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Detection of elevated plasma levels of epidermal growth factor receptor before breast cancer diagnosis among hormone therapy users.

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.

SUBMITTER: Pitteri SJ

PROVIDER: S-EPMC2970770 | biostudies-literature | 2010 Nov

REPOSITORIES: biostudies-literature

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Detection of elevated plasma levels of epidermal growth factor receptor before breast cancer diagnosis among hormone therapy users.

Pitteri Sharon J SJ Amon Lynn M LM Busald Buson Tina T Zhang Yuzheng Y Johnson Melissa M MM Chin Alice A Kennedy Jacob J Wong Chee-Hong CH Zhang Qing Q Wang Hong H Lampe Paul D PD Prentice Ross L RL McIntosh Martin W MW Hanash Samir M SM Li Christopher I CI

Cancer research 20101019 21

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 t ...[more]

PMID: 20959476

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Project description:INTRODUCTION:Mammographic density (MD) is one of the strongest known breast cancer risk factors. Estrogen and progestin therapy (EPT) has been associated with increases in MD. Dense breast tissue is characterized by increased stromal tissue and (to a lesser degree) increased numbers of breast epithelial cells. It is possible that genetic factors modify the association between EPT and MD, and that certain genetic variants are particularly important in determining MD in hormone users. We evaluated the association between MD and 340 tagging single nucleotide polymorphisms (SNPs) from about 30 candidate genes in hormone metabolism/growth factor pathways among women who participated in the Norwegian Breast Cancer Screening Program (NBCSP) in 2004. METHODS:We assessed MD on 2,036 postmenopausal women aged 50 to 69 years using a computer-assisted method (Madena, University of Southern California) in a cross-sectional study. We used linear regression to determine the association between each SNP and MD, adjusting for potential confounders. The postmenopausal women were stratified into HT users (EPT and estrogen-only) and non-users (never HT). RESULTS:For current EPT users, there was an association between a variant in the prolactin gene (PRL; rs10946545) and MD (dominant model, Bonferroni-adjusted P (Pb) = 0.0144). This association remained statistically significant among current users of norethisterone acetate (NETA)-based EPT, a regimen common in Nordic countries. Among current estrogen-only users (ET), there was an association between rs4670813 in the cytochrome P450 gene (CYP1B1) and MD (dominant model, Pb = 0.0396). In never HT users, rs769177 in the tumor necrosis factor (TNF) gene and rs1968752 in the region of the sulfotransferase gene (SULT1A1/SULT1A2), were significantly associated with MD (Pb = 0.0202; Pb = 0.0349). CONCLUSIONS:We found some evidence that variants in the PRL gene were associated with MD in current EPT and NETA users. In never HT users, variants in the TNF and SULT1A1/SULT1A2 genes were significantly associated with MD. These findings may suggest that several genes in the hormone metabolism and growth factor pathways are implicated in determining MD.

Dataset Information

Detection of elevated plasma levels of epidermal growth factor receptor before breast cancer diagnosis among hormone therapy users.

Publications

Detection of elevated plasma levels of epidermal growth factor receptor before breast cancer diagnosis among hormone therapy users.

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