Edinburgh 1.

Methods	Study design: RCT Country: Scotland Study period: 1987‐1995 Inclusion criteria: < 70 years old, unilateral invasive breast cancer of clinical size ≤ 4 cm, no evidence of metastatic disease, considered suitable for either study intervention Exclusion criteria: clinically multi‐centric tumour or considered locally inoperable (T4), fixed axillary nodes (N2), history of previous invasive carcinoma at any site (except skin basal cell carcinoma) Length of follow up: median = 4.1 years
Participants	No. in trial arms: axillary clearance: N = 232; axillary sampling: N = 234 Age: axillary clearance: median = 54 years; axillary sampling: median = 54 years Stage distribution: not reported Proportion node positive: axillary clearance: N = 78/232; axillary sampling: N = 66/234 Pathological type of breast cancer: axillary clearance: no special type, N = 177; lobular, N = 11; tubular, N = 16; non‐invasive, N = 5; other, N = 23. Axillary sampling: no special type, N = 176; lobular, N = 11; tubular, N = 13; non‐invasive, N = 3; other, N = 31
Interventions	Axillary node clearance (level III) vs axillary node sampling (obtain ≥ 4 palpable lymph nodes from the axilla, starting at the axillary tail and working upwards)
Outcomes	Survival, recurrence, range of shoulder movement (6, 12, 24 and 36 months), shoulder muscle power (6, 12, 24 and 36 months), arm swelling (6, 12, 24 and 36 months)
Axillary node surgery	Minimum no. nodes to be removed according to protocol: axillary clearance: level III; axillary sampling: ≥ 4 palpable lymph nodes Nodes removed clearance arm: median (range) = 15 (4‐36) Nodes removed sampling arm: median (range) = 5 (2‐12) Method of node pathological analysis: not reported Further treatment for node‐positive cases: yes (radiotherapy)
Radiotherapy	RT node clearance arm: RT to the breast (45 Gy/20 fractions/4 wk or 45 Gy/25 fractions/5 wk for larger breasts + a boost to tumour bed by interstitial implant (20 Gy to 85% reference isodose) or electrons (15 Gy at 100% isodose/5 daily fractions/1 wk, but not to the axilla (all adjuvant)) RT node sampling arm: RT to the breast (as above) and regional lymphatics (45 Gy/20 fractions/4 wk) and to the axilla when sampling revealed involved nodes (apart from in N = 5, who were also included in another trial and did not receive RT). N = 39 with node‐negative axilla receiving RT to the axilla (all adjuvant) RT SNB arm: NA RT same in all trial arms? no
Hormone and chemotherapy	Axillary clearance: tamoxifen N = 163, chemotherapy N = 26, ovarian suppression N = 11, chemotherapy + tamoxifen N = 10, none N = 22 (all adjuvant) Axilla sampling: tamoxifen N = 174, chemotherapy N = 28, ovarian suppression N = 6, chemotherapy + tamoxifen N = 9, none N = 17 (all adjuvant)
Notes	Participants in both groups received postoperative adjuvant hormone or chemotherapy, depending on the results of pathology, including axillary node histology and oestrogen receptor status. Baseline differences? probably, but no statistical analyses compared groups at baseline Intention‐to‐treat analyses? survival, disease control in the axilla and breast cancer recurrence: stated in paper that intention‐to‐treat analyses were employed. Long‐term adverse events: stated in paper that analysis was performed per actual treatment received
Risk of bias
Bias	Authors' judgement	Support for judgement
Random sequence generation (selection bias)	Low risk	List was derived via randomised permuted blocks of 8.
Allocation concealment (selection bias)	Low risk	Central allocation was conducted by the Scottish Cancer Trials Office.
Blinding of outcome assessment (detection bias) Disease control in the axilla	Unclear risk	No details were provided.
Blinding of outcome assessment (detection bias) Breast cancer recurrence	Unclear risk	No details were provided.
Blinding of outcome assessment (detection bias) Short term adverse events	Unclear risk	Outcome was not reported.
Blinding of outcome assessment (detection bias) Long term adverse events	Unclear risk	No details were provided.
Incomplete outcome data (attrition bias) Survival	Low risk	Data appear to be available for all participants.
Incomplete outcome data (attrition bias) Axillary recurrence	Low risk	Data appear to be available for all participants.
Incomplete outcome data (attrition bias) Breast cancer recurrence	Low risk	Data appear to be available for all participants.
Incomplete outcome data (attrition bias) Short term adverse events	Unclear risk	Outcome was not reported.
Incomplete outcome data (attrition bias) Long term adverse events	Unclear risk	Data were reported for N = 126‐132 in the axillary clearance group, and for N = 114‐123 in the axilla sampling group.
Selective reporting (reporting bias)	Low risk	All major outcomes appear to have been reported apart from short‐term adverse events.