Detection of Elevated Plasma Levels of Epidermal Growth Factor Receptor Before Breast Cancer Diagnosis among Hormone Therapy Users
Year: 2010
Type: article
Study design: Observational Study
Abstract: Applying advanced proteomic technologies to prospectively collected specimens from large studies is one means of identifying preclinical changes in plasma proteins that are potentially relevant to the early detection of diseases such as breast cancer. We conducted 14 independent quantitative proteomics experiments comparing pooled plasma samples collected from 420 estrogen receptor-positive (ER(+)) breast cancer patients ≤17 months before their diagnosis and matched controls. Based on the more than 3.4 million tandem mass spectra collected in the discovery set, 503 proteins were quantified, of which 57 differentiated cases from controls with a P value of <0.1. Seven of these proteins, for which quantitative ELISA assays were available, were assessed in an independent validation set. Of these candidates, epidermal growth factor receptor (EGFR) was validated as a predictor of breast cancer risk in an independent set of preclinical plasma samples for women overall [odds ratio (OR), 1.44; P = 0.0008] and particularly for current users of estrogen plus progestin (E + P) menopausal hormone therapy (OR, 2.49; P = 0.0001). Among current E + P users, the EGFR sensitivity for breast cancer risk was 31% with 90% specificity. Whereas the sensitivity and specificity of EGFR are insufficient for a clinically useful early detection biomarker, this study suggests that proteins that are elevated preclinically in women who go on to develop breast cancer can be discovered and validated using current proteomic technologies. Further studies are warranted to examine the role of EGFR and to discover and validate other proteins that could potentially be used for early detection of breast cancer.
Source: Cancer Research
Institution: Fred Hutch Cancer Center
Language: English
Subfield: Spectroscopy
Field: Chemistry
Domain: Physical Sciences
Open Access status: bronze
Funders: U.S. Department of Health and Human Services, Brigham and Women's Hospital, Kaiser Permanente, Brown University, University of Miami, Wayne State University, Ohio State University, Emory University, Northwestern University, George Washington University, Wake Forest University, University of Minnesota, University of Pittsburgh, University of Cincinnati, University of Nevada, Reno, National Institutes of Health, Health Science Center, University of Tennessee, University of North Carolina at Chapel Hill, University at Buffalo, National Heart, Lung, and Blood Institute, National Cancer Institute
Awards: G109231058, G1107292973, G1526714683, G156924709, G1593340546, G1617453120, G1646017446, G206718646, G2253702613, G2286437695, G2295046671, G2417273319, G2547046739, G257474614, G2852769941, G3544793024, G3642616392, G413560588, G4214622172, G4216744017, G4281851297, G429396632, G4321061599, G445374210, G4454202622, G4560602636, G484043965, G4940723635, G5183277930, G530368906, G532295152, G555506801, G603760282, G6464247198, G7066869570, G7071300326, G7223985928, G7272550893, G7323080267, G7582705761, G8780700017, G8934942062, G9000002220, G9000015938, G9000016408, G9000029166, G9000072420, G9000099044, G9000151586, G9000284018, G999174792
OpenAlex ID: W2041675960