NSABP B‐28.

Methods	Randomised controlled trial Multi‐centre Central randomisation, stratified for number of positive nodes, type of surgery, and tamoxifen use Accrual August 1995 to May 1998 Baseline patient and tumour characteristics well balanced between treatment arms
Participants	Female, premenopausal and postmenopausal Operable breast cancer with free surgical margins Axillary node positive: 100% HR positive: 66% in each treatment arm Exclusion of metastatic disease
Interventions	ARM 1 (AC): AC × 4 21‐day cycles (doxorubicin 60 mg/m², cyclophosphamide 600 mg/m²) ARM 2 (AC‐T): AC × 4 21‐day cycles (as per control arm) followed by T × 4 21‐day cycles (paclitaxel 225 mg/m²) Tamoxifen 20 mg/d for 5 years given to all patients over 50 years and to those younger than 50 years with ER and/or PR positive Whole‐breast irradiation given to patients treated with breast‐conserving surgery
Outcomes	Primary endpoints: Disease‐free survival Overall survival Secondary endpoints: Toxicity Post‐hoc analyses presented in 2005 publication but not part of the trial protocol (as described in the publication): Treatment effectiveness in hormone receptor positive vs hormone receptor negative Recurrence‐free survival
Notes	Intention‐to‐treat analysis Median follow‐up: 64.6 months 79% continuing follow‐up at 5 years Trial identifier not retrieved Supported by Public Health Service grants from NCI and NIH (USA)
Risk of bias
Bias	Authors' judgement	Support for judgement
Random sequence generation (selection bias)	Low risk	Quote: "patient assignment to the two treatment arms was balanced… using a biased‐coin minimisation algorithm"
Allocation concealment (selection bias)	Low risk	Central allocation Quote: "random assignment was performed centrally" at the NSABP Biostatistical Centre in Pittsburgh, PA
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	Gynaecological exam (where applicable), chest X‐ray, and bilateral/unilateral mammogram yearly for first 5 years. Physical exam, gynaecological exam, and mammogram annually after 5‐year follow‐up. History, physical exam, and haematological studies and chemistries on day 1 before each cycle and every 6 months for first 5 years Comment: no independent adjudication committee involved in assessing these outcomes
Incomplete outcome data (attrition bias) All outcomes	Low risk	Intention‐to‐treat analysis. 79% of participants continuing follow‐up at 64.6 months. Only 1 patient contributing no follow‐up in the non‐taxane treatment arm
Selective reporting (reporting bias)	Low risk	Outcomes listed in methods and results sections of the trial publications consistent with trial listing at the NCI (cancer.gov/about‐cancer/treatment/clinical‐trials/search/)
Other bias	Low risk	Quote: "patient and tumour characteristics were distributed evenly between the two groups"