title: Serum HER-2 extracellular domain: relationship with clinicobiological presentation and prognostic value before and after primary treatment in 701 breast cancer patients.
abstract: OBJECTIVE
  To determine the clinical correlations and prognostic value of serum HER-2 (sHER-2) before and after primary breast cancer treatment.
  
  
  METHODS
  sHER-2 from 701 consecutive patients with stage I-III tumors (median follow-up 7.7 years) was assayed by an enzyme-linked immunosorbent assay (Immuno 1, Bayer Diagnostics).
  
  
  RESULTS
  The median pretreatment sHER-2 concentration was 8.30 ng/mL (range 3.15-82.00 ng/mL). Forty-seven patients (6.7%) had sHER-2 concentrations >12 ng/mL (cutoff level). Pretreatment sHER-2 correlated positively with CA 15.3 (p=0.0169), pathological tumor size (p=0.0082), number of invaded lymph nodes (pN, p=0.0160) and histological grading (p=0.0086). Kaplan-Meier analyses indicated that pretreatment sHER-2 was of prognostic value for contralateral breast cancer (p=0.0018), metastasis-free survival (MFS) (p=0.0008) - particularly lung (p=0.0082) and liver metastases (p=0.0035) - and overall disease-specific survival (DSS) (p=0.0020). According to pN status, pretreatment sHER-2 was of prognostic value only for pN-positive patients (p=0.0017). When combined with estradiol or progesterone receptor status, patients with elevated sHER-2 and receptor-negative tumors had a significantly shorter DSS (p<0.0001 for both receptors). Post-treatment sHER-2 also had individual prognostic value for MFS (p=0.0144) and DSS (p=0.0212). In multivariate analysis, only sHER-2 after primary treatment was an independent prognostic variable for MFS and DSS (p=0.0078 and p=0.0058, respectively).
  
  
  CONCLUSIONS
  sHER-2 elevation in early breast cancer correlates with the principal criteria of tumor aggressiveness, thus permitting selection of patients with a high risk of visceral metastases and contralateral breast tumors. Post-treatment sHER-2 is an independent prognostic factor enabling to identify patients likely to benefit from aggressive adjuvant treatments.
authors.affiliation: Service d'Oncologie Médicale, Hôpital Européen Georges Pompidou, Paris, France.
authors.forename: M
authors.initials: M
authors.lastname: Saghatchian
authors.forename: S
authors.initials: S
authors.lastname: Guepratte
authors.forename: K
authors.initials: K
authors.lastname: Hacene
authors.forename: R
authors.initials: R
authors.lastname: Neumann
authors.forename: J L
authors.initials: JL
authors.lastname: Floiras
authors.forename: M F
authors.initials: MF
authors.lastname: Pichon
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D014408:Biomarkers, Tumor / Q000097:blood*; D001943:Breast Neoplasms / Q000097:blood* / Q000473:pathology; D018572:Disease-Free Survival; D004797:Enzyme-Linked Immunosorbent Assay; D005260:Female; D006801:Humans; D008168:Lung / Q000473:pathology; D008198:Lymph Nodes / Q000473:pathology; D008207:Lymphatic Metastasis; D008875:Middle Aged; D018396:Mucin-1 / Q000096:biosynthesis; D009362:Neoplasm Metastasis; D011379:Prognosis; D017434:Protein Structure, Tertiary; D018719:Erb-b2 Receptor Tyrosine Kinases / Q000097:blood* / Q000737:chemistry*; D012008:Recurrence; D013997:Time Factors
chemical_list: D014408:Biomarkers, Tumor; D018396:Mucin-1; D018719:Erb-b2 Receptor Tyrosine Kinases