Addenbrookes.

Methods	Study design: RCT Country: UK Study period: 1958‐1965 Inclusion criteria: clinical stage II breast cancer (a tumour of any size but confined to the breast tissue with mobile axillary nodes present on the same side, no skin infiltration or muscle involvement) and judged by the surgeon to be suitable for treatment allocation including postoperative radiotherapy Exclusion criteria: none listed, but some patients were excluded owing to age, poor general condition or the surgeon’s opinion that their tumour was unsuitable for treatments provided in the trial Length of follow up: 5‐12 years
Participants	No. in trial arms: simple: N = 113; ALND: N = 91 Age: simple: mean = 54 years; ALND: mean = 54 years Stage distribution: stage II (entry requirement) Proportion node positive: simple: 47/113 (42/113 were negative and 24/113 were nil – no node histopathology – possibly because no nodes were removed); ALND: 51/91 (39/91 were negative and 1/91 was nil – no node histopathology) Pathological type of breast cancer: not reported
Interventions	Modified simple mastectomy (removal of breast tissue without removal of the pectoral muscle. This might include removal of accessible axillary glands with no block dissection of the axilla) + x‐ray therapy vs radical mastectomy (removal of breast tissue and sternal head of the pectoralis‐major muscle and the pectoralis‐minor muscle, together with block dissection of the axilla. The surgeon might remove the internal mammary nodes if he wished) + x‐ray therapy
Outcomes	Survival, recurrence‐free survival, oedema of the arm, shoulder stiffness, skin graft, delayed healing
Axillary node surgery	Minimum no. nodes to be removed according to protocol: no minimum for the simple mastectomy arm – accessible nodes were optionally removed, and some participants had no nodes removed for histopathology Nodes removed radical mastectomy arm: not reported Nodes removed simple mastectomy arm: not reported Method of node pathological analysis: not reported Further treatment for node‐positive cases: no
Radiotherapy	Both arms: X‐ray therapy was administered as soon after surgery as possible, typically within 3‐4 weeks. Two 30 × 10 cm longitudinal fields were used to treat the whole pectoral area, axilla and supraclavicular and internal‐mammary‐node regions in a single block. Bolus was used and a minimum tumour dose of 3250r was given, during an overall time of 18 days, by means of 250 kV rays of h.v.l. 2.7 mm Cu. If wide separation of the fields was necessary, an extra direct field was used to build up the dose centrally and over the supraclavicular area RT same in all trial arms? yes
Hormone and chemotherapy	Both arms: no details reported
Notes	N = ≥ 3 ALND patients had tumours > 5 cm in diameter (i.e. stage III by the 1961 international scheme of clinical staging). Baseline differences? ALND group included a larger proportion with inner quadrant tumours. Intention to treat analyses? No details were provided, and for long‐term adverse events, data are missing from N = 106
Risk of bias
Bias	Authors' judgement	Support for judgement
Random sequence generation (selection bias)	Low risk	Once entered into the trial, the drawing of an odd or even number from a random number table decided the type of treatment. This procedure was performed by personnel who were not in any way concerned with clinical examination or treatment of participants.
Allocation concealment (selection bias)	Low risk	See cell above.
Blinding of outcome assessment (detection bias) Disease control in the axilla	Unclear risk	Outcome was not reported.
Blinding of outcome assessment (detection bias) Breast cancer recurrence	Unclear risk	No details were provided. Outcome might have been affected by blinding.
Blinding of outcome assessment (detection bias) Short term adverse events	Unclear risk	No details were provided. Outcome might have been affected by blinding.
Blinding of outcome assessment (detection bias) Long term adverse events	Unclear risk	No details were provided. Outcome might have been affected by blinding.
Incomplete outcome data (attrition bias) Survival	Unclear risk	Patients entered into the trial were not reported in Brinkley et al (1966) – only those who received treatment were reported.
Incomplete outcome data (attrition bias) Axillary recurrence	Unclear risk	Outcome was not reported.
Incomplete outcome data (attrition bias) Breast cancer recurrence	Unclear risk	Patients entered into the trial were not reported in Brinkley et al (1966) – only those who received treatment were reported.
Incomplete outcome data (attrition bias) Short term adverse events	Unclear risk	Patients entered into the trial were not reported in Brinkley et al (1966) – only those who received treatment were reported.
Incomplete outcome data (attrition bias) Long term adverse events	Unclear risk	Patients entered into the trial were not reported in Brinkley et al (1966) – only those who received treatment were reported. In the 1971 paper, results were reported for 98/114 participants who were still alive.
Selective reporting (reporting bias)	Low risk	Major outcomes were reported.