Abstract

BackgroundMetabolomics is emerging as an important tool for detecting differences between diseased and non-diseased individuals. However, prospective studies are limited.MethodsWe examined the detectability, reliability, and distribution of metabolites measured in pre-diagnostic plasma samples in a pilot study of women enrolled in the Northern California site of the Breast Cancer Family Registry. The study included 45 cases diagnosed with breast cancer at least one year after the blood draw, and 45 controls. Controls were matched on age (within 5 years), family status, BRCA status, and menopausal status. Duplicate samples were included for reliability assessment. We used a liquid chromatography/gas chromatography mass spectrometer platform to measure metabolites. We calculated intraclass correlations (ICCs) among duplicate samples, and coefficients of variation (CVs) across metabolites.ResultsOf the 661 named metabolites detected, 338 (51%) were found in all samples, and 490 (74%) in more than 80% of samples. The median ICC between duplicates was 0.96 (25th – 75th percentile: 0.82–0.99). We observed a greater than 20% case-control difference in 24 metabolites (p < 0.05), although these associations were not significant after adjusting for multiple comparisons.ConclusionsThese data show that assays are reproducible for many metabolites, there is a minimal laboratory variation for the same sample, and a large between-person variation. Despite small sample size, differences between cases and controls in some metabolites suggest that a well-powered large-scale study is likely to detect biological meaningful differences to provide a better understanding of breast cancer etiology.

Highlights

  • Metabolomics is emerging as an important tool for detecting differences between diseased and non-diseased individuals

  • We conducted a pilot study to generate preliminary data to assess whether circulating metabolomic profiles could be detected in pre-diagnostic plasma samples of women enrolled in the Breast Cancer Family Registry (BCFR) cohort, and to evaluate the reproducibility of metabolomic assays

  • Among the metabolites that showed a greater than 20% case-control difference, we examined differences among hypothesized predictors of breast cancer risk, including differences by age at blood draw, the number of affected first-degree relatives (Table 3), estrogen receptor (ER) status, and progesterone receptor (PR) status (Table 4)

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Summary

Introduction

Metabolomics is emerging as an important tool for detecting differences between diseased and non-diseased individuals. Most metabolomics studies of breast cancer to date have been conducted in tumor tissues or cell lines and with the goals of distinguishing cancer from normal tissue and cancers with metastasis from those without, as well as identifying therapeutic targets [9,10,11]. Data from these studies have suggested that metabolomic profiles may differ by pathological and molecular subtype of breast cancer. We conducted a pilot study to generate preliminary data to assess whether circulating metabolomic profiles could be detected in pre-diagnostic plasma samples of women enrolled in the Breast Cancer Family Registry (BCFR) cohort, and to evaluate the reproducibility of metabolomic assays

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