Cancer esearch ention and Epidemiology ection of Elevated Plasma Levels of Epidermal Growth tor Receptor Before Breast Cancer Diagnosis R ng Hormone Therapy Users

nloaded lying advanced proteomic technologies to prospectively collected specimens from large studies is one of identifying preclinical changes in plasma proteins that are potentially relevant to the early detection eases such as breast cancer. We conducted 14 independent quantitative proteomics experiments ring pooled plasma samples collected from 420 estrogen receptor–positive (ER) breast cancer patients onths before their diagnosis and matched controls. Based on the more than 3.4 million tandem mass a collected in the discovery set, 503 proteins were quantified, of which 57 differentiated cases from conith a P value of <0.1. Seven of these proteins, for which quantitative ELISA assays were available, were ed in an independent validation set. Of these candidates, epidermal growth factor receptor (EGFR) was ted as a predictor of breast cancer risk in an independent set of preclinical plasma samples for women l [odds ratio (OR), 1.44; P = 0.0008] and particularly for current users of estrogen plus progestin (E + P) ausal hormone therapy (OR, 2.49; P = 0.0001). Among current E + P users, the EGFR sensitivity for breast risk was 31% with 90% specificity. Whereas the sensitivity and specificity of EGFR are insufficient for a lly useful early detection biomarker, this study suggests that proteins that are elevated preclinically in n who go on to develop breast cancer can be discovered and validated using current proteomic techwome nologies. 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. Cancer Res; 70(21); 8598–606. ©2010 AACR.