent.
Primary sources and follow-up publications
- BCIRG 006 primary report, NEJM 2011
- BCIRG 006 10-year follow-up, SABCS 2015 abstract
- BCIRG 006 registry
All outcome values above are transcribed from the linked trial reports or their prespecified follow-up publications. Unreported values are not imputed. No NNT is derived from median survival.