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

Armando E. Giuliano, Debra Hawes, Karla V. Ballman, Pat W. Whitworth, Peter W. Blumencranz, Douglas S. Reintgen, Monica Morrow, A. Marilyn Leitch, Kelly K. Hunt, Linda M. McCall, Andrea Abati, Richard Cote

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Abstract

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 (hematoxylineosin 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: clinicaltrials.gov Identifier: NCT00003854.

Original languageEnglish (US)
Pages (from-to)385-393
Number of pages9
JournalJAMA - Journal of the American Medical Association
Volume306
Issue number4
DOIs
StatePublished - Jul 27 2011

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Bone Marrow
Breast Neoplasms
Neoplasm Metastasis
Survival
Confidence Intervals
Staining and Labeling
Neoplasms
Lymph Node Excision
Immunohistochemistry
Sentinel Lymph Node
Segmental Mastectomy
Hematoxylin
Eosine Yellowish-(YS)
Disease-Free Survival
Observational Studies
Breast
Outcome Assessment (Health Care)
Prospective Studies
Recurrence
Mortality

ASJC Scopus subject areas

  • Medicine(all)

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Association of occult metastases in sentinel lymph nodes and bone marrow with survival among women with early-stage invasive breast cancer. / Giuliano, Armando E.; Hawes, Debra; Ballman, Karla V.; Whitworth, Pat W.; Blumencranz, Peter W.; Reintgen, Douglas S.; Morrow, Monica; Leitch, A. Marilyn; Hunt, Kelly K.; McCall, Linda M.; Abati, Andrea; Cote, Richard.

In: JAMA - Journal of the American Medical Association, Vol. 306, No. 4, 27.07.2011, p. 385-393.

Research output: Contribution to journalArticle

Giuliano, AE, Hawes, D, Ballman, KV, Whitworth, PW, Blumencranz, PW, Reintgen, DS, Morrow, M, Leitch, AM, Hunt, KK, McCall, LM, Abati, A & Cote, R 2011, 'Association of occult metastases in sentinel lymph nodes and bone marrow with survival among women with early-stage invasive breast cancer', JAMA - Journal of the American Medical Association, vol. 306, no. 4, pp. 385-393. https://doi.org/10.1001/jama.2011.1034
Giuliano, Armando E. ; Hawes, Debra ; Ballman, Karla V. ; Whitworth, Pat W. ; Blumencranz, Peter W. ; Reintgen, Douglas S. ; Morrow, Monica ; Leitch, A. Marilyn ; Hunt, Kelly K. ; McCall, Linda M. ; Abati, Andrea ; Cote, Richard. / Association of occult metastases in sentinel lymph nodes and bone marrow with survival among women with early-stage invasive breast cancer. In: JAMA - Journal of the American Medical Association. 2011 ; Vol. 306, No. 4. pp. 385-393.
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abstract = "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 (hematoxylineosin 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: clinicaltrials.gov Identifier: NCT00003854.",
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T1 - Association of occult metastases in sentinel lymph nodes and bone marrow with survival among women with early-stage invasive breast cancer

AU - Giuliano, Armando E.

AU - Hawes, Debra

AU - Ballman, Karla V.

AU - Whitworth, Pat W.

AU - Blumencranz, Peter W.

AU - Reintgen, Douglas S.

AU - Morrow, Monica

AU - Leitch, A. Marilyn

AU - Hunt, Kelly K.

AU - McCall, Linda M.

AU - Abati, Andrea

AU - Cote, Richard

PY - 2011/7/27

Y1 - 2011/7/27

N2 - 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 (hematoxylineosin 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: clinicaltrials.gov Identifier: NCT00003854.

AB - 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 (hematoxylineosin 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: clinicaltrials.gov Identifier: NCT00003854.

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