title: Axillary dissection vs no axillary dissection in women with invasive breast cancer and sentinel node metastasis: a randomized clinical trial.
abstract: BACKGROUND
  Sentinel lymph node dissection (SLND) accurately identifies nodal metastasis of early breast cancer, but it is not clear whether further nodal dissection affects survival.
  
  
  OBJECTIVE
  To determine the effects of complete axillary lymph node dissection (ALND) on survival of patients with sentinel lymph node (SLN) metastasis of breast cancer.
  
  
  METHODS
  The American College of Surgeons Oncology Group Z0011 trial, a phase 3 noninferiority trial conducted at 115 sites and enrolling patients from May 1999 to December 2004. Patients were women with clinical T1-T2 invasive breast cancer, no palpable adenopathy, and 1 to 2 SLNs containing metastases identified by frozen section, touch preparation, or hematoxylin-eosin staining on permanent section. Targeted enrollment was 1900 women with final analysis after 500 deaths, but the trial closed early because mortality rate was lower than expected.
  
  
  METHODS
  All patients underwent lumpectomy and tangential whole-breast irradiation. Those with SLN metastases identified by SLND were randomized to undergo ALND or no further axillary treatment. Those randomized to ALND underwent dissection of 10 or more nodes. Systemic therapy was at the discretion of the treating physician.
  
  
  METHODS
  Overall survival was the primary end point, with a noninferiority margin of a 1-sided hazard ratio of less than 1.3 indicating that SLND alone is noninferior to ALND. Disease-free survival was a secondary end point.
  
  
  RESULTS
  Clinical and tumor characteristics were similar between 445 patients randomized to ALND and 446 randomized to SLND alone. However, the median number of nodes removed was 17 with ALND and 2 with SLND alone. At a median follow-up of 6.3 years (last follow-up, March 4, 2010), 5-year overall survival was 91.8% (95% confidence interval [CI], 89.1%-94.5%) with ALND and 92.5% (95% CI, 90.0%-95.1%) with SLND alone; 5-year disease-free survival was 82.2% (95% CI, 78.3%-86.3%) with ALND and 83.9% (95% CI, 80.2%-87.9%) with SLND alone. The hazard ratio for treatment-related overall survival was 0.79 (90% CI, 0.56-1.11) without adjustment and 0.87 (90% CI, 0.62-1.23) after adjusting for age and adjuvant therapy.
  
  
  CONCLUSIONS
  Among patients with limited SLN metastatic breast cancer treated with breast conservation and systemic therapy, the use of SLND alone compared with ALND did not result in inferior survival.
  
  
  BACKGROUND
  clinicaltrials.gov Identifier: NCT00003855.
authors.affiliation: John Wayne Cancer Institute at Saint John's Health Center, 2200 Santa Monica Blvd, Santa Monica, CA 90404, USA. giulianoa@jwci.org
authors.forename: Armando E
authors.initials: AE
authors.lastname: Giuliano
authors.forename: Kelly K
authors.initials: KK
authors.lastname: Hunt
authors.forename: Karla V
authors.initials: KV
authors.lastname: Ballman
authors.forename: Peter D
authors.initials: PD
authors.lastname: Beitsch
authors.forename: Pat W
authors.initials: PW
authors.lastname: Whitworth
authors.forename: Peter W
authors.initials: PW
authors.lastname: Blumencranz
authors.forename: A Marilyn
authors.initials: AM
authors.lastname: Leitch
authors.forename: Sukamal
authors.initials: S
authors.lastname: Saha
authors.forename: Linda M
authors.initials: LM
authors.lastname: McCall
authors.forename: Monica
authors.initials: M
authors.lastname: Morrow
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D001365:Axilla; D001943:Breast Neoplasms / Q000473:pathology / Q000532:radiotherapy / Q000601:surgery*; D018572:Disease-Free Survival; D005260:Female; D005500:Follow-Up Studies; D006801:Humans; D008197:Lymph Node Excision; D008207:Lymphatic Metastasis; D015412:Mastectomy, Segmental; D008875:Middle Aged; D009361:Neoplasm Invasiveness; D018714:Radiotherapy, Adjuvant; D021701:Sentinel Lymph Node Biopsy; D016019:Survival Analysis; D016896:Treatment Outcome