title: Association of occult metastases in sentinel lymph nodes and bone marrow with survival among women with early-stage invasive breast cancer.
abstract: BACKGROUND
  Immunochemical staining of sentinel lymph nodes (SLNs) and bone marrow identifies breast cancer metastases not seen with routine pathological or clinical examination.
  
  
  OBJECTIVE
  To determine the association between survival and metastases detected by immunochemical staining of SLNs and bone marrow specimens from patients with early-stage breast cancer.
  
  
  METHODS
  From May 1999 to May 2003, 126 sites in the American College of Surgeons Oncology Group Z0010 trial enrolled women with clinical T1 to T2N0M0 invasive breast carcinoma in a prospective observational study.
  
  
  METHODS
  All 5210 patients underwent breast-conserving surgery and SLN dissection. Bone marrow aspiration at the time of operation was initially optional and subsequently mandatory (March 2001). Sentinel lymph node specimens (hematoxylin-eosin negative) and bone marrow specimens were sent to a central laboratory for immunochemical staining; treating clinicians were blinded to results.
  
  
  METHODS
  Overall survival (primary end point) and disease-free survival (a secondary end point).
  
  
  RESULTS
  Of 5119 SLN specimens (98.3%), 3904 (76.3%) were tumor-negative by hematoxylin-eosin staining. Of 3326 SLN specimens examined by immunohistochemistry, 349 (10.5%) were positive for tumor. Of 3413 bone marrow specimens examined by immunocytochemistry, 104 (3.0%) were positive for tumors. At a median follow-up of 6.3 years (through April 2010), 435 patients had died and 376 had disease recurrence. Immunohistochemical evidence of SLN metastases was not significantly associated with overall survival (5-year rates: 95.7%; 95% confidence interval [CI], 95.0%-96.5% for immunohistochemical negative and 95.1%; 95% CI, 92.7%-97.5% for immunohistochemical positive disease; P = .64; unadjusted hazard ratio [HR], 0.90; 95% CI, 0.59-1.39; P = .64). Bone marrow metastases were associated with decreased overall survival (unadjusted HR for mortality, 1.94; 95% CI, 1.02-3.67; P = .04), but neither immunohistochemical evidence of tumor in SLNs (adjusted HR, 0.88; 95% CI, 0.45-1.71; P = .70) nor immunocytochemical evidence of tumor in bone marrow (adjusted HR, 1.83; 95% CI, 0.79-4.26; P = .15) was statistically significant on multivariable analysis.
  
  
  CONCLUSIONS
  Among women receiving breast-conserving therapy and SLN dissection, immunohistochemical evidence of SLN metastasis was not associated with overall survival over a median of 6.3 years, whereas occult bone marrow metastasis, although rare, was associated with decreased survival.
  
  
  BACKGROUND
  clinicaltrials.gov Identifier: NCT00003854.
authors.affiliation: Division of Surgical Oncology, John Wayne Cancer Institute at Saint John's Health Center, Santa Monica, California, USA. armando.giuliano@cshs.org
authors.forename: Armando E
authors.initials: AE
authors.lastname: Giuliano
authors.forename: Debra
authors.initials: D
authors.lastname: Hawes
authors.forename: Karla V
authors.initials: KV
authors.lastname: Ballman
authors.forename: Pat W
authors.initials: PW
authors.lastname: Whitworth
authors.forename: Peter W
authors.initials: PW
authors.lastname: Blumencranz
authors.forename: Douglas S
authors.initials: DS
authors.lastname: Reintgen
authors.forename: Monica
authors.initials: M
authors.lastname: Morrow
authors.forename: A Marilyn
authors.initials: AM
authors.lastname: Leitch
authors.forename: Kelly K
authors.initials: KK
authors.lastname: Hunt
authors.forename: Linda M
authors.initials: LM
authors.lastname: McCall
authors.forename: Andrea
authors.initials: A
authors.lastname: Abati
authors.forename: Richard
authors.initials: R
authors.lastname: Cote
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D001706:Biopsy; D001853:Bone Marrow / Q000473:pathology; D019046:Bone Marrow Neoplasms / Q000175:diagnosis / Q000556:secondary*; D001943:Breast Neoplasms / Q000401:mortality* / Q000473:pathology* / Q000601:surgery; D002277:Carcinoma / Q000401:mortality* / Q000473:pathology* / Q000601:surgery; D018572:Disease-Free Survival; D005260:Female; D006801:Humans; D007150:Immunohistochemistry; D008207:Lymphatic Metastasis; D015412:Mastectomy, Segmental; D008875:Middle Aged; D009361:Neoplasm Invasiveness; D011446:Prospective Studies; D021701:Sentinel Lymph Node Biopsy