title: High and differential expression of HER-2/neu extracellular domain in bilateral ductal fluids from women with unilateral invasive breast cancer.
abstract: OBJECTIVE
  Overexpression of HER-2/neu is associated with aggressive diseaseand perhaps with increased risk of breast cancer when presentin benign breast tissue. Breast ductal fluid can be obtained from women by simple nipple aspiration and may be useful for analyzing the microenvironment of the breast.
  
  
  METHODS
  After obtaining informed consent, we prospectively compared the volume of fluid collected, protein concentration, and level of HER-2/neu expression in nipple aspiration fluid (NAF) samples from both breasts and serum samples in 65 patients with unilateral primary invasive breast cancer (median age, 54 years). HER-2/neu concentrations were determined by immunoassay, with a sensitivity of 0.1 ng/ml.
  
  
  RESULTS
  The mean NAF volume obtained and the mean NAF protein concentration were no different in the normal versus the affected breast (62.4 versus 60.4 micro l and 140.9 versus 107.8 mg/ml, respectively). Mean serum HER-2/neu level was 4.36 ng/ml (range, 0-16.8 ng/ml), approximately 50 times less than the mean NAF HER-2/neu level from all patients and all breasts (209.2 ng/ml; range, 1.0-3480.0). NAF HER-2/neu levels were significantly correlated between breasts for each individual patient (r = 0.302; P = 0.038). HER-2/neu-overexpressing tumors produced significantly more HER-2/neu in the affected breast (653.6 ng/ml) than in the unaffected breast (101.7 ng/ml) or serum (3.46 ng/ml; P = 0.016).
  
  
  CONCLUSIONS
  Nipple aspiration is a noninvasive method for detecting tumor-specific relevant molecular changes from ductal fluid. The presence of high HER-2/neu levels in the ductal systems of breast cancer patients may have clinical implications for monoclonal antibody directed therapy.
authors.affiliation: Department of Surgical Oncology, The University of Texas M. D. Anderson Cancer Center, Houston, Texas 77030, USA.
authors.forename: Henry M
authors.initials: HM
authors.lastname: Kuerer
authors.forename: Patricia A
authors.initials: PA
authors.lastname: Thompson
authors.forename: Savitri
authors.initials: S
authors.lastname: Krishnamurthy
authors.forename: Herbert A
authors.initials: HA
authors.lastname: Fritsche
authors.forename: Sylvie M
authors.initials: SM
authors.lastname: Marcy
authors.forename: Gildy V
authors.initials: GV
authors.lastname: Babiera
authors.forename: S Eva
authors.initials: SE
authors.lastname: Singletary
authors.forename: Massimo
authors.initials: M
authors.lastname: Cristofanilli
authors.forename: Nour
authors.initials: N
authors.lastname: Sneige
authors.forename: Kelly K
authors.initials: KK
authors.lastname: Hunt
mesh_terms: D000328:Adult; D000368:Aged; D014408:Biomarkers, Tumor / Q000097:blood; D012634:Bodily Secretions / Q000378:metabolism*; D001940:Breast / Q000378:metabolism; D001943:Breast Neoplasms / Q000097:blood / Q000378:metabolism* / Q000473:pathology*; D002277:Carcinoma / Q000097:blood / Q000145:classification / Q000378:metabolism / Q000473:pathology; D005260:Female; D006801:Humans; D008875:Middle Aged; D009361:Neoplasm Invasiveness; D009367:Neoplasm Staging; D009558:Nipples / Q000473:pathology; D044469:Racial Groups; D018719:Erb-b2 Receptor Tyrosine Kinases / Q000097:blood / Q000378:metabolism*; D012016:Reference Values; D013781:Texas
chemical_list: D014408:Biomarkers, Tumor; D018719:Erb-b2 Receptor Tyrosine Kinases