title: Long-term follow-up study of a prospective multicenter sentinel node trial: molecular detection of breast cancer sentinel node metastases.
abstract: BACKGROUND
  This prospective multicenter sentinel lymph node (SLN) trial investigated whether molecular analysis would improve the detection of SLN metastases and their prognostic value. We report mammaglobin quantitative real-time polymerase chain reaction (qRT-PCR) results and clinical outcome for 547 patients (mean follow-up 7 years).
  
  
  METHODS
  Breast cancer patients (excluding stage IV disease or palpable nodes) were enrolled from 1996 to 2005 at 16 institutional review board-approved sites. Alternate 2-mm serial sections of each SLN were examined by hematoxylin and eosin staining with or without immunohistochemistry at multiple levels or blinded and assayed by Taqman qRT-PCR according to previously established thresholds.
  
  
  RESULTS
  Mammaglobin remains a highly specific (99%), sensitive (97% primary tumor; 82% N1 SLN) marker for breast cancer. Mammaglobin SLN expression was associated with other prognostic factors, was detected in most patients with distant recurrence (48 of 79; 61%), and was associated with decreased recurrence-free survival (log rank P < 0.0001). Molecular analysis upstaged 13% (52 of 394) node-negative (N0) patients who exhibited a significantly lower distant recurrence-free survival compared to node-negative, PCR-negative patients (80 vs. 91%; P < 0.04). N0 patients with PCR-positive SLN were 3.4 times more likely to experience relapse than PCR-negative patients (odds ratio 3.4; 95% confidence interval 1.6-7.1; P = 0.001). However, molecular staging failed to predict most of the N0 patient recurrences (25 of 34) and was not a statistically significant independent predictor of distant recurrence.
  
  
  CONCLUSIONS
  To our knowledge, these data are the first to prospectively compare PCR detection of SLN metastases with long-term outcome in breast cancer patients. Molecular staging of SLN detected clinically significant disease missed by standard pathology. Further refinement and optimization of molecular staging is indicated to improve clinical utility.
authors.affiliation: Department of Surgery, The Brody School of Medicine at East Carolina University, Greenville, NC, USA. verbanack@ecu.edu
authors.forename: Kathryn Mary
authors.initials: KM
authors.lastname: Verbanac
authors.forename: Christopher Justus
authors.initials: CJ
authors.lastname: Min
authors.forename: Ann Elizabeth
authors.initials: AE
authors.lastname: Mannie
authors.forename: Jianfen
authors.initials: J
authors.lastname: Lu
authors.forename: Kevin F
authors.initials: KF
authors.lastname: O'Brien
authors.forename: Martin
authors.initials: M
authors.lastname: Rosman
authors.forename: Lorraine
authors.initials: L
authors.lastname: Tafra
mesh_terms: D001365:Axilla; D001943:Breast Neoplasms / Q000175:diagnosis* / Q000235:genetics / Q000378:metabolism; D018270:Carcinoma, Ductal, Breast / Q000175:diagnosis* / Q000235:genetics / Q000378:metabolism; D002285:Carcinoma, Intraductal, Noninfiltrating / Q000175:diagnosis* / Q000235:genetics / Q000378:metabolism; D018275:Carcinoma, Lobular / Q000175:diagnosis* / Q000235:genetics / Q000378:metabolism; D005260:Female; D005500:Follow-Up Studies; D006801:Humans; D007124:Immunoenzyme Techniques; D008207:Lymphatic Metastasis; D060785:Mammaglobin A; D008875:Middle Aged; D009361:Neoplasm Invasiveness; D009363:Neoplasm Proteins / Q000235:genetics* / Q000378:metabolism; D009364:Neoplasm Recurrence, Local / Q000175:diagnosis* / Q000235:genetics / Q000378:metabolism; D009367:Neoplasm Staging; D011379:Prognosis; D011446:Prospective Studies; D012333:RNA, Messenger / Q000235:genetics; D020133:Reverse Transcriptase Polymerase Chain Reaction; D021701:Sentinel Lymph Node Biopsy; D013997:Time Factors; D014598:Uteroglobin / Q000235:genetics* / Q000378:metabolism
chemical_list: D060785:Mammaglobin A; D009363:Neoplasm Proteins; D012333:RNA, Messenger; C556448:SCGB2A2 protein, human; D014598:Uteroglobin