title: Tumor markers in the early detection of tumor recurrence in breast cancer patients: CA 125, CYFRA 21-1, HER2 shed antigen, LDH and CRP in combination with CEA and CA 15-3.
abstract: BACKGROUND
  Kinetics of CA 15-3 and CEA have a high specificity in the early detection of metastatic breast cancer (MBC). However, this high specificity is associated with a lack of sensitivity. To decrease the number of false negative patients, the additional diagnostic potential of an extended panel of biomarkers was evaluated.
  
  
  METHODS
  This analysis was performed as part of a large follow-up study (1998-2010) evaluating 813 patients with a median follow-up of 63months. After primary therapy, all patients underwent tumor marker monitoring for CEA and CA 15-3 at 6-week intervals. A reproducible previously defined increase (≥100%) based on the individual baseline value of each patient was considered as a strong indicator of MBC. For the present analysis, we retrospectively evaluated 1011 blood samples from 95 patients. Forty-seven of these had metastatic disease for the first time at the time of this evaluation, while the remaining 48 patients showed no evidence of disease. The sera of these patients were additionally assessed for the following parameters: cancer antigen (CA) 125, cytokeratin-19 soluble fragment (CYFRA 21-1), HER2 shed antigen, lactate-dehydrogenase (LDH) and C-reactive protein (CRP).
  
  
  RESULTS
  26 of 47 patients with MBC showed a reproducible tumor marker increase of at least CEA and/or CA 15-3 (55.3%, true-positive). The remaining 21 patients with MBC showed no increase in CEA or CA 15-3 (44.7%, false negative, FN). By combining all markers mentioned above, 41 of 47 patients with MBC showed a reproducible marker increase with a sensitivity of 87.2% and specificity of 100%.
  
  
  CONCLUSIONS
  This retrospective analysis indicates that a panel of biomarkers can increase the sensitivity of the CA 15-3/CEA combination without loss of specificity. The combined use is therefore helpful for early detection of MBC.
authors.affiliation: Department of Internal Medicine III, University Hospital Munich-Grosshadern, 81377 Munich, Germany. Electronic address: Dorit.DiGioia@med.uni-muenchen.de.
authors.forename: Dorit
authors.initials: D
authors.lastname: Di Gioia
authors.affiliation: Institute of Laboratory Medicine, University Hospital Munich-Grosshadern, 81377 Munich, Germany.
authors.forename: Irene
authors.initials: I
authors.lastname: Blankenburg
authors.affiliation: Institute of Laboratory Medicine, University Hospital Munich-Grosshadern, 81377 Munich, Germany.
authors.forename: Dorothea
authors.initials: D
authors.lastname: Nagel
authors.affiliation: Department of Internal Medicine III, University Hospital Munich-Grosshadern, 81377 Munich, Germany.
authors.forename: Volker
authors.initials: V
authors.lastname: Heinemann
authors.affiliation: Institute of Laboratory Medicine, University Hospital Munich-Grosshadern, 81377 Munich, Germany.
authors.forename: Petra
authors.initials: P
authors.lastname: Stieber
mesh_terms: D000328:Adult; D000368:Aged; D000951:Antigens, Neoplasm / Q000097:blood; D014408:Biomarkers, Tumor / Q000097:blood*; D001943:Breast Neoplasms / Q000097:blood* / Q000175:diagnosis*; D002097:C-Reactive Protein / Q000032:analysis; D018394:CA-125 Antigen / Q000097:blood; D002272:Carcinoembryonic Antigen / Q000097:blood; D055088:Early Detection of Cancer; D005260:Female; D006801:Humans; D053539:Keratin-19 / Q000097:blood; D007770:L-Lactate Dehydrogenase / Q000097:blood / Q000378:metabolism; D008875:Middle Aged; D018396:Mucin-1 / Q000097:blood; D009364:Neoplasm Recurrence, Local / Q000097:blood* / Q000175:diagnosis*; D018719:Erb-b2 Receptor Tyrosine Kinases / Q000097:blood; D012189:Retrospective Studies
chemical_list: D000951:Antigens, Neoplasm; D014408:Biomarkers, Tumor; D002097:C-Reactive Protein; D018394:CA-125 Antigen; D002272:Carcinoembryonic Antigen; D053539:Keratin-19; D007770:L-Lactate Dehydrogenase; D018396:Mucin-1; D018719:Erb-b2 Receptor Tyrosine Kinases; C102012:antigen CYFRA21.1; C508053:ERBB2 protein, human
keywords: Breast cancer; CA 125; CA 15-3; CEA; CYFRA 21-1; HER2 shed antigen; Recurrence