Genoa.

Methods	Study design: RCT, non‐inferiority Country: Italy Study period: 1998‐2001 Inclusion criteria: 18‐75 years, primary invasive breast cancer as revealed by mammography and cytohistology, clinically negative axillary lymph nodes, unifocal tumour ≤ 3 cm as estimated by echography Exclusion criteria: previous surgery on the same breast or on the ipsilateral axilla, chronic life‐threatening disease possibly preventing adjuvant therapy Length of follow‐up: event‐free survival: median = 5.5 ± 1.4 years. Overall survival: median = 5.6 ± 1.3 years
Participants	No. in trial arms: SLNB: N = 110; ALND: N = 115 Age: SLNB: median (range) = 60 (35‐75) years; ALND: median (range) = 59 (28‐75) years Stage distribution: SLNB: pTis N = 1, pT1mic N = 2, pT1a N = 11, pT1b N = 24, pT1c N = 59, pT2 N = 13; pN0 N = 77, pN1mic N = 5, pN1a N = 21, pN2a N = 6, pN3a N = 1. ALND: pTis N = 1, pT1mic N = 0, pT1a N = 10, pT1b N = 18, pT1c N = 57, pT2 N = 29; pN0 N = 79, pN1mic N = 11, pN1a N = 17, pN2a N = 5, pN3a N = 3 Proportion node positive: SLNB: N = 33/110; ALND: N = 36/115 Pathological type of breast cancer: SLNB: ductal NOS, N = 107; lobular, N = 1; in situ, N = 1; other, N = 1. ALND: ductal NOS, N = 110; lobular, N = 2; in situ, N = 1; other, N = 2
Interventions	Breast surgery (mastectomy or conservative quadrantectomy carried out according to standard criteria) + sentinel lymph node biopsy (SLNB; identified by breast lymphoscintigraphy and lymphatic dye mapping) + axillary lymph node dissection (ALND) vs breast surgery + SLNB + ALND only if SLN was found to be positive at the intraoperative evaluation. Any participant whose SLNs could not be identified received ALND independently of the treatment assigned.
Outcomes	5‐Year event‐free survival and 5‐year overall survival, axillary recurrence in those who did not undergo axillary lymph node dissection, sensitivity and predictive value of SLNB in ALND arm
Axillary node surgery	Minimum no. nodes to be removed according to protocol: not reported Nodes removed clearance arm: N = 211, mean = 1.83 per participant Nodes removed SNB + clearance: N = 194, mean 1.76 per participant Method of node pathological analysis: SLN bisected on major axis, and 5 pairs of frozen sections, each 4 μm thick, were cut every 10 μm in each half of the node. The first, third and fifth sections were stained with hematoxylin‐eosin. If negative, then second and fourth sections were tested with immunohistochemistry for cytokeratins, via cytokeratin mAb and horseradish peroxidase. Remaining tissue was embedded in paraffin for postoperative evaluation. Further treatment for node‐positive cases: yes (ALND and/or adjuvant therapy)
Radiotherapy	ALND or SLNB: Only participants who received conservative surgery were given radiotherapy (50 Gy/8 wk) to the ipsilateral breast. No RT was given to the axilla. RT same in all trial arms? yes
Hormone and chemotherapy	Both arms: The choice of adjuvant chemotherapy and/or hormone therapy regimen, when given, was based on the main prognostic factors of the primary tumour (nodal status, tumour size, tumour grading, hormonal receptor status).
Notes	No SLN was found in 3 patients who had ALND (1 control/2 research). Study was powered for 2570 participants; only 248 were recruited, and the trial was interrupted when participants became aware of promising SLNB procedure and refused randomisation to ALND. Baseline differences? No statistically significant differences between groups were noted at baseline. Intention‐to‐treat analyses? Paper stated that intention‐to‐treat analyses were employed.
Risk of bias
Bias	Authors' judgement	Support for judgement
Random sequence generation (selection bias)	Low risk	Computer‐generated randomisation list was used.
Allocation concealment (selection bias)	Low risk	Central allocation was conducted by the Epidemiology and Clinical Trials Unit of the Institute.
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	Outcome was not reported.
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	Outcome was not reported.
Selective reporting (reporting bias)	Unclear risk	Short‐term and long‐term adverse events were not reported.