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Breast Cancer Metabolomics

Principal Investigator
Name
Steven Moore
Degrees
Ph.D., M.P.H
Institution
National Cancer Institute
Position Title
Senior Investigator
Email
About this CDAS Project
Study
PLCO (Learn more about this study)
Project ID
PLCO-1981
Initial CDAS Request Approval
Sep 9, 2025
Title
Breast Cancer Metabolomics
Summary
Breast cancer incidence rates have not declined despite improvement in risk prediction and the identification of modifiable risk factors, suggesting the need to identify novel risk factors and etiological pathways involved in this cancer. Metabolomics has emerged as a promising tool to find circulating metabolites associated with breast cancer risk. To date, there have been 11 studies from eight prospective cohorts that have applied metabolomics to prediagnostic blood samples from breast cancer cases and controls. These studies varied in the metabolomics platform used, the number of case and controls, and in the criteria used to define statistically significant associations. While each study identified one or more associated metabolites, replication of the findings is needed to verify the associations with breast cancer risk. Thus far, the associations of several androgen metabolites, lipids, and two amino acids with breast cancer risk have been replicated by two or more of the previous studies.

Not surprisingly, the previous studies with larger study populations identified more metabolites significantly associated with breast cancer risk. The largest single previous study included 1695 cases and a subcohort of 1983 women while, collectively, the previous studies included 7373 cases and 7661 non-cases. Over 86% of these study participants were from COMETS-member cohorts. A meta-analysis of the previous studies will likely identify additional metabolites and may strengthen the evidence for association of previously identified metabolites with breast cancer risk.
Aims

Since previous studies with larger study populations identified more metabolites significantly associated with breast cancer risk. Our overall goal is to conduct a meta-analysis of previous studies including PLCO, CPS-II, CPS-3, NHS, NHS2, and EPIC; to identify additional metabolites and potentially strengthen the evidence for association of previously identified metabolites with breast cancer risk. Our specific aims are:

Aim 1: To identify metabolites associated with breast cancer using a meta-analysis approach using metabolite data from the following cohorts PLCO, CPS-II, CPS-3, NHS, NHS2, and EPIC.

Aim 2: To determine if the metabolite associations with breast cancer risk differ by menopausal status.

Collaborators

Steven Moore National Cancer Institute
Karen Corleto National Cancer Institute
Karen Corleto National Cancer Institute
Eleanor Watts National Cancer Institute