Association of occult metastases in sentinel lymph nodes and bone marrow with survival among women with early-stage invasive breast cancer

JAMA. 2011 Jul 27;306(4):385-93. doi: 10.1001/jama.2011.1034.


Context: 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.

Design, setting, and patients: 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.

Interventions: 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.

Main outcome measures: 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.

Conclusion: 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.

Trial registration: Identifier: NCT00003854.

Publication types

  • Research Support, N.I.H., Extramural

MeSH terms

  • Adult
  • Aged
  • Aged, 80 and over
  • Biopsy
  • Bone Marrow / pathology
  • Bone Marrow Neoplasms / diagnosis
  • Bone Marrow Neoplasms / secondary*
  • Breast Neoplasms / mortality*
  • Breast Neoplasms / pathology*
  • Breast Neoplasms / surgery
  • Carcinoma / mortality*
  • Carcinoma / pathology*
  • Carcinoma / surgery
  • Disease-Free Survival
  • Female
  • Humans
  • Immunohistochemistry
  • Lymphatic Metastasis*
  • Mastectomy, Segmental
  • Middle Aged
  • Neoplasm Invasiveness
  • Prospective Studies
  • Sentinel Lymph Node Biopsy*

Associated data