RAPP‐01.

Methods	Randomised controlled trial Multi‐centre (11 French centres) Central randomisation using computerised random number generator. Stratified according to centre, node status, and proliferation Accrual June 1999 to January 2003 Baseline patient and tumour characteristics well balanced Closed prematurely for toxicity in 2003
Participants	Female, premenopausal and postmenopausal Age 18 to 70 years Median age: 52 years (range 26 to 70) Unilateral, operable breast cancer with clear surgical margins 57% limited axillary node positive (≤ 3); 43% high risk node negative Exclusion of metastatic disease HR positive: 80% to 81% in each treatment arm
Interventions	ARM 1 (AT): AT × 4 21‐day cycles (doxorubicin 50 mg/m², docetaxel 75 mg/m²) ARM 2 (AC): AC × 4 21‐day cycles (doxorubicin 60 mg/m², cyclophosphamide 600 mg/m²) Tamoxifen 20 mg/d for 5 years given to all patients with ER and/or PR positive Radiotherapy given as mandatory following breast‐conserving surgery Chemotherapy delivered without primary G‐CSF prophylaxis
Outcomes	Primary endpoint: Disease‐free survival (as stated in 2005 toxicity full‐text article but listed as time to recurrence (TTR) in 2009 abstract) Secondary endpoints: Overall survival Toxicity
Notes	Median follow‐up: 64 months Trial registry record not identified Rene Huguenin Cancer Centre sponsored the trial supported in part by Aventis‐Oncology France and Ligue Regionale Contre le Cancer due Department des Yvelines For the review update, O‐E and V for DFS derived using Method 3 (Tierney 2007)
Risk of bias
Bias	Authors' judgement	Support for judgement
Random sequence generation (selection bias)	Low risk	Stratified randomisation Quote: "using a computerized random‐number generator"
Allocation concealment (selection bias)	Low risk	Central allocation Quote: "central randomization was performed by fax or telephone in the Biostatistics Department of Rene Huguenin Cancer Center (Saint‐Cloud, France)"
Blinding of participants and personnel (performance bias) All outcomes	Unclear risk	Not described
Blinding of outcome assessment ‐ OS (detection bias)	Low risk	Assessment of overall survival unlikely to be influenced by no or incomplete blinding
Blinding of outcome assessment ‐ DFS & Toxicity (detection bias)	Unclear risk	Not described
Incomplete outcome data (attrition bias) All outcomes	Unclear risk	No information provided
Selective reporting (reporting bias)	High risk	Not all outcomes reported as outlined in the methods section of the trial publication. Primary outcome listed as DFS in 2005 full‐text article but reported as TTR in the 2009 abstract, and data related to overall survival not reported (although listed as a secondary outcome measure)
Other bias	Low risk	Quote: "the patients' characteristics were well balanced between the two treatment groups"