Boccardo.

Methods	Randomised controlled trial Multi‐centre, international, open‐label Central randomisation by random numbers tables Accrual April 1997 to January 2004 Baseline patient and tumour characteristics well balanced excluding tumour size
Participants	Female, premenopausal and postmenopausal Aged 18 to 70 years. Median age not reported Operable, unilateral breast cancer, completely resected with clear surgical margins Axillary node positive: 100% (3 or more lymph nodes) Exclusion of metastatic disease HR positive: ER positive: 89% to 90% in each treatment arm
Interventions	ARM 1 (E‐CMF) E × 4 21‐day cycles (epirubicin 100 mg/m²) followed by CMF × 4 28‐day cycles (cyclophosphamide 600 mg/m², methotrexate 40 mg/m², fluorouracil 600 mg/m²) ARM 2 (Paclitaxel‐EV) Paclitaxel × 4 21‐day cycles (paclitaxel 175 mg/m²) followed by EV × 4 21‐day cycles (epirubicin 75 mg/m², vinorelbine 25 mg/m²) Tamoxifen 20 mg/d for 5 years given to all patients who were ER and/or PR positive Radiotherapy given as mandatory following breast‐conserving surgery, and used after mastectomy according to local guidelines
Outcomes	Primary endpoint: Overall survival Secondary endpoints: Relapse‐free survival Toxicity
Notes	Median follow‐up: 102 months No trial record identified Funding: National Research Council and University of Research Italian Minister In the review update, O‐E and V for OS and DFS derived using Method 3 (Tierney 2007)
Risk of bias
Bias	Authors' judgement	Support for judgement
Random sequence generation (selection bias)	Low risk	Quote: "randomization... was based on random number tables"
Allocation concealment (selection bias)	Low risk	Central allocation Quote: "randomization was carried out by telephone from a central office of the coordinating center"
Blinding of participants and personnel (performance bias) All outcomes	Unclear risk	Open‐label
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	Clinical examinations every 3 months for 2 years, every 6 months for years 3 to 5, and annually thereafter. Chest X‐ray, liver ultrasound, and/or CT abdomen and a bone scan repeated annually during first 5 years of follow‐up. CBC and biochemistry repeated before each chemotherapy cycle. Toxicity scored using WHO criteria Comment: no involvement of an independent adjudication committee for outcome assessment
Incomplete outcome data (attrition bias) All outcomes	Low risk	All 244 patients randomised accounted for in results (122 per treatment arm)
Selective reporting (reporting bias)	Low risk	All outcomes reported in the methods section included in the results section of the trial publication. No trial registry record or protocol found
Other bias	Unclear risk	Quote: "treatment arms were well balanced with respect to major pretreatment variables, excluding tumour size (more patients in the E‐CMF arm were affected by tumours < 2 cm in size, P = 0.01)"