Construction and analysis of the NCI-EDRN breast cancer reference set for circulating markers of disease.
Abstract
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.
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.
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.
Markers that can distinguish benign breast conditions from invasive cancer have not yet been found.
Availability of prospectively collected samples should improve future validation efforts.
Biomarkers
The following biomarkers make reference to this publication:
- ADIPOQ
- AFP
- AKR1B1
- AKR1C2
- ALPL
- ANXA1
- BCL2L2
- BGLAP
- CA125
- CA15-3
- CA19-9
- CCL11
- CCL13
- CCL17
- CCL2
- CCL22
- CCL26
- CCL4
- CCL5
- CDH1
- CDH3
- CEACAM5
- CHGA
- CRP
- CRYAB
- CSF1
- CXCL10
- CXCL8
- EGFR
- ERBB2
- FABP5
- FGF2
- FLT1
- FLT3LG
- GCLM
- GLO1
- GPI
- GSTM1
- GSTM2
- HGF
- ICAM1
- IFNG
- IL10
- IL12
- IL13
- IL18
- IL1B
- IL2
- IL4
- IL5
- KDR
- LBP
- MAGEA4
- MAPK14
- MBD1
- MET
- MMP1
- MMP10
- MMP2
- MMP3
- MMP9
- MSLN
- NECTIN4
- NME2
- ODC1
- Osteopontin
- PIGF
- PRDX4
- PRL
- PSA
- PSAT1
- PTPA
- RAC1
- S100A4
- S100A6
- SAA@
- SAT1
- SATL1
- SERPINB3
- SFN
- SOST
- TEK
- TIMP1
- TNF
- TNFRSF11B
- TNFRSF1A
- TNFRSF1B
- VCAM1
- VEGFC
- VEGFD
Protocols
The following 2 protocols are associated with this publication:
EDRN PI Authors
Medline Author List
- Anderson KS
- Engstrom P
- Esserman LJ
- Godwin AK
- Iversen ES
- Longton G
- Marks JR
- Mathew A
- Patriotis C
- Pepe MS