title: Relationship of serum HER-2/neu and serum CA 15-3 in patients with metastatic breast cancer.
abstract: BACKGROUND
  Serum HER-2/neu antigen concentrations have been reported to correlate with increased tumor volume in patients with breast cancer. We measured serum CA 15-3, a surrogate marker of disease burden, and correlated serum CA 15-3 with serum HER-2/neu and analyzed the association of both markers with clinical outcomes.
  
  
  METHODS
  Pretreatment serum samples from 566 patients were retrospectively analyzed from 2 phase III clinical trials of estrogen receptor-positive (ER(+)), ER(-)/progesterone receptor-positive, or ER status unknown metastatic breast cancer patients randomized in two similar studies to receive second-line hormone therapy with either megestrol acetate or an aromatase inhibitor (fadrozole). The extracellular domain of the HER-2/neu (c-erbB-2) oncogene and serum CA 15-3 were measured by ELISA on the Bayer Immuno 1.
  
  
  RESULTS
  Serum HER-2/neu protein was increased in 168 patients (30%), and CA 15-3 was increased in 337 (60%) patients. Serum CA 15-3 and HER-2/neu were weakly correlated (r = 0.39; P <0.0001). The clinical benefit (complete responses plus partial responses plus stable disease) of endocrine therapy was significantly lower in patients with increased serum HER-2/neu. When adjusted for serum HER-2/neu, serum CA 15-3 was not predictive of response rates. The median time to progression was shorter in patients with increased serum HER-2/neu (89 days) compared with patients with normal serum HER-2/neu (176 days). Survival was significantly shorter in patients with increased serum HER-2/neu (513 vs 869 days; P <0.0001) or increased serum CA 15-3 (689 vs 939 days; P <0.0001). This observation was confirmed by multivariate analysis.
  
  
  CONCLUSIONS
  Serum HER-2/neu is a significant independent predictive and prognostic factor in hormone receptor-positive metastatic breast cancer, even when adjusted for tumor burden as measured by CA 15-3. The combination of increased serum HER-2/neu and increased serum CA 15-3 predicts a worse prognosis than does increased CA 15-3 alone.
authors.affiliation: The M.S. Hershey Medical Center, PA 17033, USA.
authors.forename: Suhail M
authors.initials: SM
authors.lastname: Ali
authors.forename: Kim
authors.initials: K
authors.lastname: Leitzel
authors.forename: Vernon M
authors.initials: VM
authors.lastname: Chinchilli
authors.forename: Linda
authors.initials: L
authors.lastname: Engle
authors.forename: Laurence
authors.initials: L
authors.lastname: Demers
authors.forename: Harold A
authors.initials: HA
authors.lastname: Harvey
authors.forename: Walter
authors.initials: W
authors.lastname: Carney
authors.forename: Jeffrey W
authors.initials: JW
authors.lastname: Allard
authors.forename: Allan
authors.initials: A
authors.lastname: Lipton
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D018931:Antineoplastic Agents, Hormonal; D001943:Breast Neoplasms / Q000097:blood* / Q000188:drug therapy / Q000473:pathology; D004311:Double-Blind Method; D017316:Fadrozole / Q000627:therapeutic use; D005260:Female; D006801:Humans; D019290:Megestrol Acetate / Q000627:therapeutic use; D008875:Middle Aged; D018396:Mucin-1 / Q000097:blood*; D009362:Neoplasm Metastasis; D011379:Prognosis; D018719:Erb-b2 Receptor Tyrosine Kinases / Q000097:blood*; D012189:Retrospective Studies
chemical_list: D018931:Antineoplastic Agents, Hormonal; D017316:Fadrozole; D019290:Megestrol Acetate; D018396:Mucin-1; D018719:Erb-b2 Receptor Tyrosine Kinases