TY - JOUR
T1 - High and differential expression of HER-2/neu extracellular domain in bilateral ductal fluids from women with unilateral invasive breast cancer
AU - Kuerer, Henry M.
AU - Thompson, Patricia A.
AU - Krishnamurthy, Savitri
AU - Fritsche, Herbert A.
AU - Marcy, Sylvie M.
AU - Babiera, Gildy V.
AU - Singletary, S. Eva
AU - Cristofanilli, Massimo
AU - Sneige, Nour
AU - Hunt, Kelly K.
PY - 2003/2/1
Y1 - 2003/2/1
N2 - Purpose: Overexpression of HER-2/neu is associated with aggressive disease and perhaps with increased risk of breast cancer when present in 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. Experimental Design: 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 μ1 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), ∼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/neuoverexpressing 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.
AB - Purpose: Overexpression of HER-2/neu is associated with aggressive disease and perhaps with increased risk of breast cancer when present in 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. Experimental Design: 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 μ1 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), ∼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/neuoverexpressing 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.
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M3 - Article
C2 - 12576424
AN - SCOPUS:0037312435
SN - 1078-0432
VL - 9
SP - 601
EP - 605
JO - Clinical Cancer Research
JF - Clinical Cancer Research
IS - 2
ER -