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: clinicaltrials.gov Identifier: NCT00003854.
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: clinicaltrials.gov Identifier: NCT00003854.
Authors: I J Diel; M Kaufmann; S D Costa; R Holle; G von Minckwitz; E F Solomayer; S Kaul; G Bastert Journal: J Natl Cancer Inst Date: 1996-11-20 Impact factor: 13.506
Authors: Henry K Lin; Siyang Zheng; Anthony J Williams; Marija Balic; Susan Groshen; Howard I Scher; Martin Fleisher; Walter Stadler; Ram H Datar; Yu-Chong Tai; Richard J Cote Journal: Clin Cancer Res Date: 2010-09-28 Impact factor: 12.531
Authors: A Molino; M Colombatti; F Bonetti; M Zardini; F Pasini; A Perini; G Pelosi; G Tridente; D Veneri; G L Cetto Journal: Cancer Date: 1991-02-15 Impact factor: 6.860
Authors: Marija Balic; Henry Lin; Lillian Young; Debra Hawes; Armando Giuliano; George McNamara; Ram H Datar; Richard J Cote Journal: Clin Cancer Res Date: 2006-10-01 Impact factor: 12.531
Authors: Donald L Weaver; Takamaru Ashikaga; David N Krag; Joan M Skelly; Stewart J Anderson; Seth P Harlow; Thomas B Julian; Eleftherios P Mamounas; Norman Wolmark Journal: N Engl J Med Date: 2011-01-19 Impact factor: 91.245
Authors: Maaike de Boer; Carolien H M van Deurzen; Jos A A M van Dijck; George F Borm; Paul J van Diest; Eddy M M Adang; Johan W R Nortier; Emiel J T Rutgers; Caroline Seynaeve; Marian B E Menke-Pluymers; Peter Bult; Vivianne C G Tjan-Heijnen Journal: N Engl J Med Date: 2009-08-13 Impact factor: 91.245
Authors: Laura S Dominici; Monica Morrow; Elizabeth Mittendorf; Jennifer Bellon; Tari A King Journal: Curr Probl Surg Date: 2016-11-29 Impact factor: 1.909
Authors: Elizabeth A Mittendorf; Karla V Ballman; Linda M McCall; Min Yi; Aysegul A Sahin; Isabelle Bedrosian; Nora Hansen; Sheryl Gabram; Thelma Hurd; Armando E Giuliano; Kelly K Hunt Journal: J Clin Oncol Date: 2014-12-08 Impact factor: 44.544
Authors: S P Somashekhar; Zahoor Ahmed Naikoo; Shabber S Zaveri; Soumya Holla; Suresh Chandra; Suniti Mishra; R V Parameswaran Journal: Indian J Surg Date: 2013-02-05 Impact factor: 0.656