Abstract:
:Estrogen receptor (ER)-positive/progesterone receptor (PR)-positive invasive ductal carcinoma accounts for ~45 % of invasive breast cancer (BC) diagnoses in the U.S. Despite reductions in BC mortality attributable to mammography screening and adjuvant hormonal therapy, an important challenge remains the development of clinically useful blood-based biomarkers for risk assessment and early detection. The objective of this study was to identify novel protein markers for ER+/PR+ ductal BC. A nested case-control study was conducted within the Women's Health Initiative observational study. Pre-clinical plasma specimens, collected up to 12.5 months before diagnosis from 121 cases and 121 matched controls, were equally divided into training and testing sets and interrogated using a customized antibody array targeting >2000 proteins. Statistically significant differences (P < 0.05) in matched case versus control signals were observed for 39 candidates in both training and testing sets, and four markers (CSF2, RYBP, TFRC, ITGB4) remained significant after Bonferroni correction (P < 2.03 × 10(-5)). A multivariate modeling procedure based on elastic net regression with Monte Carlo cross-validation achieved an estimated AUC of 0.75 (SD 0.06). Most candidates did not overlap with those described previously for triple-negative BC, suggesting sub-type specificity. Gene set enrichment analyses identified two GO gene sets as upregulated in cases-microtubule cytoskeleton and response to hormone stimulus (P < 0.05, q < 0.25). This study has identified a pool of novel candidate plasma protein biomarkers for ER+/PR+ ductal BC using pre-diagnostic biospecimens. Further validation studies are needed to confirm these candidates and assess their potential clinical utility for BC risk assessment/early detection.
journal_name
Breast Cancer Res Treatjournal_title
Breast cancer research and treatmentauthors
Buas MF,Rho JH,Chai X,Zhang Y,Lampe PD,Li CIdoi
10.1007/s10549-015-3554-5subject
Has Abstractpub_date
2015-09-01 00:00:00pages
445-54issue
2eissn
0167-6806issn
1573-7217journal_volume
153pub_type
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journal_title:Breast cancer research and treatment
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journal_title:Breast cancer research and treatment
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journal_title:Breast cancer research and treatment
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journal_title:Breast cancer research and treatment
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journal_title:Breast cancer research and treatment
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journal_title:Breast cancer research and treatment
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pub_type: 社论
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journal_title:Breast cancer research and treatment
pub_type: 杂志文章,评审
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更新日期:1994-01-01 00:00:00
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journal_title:Breast cancer research and treatment
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journal_title:Breast cancer research and treatment
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journal_title:Breast cancer research and treatment
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journal_title:Breast cancer research and treatment
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