title: Axillary dissection versus no axillary dissection in patients with sentinel-node micrometastases (IBCSG 23-01): a phase 3 randomised controlled trial.
abstract: BACKGROUND
  For patients with breast cancer and metastases in the sentinel nodes, axillary dissection has been standard treatment. However, for patients with limited sentinel-node involvement, axillary dissection might be overtreatment. We designed IBCSG trial 23-01 to determine whether no axillary dissection was non-inferior to axillary dissection in patients with one or more micrometastatic (≤2 mm) sentinel nodes and tumour of maximum 5 cm.
  
  
  METHODS
  In this multicentre, randomised, non-inferiority, phase 3 trial, patients were eligible if they had clinically non-palpable axillary lymph node(s) and a primary tumour of 5 cm or less and who, after sentinel-node biopsy, had one or more micrometastatic (≤2 mm) sentinel lymph nodes with no extracapsular extension. Patients were randomly assigned (in a 1:1 ratio) to either undergo axillary dissection or not to undergo axillary dissection. Randomisation was stratified by centre and menopausal status. Treatment assignment was not masked. The primary endpoint was disease-free survival. Non-inferiority was defined as a hazard ratio (HR) of less than 1·25 for no axillary dissection versus axillary dissection. The analysis was by intention to treat. Per protocol, disease and survival information continues to be collected yearly. This trial is registered with ClinicalTrials.gov, NCT00072293.
  
  
  RESULTS
  Between April 1, 2001, and Feb 28, 2010, 465 patients were randomly assigned to axillary dissection and 469 to no axillary dissection. After the exclusion of three patients, 464 patients were in the axillary dissection group and 467 patients were in the no axillary dissection group. After a median follow-up of 5·0 (IQR 3·6-7·3) years, we recorded 69 disease-free survival events in the axillary dissection group and 55 events in the no axillary dissection group. Breast-cancer-related events were recorded in 48 patients in the axillary dissection group and 47 in the no axillary dissection group (ten local recurrences in the axillary dissection group and eight in the no axillary dissection group; three and nine contralateral breast cancers; one and five [corrected] regional recurrences; and 34 and 25 distant relapses). Other non-breast cancer events were recorded in 21 patients in the axillary dissection group and eight in the no axillary dissection group (20 and six second non-breast malignancies; and one and two deaths not due to a cancer event). 5-year disease-free survival was 87·8% (95% CI 84·4-91·2) in the group without axillary dissection and 84·4% (80·7-88·1) in the group with axillary dissection (log-rank p=0·16; HR for no axillary dissection vs axillary dissection was 0·78, 95% CI 0·55-1·11, non-inferiority p=0·0042). Patients with reported long-term surgical events (grade 3-4) included one sensory neuropathy (grade 3), three lymphoedema (two grade 3 and one grade 4), and three motor neuropathy (grade 3), all in the group that underwent axillary dissection, and one grade 3 motor neuropathy in the group without axillary dissection. One serious adverse event was reported, a postoperative infection in the axilla in the group with axillary dissection.
  
  
  CONCLUSIONS
  Axillary dissection could be avoided in patients with early breast cancer and limited sentinel-node involvement, thus eliminating complications of axillary surgery with no adverse effect on survival.
  
  
  BACKGROUND
  None.
authors.affiliation: Molecular Senology Unit, Senology Division, European Institute of Oncology, Milan, Italy. viviana.galimberti@ieo.it
authors.forename: Viviana
authors.initials: V
authors.lastname: Galimberti
authors.forename: Bernard F
authors.initials: BF
authors.lastname: Cole
authors.forename: Stefano
authors.initials: S
authors.lastname: Zurrida
authors.forename: Giuseppe
authors.initials: G
authors.lastname: Viale
authors.forename: Alberto
authors.initials: A
authors.lastname: Luini
authors.forename: Paolo
authors.initials: P
authors.lastname: Veronesi
authors.forename: Paola
authors.initials: P
authors.lastname: Baratella
authors.forename: Camelia
authors.initials: C
authors.lastname: Chifu
authors.forename: Manuela
authors.initials: M
authors.lastname: Sargenti
authors.forename: Mattia
authors.initials: M
authors.lastname: Intra
authors.forename: Oreste
authors.initials: O
authors.lastname: Gentilini
authors.forename: Mauro G
authors.initials: MG
authors.lastname: Mastropasqua
authors.forename: Giovanni
authors.initials: G
authors.lastname: Mazzarol
authors.forename: Samuele
authors.initials: S
authors.lastname: Massarut
authors.forename: Jean-Rémi
authors.initials: JR
authors.lastname: Garbay
authors.forename: Janez
authors.initials: J
authors.lastname: Zgajnar
authors.forename: Hanne
authors.initials: H
authors.lastname: Galatius
authors.forename: Angelo
authors.initials: A
authors.lastname: Recalcati
authors.forename: David
authors.initials: D
authors.lastname: Littlejohn
authors.forename: Monika
authors.initials: M
authors.lastname: Bamert
authors.forename: Marco
authors.initials: M
authors.lastname: Colleoni
authors.forename: Karen N
authors.initials: KN
authors.lastname: Price
authors.forename: Meredith M
authors.initials: MM
authors.lastname: Regan
authors.forename: Aron
authors.initials: A
authors.lastname: Goldhirsch
authors.forename: Alan S
authors.initials: AS
authors.lastname: Coates
authors.forename: Richard D
authors.initials: RD
authors.lastname: Gelber
authors.forename: Umberto
authors.initials: U
authors.lastname: Veronesi
mesh_terms: D000328:Adult; D000368:Aged; D001365:Axilla; D001943:Breast Neoplasms / Q000473:pathology* / Q000503:physiopathology / Q000601:surgery*; D018572:Disease-Free Survival; D005260:Female; D005500:Follow-Up Studies; D006801:Humans; D008198:Lymph Nodes / Q000473:pathology / Q000601:surgery*; D008207:Lymphatic Metastasis; D008875:Middle Aged; D060787:Neoplasm Grading; D061206:Neoplasm Micrometastasis; D021701:Sentinel Lymph Node Biopsy; D016896:Treatment Outcome