ELDA.

Methods	Randomised controlled trial Multi‐centre, international Central randomisation, using a minimisation procedure with centre, pT and pN category, planned number of chemotherapy cycles, age as strata Open‐label study Accrual July 2003 to April 2011 Baseline tumour characteristics well balanced although slight imbalance in distribution of comorbidities (e.g. no comorbidity in 7% and 13%, and previous cerebrovascular disease in 1% and 6% in docetaxel and CMF groups, respectively)
Participants	Female, postmenopausal Aged 65 to 79 years (median 70) Operable breast cancer with clear surgical margins Axillary node positive or high risk node negative ECOG performance status ≤ 2 HR positive: ER positive/PgR positive: 74% to 76% in each treatment group Exclusion of metastatic disease
Interventions	ARM 1 (CMF) CMF × 4 to 6 28‐day cycles (cyclophosphamide 600 mg/m², methotrexate 40 mg/m², fluorouracil 600 mg/m² on days 1 and 8) ARM 2 (Doc) Doc × 4 to 6 28‐day cycles (docetaxel 35 mg/m² on days 1, 8, and 15) 6 cycles planned for tumours < 10% positive for both ER and PgR, 4 cycles for those with ER or PR ≥ 10% Tamoxifen or aromatase inhibitors according to standard schedules given after chemotherapy to patients with tumour positive for ER/PR in at least 1% of cells Patients with HER2‐positive tumour given adjuvant trastuzumab for 1 year after chemotherapy. Radiotherapy performed when indicated after the end of chemotherapy and within 6 months after surgery
Outcomes	Primary endpoint: Disease‐free survival, defined as interval between randomisation and locoregional or distant relapse or contralateral invasive breast cancer or second primary invasive non‐breast cancer or ipsilateral or contralateral in situ ductal carcinoma or death without cancer, whichever occurred first Secondary endpoints: Toxicity, using National Cancer Institute Common Toxicity Criteria (NCI CTC) version 2.0 Compliance Quality of life, using EORTC C‐30 and BR‐23 questionnaires Overall survival
Notes	Median follow‐up 70 months (95% confidence interval 66 to 73 months) Clinical Trial Identifier: NCT00331097 (see clinicaltrials.gov/ct2/show/NCT00331097) Sponsored by the Clinical Trials Unit of the National Cancer Institute of Naples
Risk of bias
Bias	Authors' judgement	Support for judgement
Random sequence generation (selection bias)	Low risk	Quote: “randomization was carried out centrally at the Clinical Trials Unit of the NCI Naples, with a computer‐based minimization procedure…”
Allocation concealment (selection bias)	Low risk	Central randomisation Quote: “…clinicians contacted the Clinical Trials Unit by telephone or by fax”
Blinding of participants and personnel (performance bias) All outcomes	Unclear risk	Open‐label study
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	Assessment including clinical visits with biochemistry and haematological tests every 3 months for 3 years, then every 6 months for 2 years, then annually for 5 years. Chest X‐ray, ultrasonography, and mammography included. Treatment toxicity graded according to National Cancer Institute Common Toxicity Criteria Comment: no involvement of an independent adjudication committee for outcome assessment
Blinding of outcome assessment ‐ QoL (detection bias)	High risk	Patients completing EORTC QLQ‐C30a and BR23 at baseline, and at end of first, second, and third cycles of chemotherapy
Incomplete outcome data (attrition bias) All outcomes	Low risk	302 patients randomised (docetaxel: 150; CMF: 152) and 299 patients included in modified intention‐to‐treatment analysis (99.1%)
Selective reporting (reporting bias)	Low risk	Methods consistent with trial registry record (clinicaltrials.gov/ct2/show/NCT00033683). Outcomes reported in the methods and results sections of the trial publication consistent. Primary and secondary outcomes not listed at the time of registration
Other bias	Low risk	No other sources identified