title: Serum HER2 in combination with CA 15-3 as a parameter for prognosis in patients with early breast cancer.
abstract: OBJECTIVE
  HER2 in breast cancer tissue is a marker of high prognostic and predictive relevance. Soluble HER2, the extracellular domain of the HER2/neu receptor (HER2 ECD), which is shed into the blood, has been suggested to be a helpful tumor marker. We investigated the relationship between the concentrations of HER2 ECD, CEA and CA 15-3, the association of these markers with clinicopathological features and the impact of HER2 ECD alone and in combination with known prognostic factors on disease free survival (DFS) and cancer specific survival (CSS) in untreated early breast cancer patients.
  
  
  METHODS
  HER2 ECD (ADVIA, Bayer), CEA (AxSYM, Abbott) and CA 15-3 (Elecsys, Roche) were measured at time of primary diagnosis in the pre-therapeutic (pre-operative) sera of 241 breast cancer patients and were correlated with clinicopathological parameters and outcome.
  
  
  RESULTS
  Higher HER2 ECD levels were significantly correlated with postmenopausal status (p=0.016) and tissue HER2-overexpression (p<0.0001). Higher serum levels of CA 15-3 were associated with larger tumor size (p=0.019), positive lymph nodes (p=0.019), UICC stage III (p<0.01), positive tissue HER2-overexpression (p<0.05) and negative hormone receptor status (p=0.016). In multivariate analysis, serum HER2 ECD levels, CA 15-3 levels, large tumor size and negative hormonal status were independent prognostic factors in DFS. Patients with both high levels of HER2 ECD (>15 ng/mL) and high serum levels of CA 15-3 (>24 U/mL) had the poorest prognosis with a DFS after 3 years of 50.0%. Patients without elevated serum levels had a better outcome with a DFS of 91.2%.
  
  
  CONCLUSIONS
  In our retrospective analysis, HER2 ECD and CA 15-3 were independent and better prognostic tools than HER2 in tissue. Prospective validation is necessary to confirm their usefulness in clinical practice.
authors.affiliation: Department of Internal Medicine III, Ludwig-Maximilians-University of Munich, Campus 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, Ludwig-Maximilians-University of Munich, Campus Großhadern, 81377 Munich, Germany.
authors.forename: Marie
authors.initials: M
authors.lastname: Dresse
authors.affiliation: Department of Pathology, Ludwig-Maximilians-University of Munich, 80337 Munich, Germany.
authors.forename: Doris
authors.initials: D
authors.lastname: Mayr
authors.affiliation: Institute of Laboratory Medicine, Ludwig-Maximilians-University of Munich, Campus Großhadern, 81377 Munich, Germany.
authors.forename: Dorothea
authors.initials: D
authors.lastname: Nagel
authors.affiliation: Department of Internal Medicine III, Ludwig-Maximilians-University of Munich, Campus Großhadern, 81377 Munich, Germany.
authors.forename: Volker
authors.initials: V
authors.lastname: Heinemann
authors.affiliation: Institute of Laboratory Medicine, Ludwig-Maximilians-University of Munich, Campus Großhadern, 81377 Munich, Germany.
authors.forename: Petra
authors.initials: P
authors.lastname: Stieber
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D014408:Biomarkers, Tumor / Q000097:blood; D001943:Breast Neoplasms / Q000097:blood* / Q000401:mortality* / Q000473:pathology / Q000628:therapy; D002272:Carcinoembryonic Antigen / Q000097:blood; D018572:Disease-Free Survival; D005260:Female; D006801:Humans; D008875:Middle Aged; D018396:Mucin-1 / Q000097:blood*; D011237:Predictive Value of Tests; D011379:Prognosis; D018719:Erb-b2 Receptor Tyrosine Kinases / Q000032:analysis / Q000097:blood*; D012189:Retrospective Studies
chemical_list: D014408:Biomarkers, Tumor; D002272:Carcinoembryonic Antigen; D018396:Mucin-1; D018719:Erb-b2 Receptor Tyrosine Kinases; C508053:ERBB2 protein, human
keywords: Breast cancer; CA 15-3; HER2 ECD; Shed antigen