title: Construction and analysis of the NCI-EDRN breast cancer reference set for circulating markers of disease.
abstract: BACKGROUND
  Many circulating biomarkers have been reported for the diagnosis of breast cancer, but few, if any, have undergone rigorous credentialing using prospective cohorts and blinded evaluation.
  
  
  METHODS
  The NCI Early Detection Research Network (EDRN) has created a prospective, multicenter collection of plasma and serum samples from 832 subjects designed to evaluate circulating biomarkers for the detection and diagnosis of breast cancer. These samples are available to investigators who wish to evaluate their biomarkers using a set of blinded samples. The breast cancer reference set is composed of blood samples collected using a standard operating procedure at four U.S. medical centers from 2008 to 2010 from women undergoing either tissue diagnosis for breast cancer or routine screening mammography. The reference set contains samples from women with incident invasive cancer (n = 190), carcinoma in situ (n = 55), benign pathology with atypia (n = 63), benign disease with no atypia (n = 231), and women with no evidence of breast disease by screening mammography (BI-RADS 1 or 2, n = 276). Using a subset of plasma samples (n = 505) from the reference set, we analyzed 90 proteins by multiplexed immunoassays for their potential utility as diagnostic markers.
  
  
  RESULTS
  We found that none of these markers is useful for distinguishing cancer from benign controls. However, elevated CA-125 does appear to be a candidate marker for estrogen receptor-negative cancers.
  
  
  CONCLUSIONS
  Markers that can distinguish benign breast conditions from invasive cancer have not yet been found.
  
  
  CONCLUSIONS
  Availability of prospectively collected samples should improve future validation efforts.
authors.affiliation: Department of Surgery, Duke University, Durham, North Carolina. marks003@mc.duke.edu.
authors.forename: Jeffrey R
authors.initials: JR
authors.lastname: Marks
authors.affiliation: Center for Personalized Diagnostics, Biodesign Institute, Arizona State University, Tempe, Arizona.
authors.forename: Karen S
authors.initials: KS
authors.lastname: Anderson
authors.affiliation: Medical Oncology, Fox Chase Cancer Center, Philadelphia, Pennsylvania.
authors.forename: Paul
authors.initials: P
authors.lastname: Engstrom
authors.affiliation: Department of Pathology and Laboratory Medicine, University of Kansas Medical Center, Kansas City, Kansas.
authors.forename: Andrew K
authors.initials: AK
authors.lastname: Godwin
authors.affiliation: Department of Surgery, University of California, San Francisco, San Francisco, California.
authors.forename: Laura J
authors.initials: LJ
authors.lastname: Esserman
authors.affiliation: Fred Hutchinson Cancer Research Center, Seattle, Washington.
authors.forename: Gary
authors.initials: G
authors.lastname: Longton
authors.affiliation: Department of Statistical Science, Duke University, Durham, North Carolina.
authors.forename: Edwin S
authors.initials: ES
authors.lastname: Iversen
authors.affiliation: Meso Scale Diagnostics, LLC., Rockville, Maryland.
authors.forename: Anu
authors.initials: A
authors.lastname: Mathew
authors.affiliation: National Cancer Institute, NIH, Bethesda, Maryland.
authors.forename: Christos
authors.initials: C
authors.lastname: Patriotis
authors.affiliation: Fred Hutchinson Cancer Research Center, Seattle, Washington.
authors.forename: Margaret S
authors.initials: MS
authors.lastname: Pepe
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D014408:Biomarkers, Tumor / Q000097:blood*; D001943:Breast Neoplasms / Q000097:blood* / Q000473:pathology; D055088:Early Detection of Cancer; D005260:Female; D006801:Humans; D007118:Immunoassay / Q000379:methods; D008875:Middle Aged; D009363:Neoplasm Proteins / Q000097:blood*; D011446:Prospective Studies; D012016:Reference Values; D055815:Young Adult
chemical_list: D014408:Biomarkers, Tumor; D009363:Neoplasm Proteins