Alamgeer 2014.

Methods	Accrual: April 2004 to December 2011 Open‐label, phase III randomised controlled trial conducted in Australia Neoadjuvant therapy Multicentre study Follow‐up: not reported
Participants	Age: < 50 years: 56%; ≥ 50 years: 44% T stage: 18% T1, 65% T2, 17% T3 Locally advanced breast cancer Lymph node‐positive: 81% HER2‐positive: 24% Triple‐negative: 24% Luminal A: 20%; luminal B: 41%
Interventions	Arm 1 ('arm B' in the trial publication): docetaxel (100 mg/m²) every 3 weeks for 4 cycles followed by fluorouracil (500 mg/m²), epirubicin (100 mg/m²), cyclophosphamide (500 mg/m²) every 3 weeks for 4 cycles Arm 2 ('arm A' in the trial publication): fluorouracil (500 mg/m²), epirubicin (100 mg/m²), cyclophosphamide (500 mg/m²) every 3 weeks for 4 cycles followed by docetaxel (100 mg/m²) every 3 weeks for 4 cycles
Outcomes	Primary outcome Identification of markers that correlate with tumour response to chemotherapy Secondary outcomes DFS (collected but not reported) OS
Notes	Clinical trial registration number: ACTRN12605000588695 Funding considerations: ANZCTR record states: primary sponsor – Monash Health; secondary sponsor: Sanofi Aventis; trial publication states support from Victorian Cancer Agency. Trialist was contacted in July 2018 for survival data based on sequencing; as of 16 August 2018, no reply received.
Risk of bias
Bias	Authors' judgement	Support for judgement
Random sequence generation (selection bias)	Low risk	From trial registry record: random sequence generated through "coin toss with no restriction."
Allocation concealment (selection bias)	Unclear risk	No details provided
Blinding of participants and personnel (performance bias) All outcomes	Low risk	Open‐label study. Participants in both groups received the same drugs though in different order. Therefore, it was judged unlikely that this would lead to a material bias in participants' and physicians' behaviours even when unblinded.
Blinding of outcome assessment (detection bias) Overall survival	Low risk	Lack of blinding unlikely to influence this outcome
Blinding of outcome assessment (detection bias) DFS	Low risk	Lack of blinding unlikely to have an impact on outcome assessment for this review question where trial participants received both treatment regimens
Blinding of outcome assessment (detection bias) Neoadjuvant studies only: pCR	Low risk	Assessments including mammography, ultrasound, etc were repeated before chemotherapy commenced and repeated after 4 cycles of chemotherapy; plus periodic clinical assessments after each cycle of chemotherapy to ensure tumour was not progressing. pCR was viewed to be an objective outcome and a review by a pathologist on whether pCR had been achieved or not was unlikely to be influenced by unblinding.
Incomplete outcome data (attrition bias) All outcomes	Low risk	Although a CONSORT diagram was not provided, it appeared that there were no missing data for the 2 outcomes reported.
Selective reporting (reporting bias)	Low risk	Prespecified outcomes in ACTRN record included DFS; data for this outcome were not reported in the trial publication. The publication added a new important outcome – pCR – that was not in the trial record but this was considered an important outcome to report in the publication.
Other bias	Low risk	None identified