Metastatic Breast Cancer and Pre-Diagnostic Blood Gene Expression Profiles—The Norwegian Women and Cancer (NOWAC) Post-Genome Cohort

Abstract

Breast cancer patients with metastatic disease have a higher incidence of deaths from breast cancer than patients with early-stage cancers. Recent findings suggest that there are differences in immune cell function between metastatic and non-metastatic cases, even years before diagnosis. We have analyzed whole blood gene expression by Illumina bead chips in blood samples taken using the PAXgene blood collection system up to two years before diagnosis. The final study sample included 197 breast cancer cases and 197 age-matched controls. We defined a causal directed acyclic graph to guide a Bayesian data analysis to estimate the risk of metastasis associated with the expression of all genes and with relevant sets of genes. We ranked genes and gene sets according to the sign probability for excess risk. Among the screening detected cancers, 82% were without metastasis, compared to 53% of between-screening detected cancers. Among the highest ranking genes and gene sets associated with metastasis risk, we identified plasmacytiod dentritic cell function, the SLC22 family of transporters, and glutamine metabolism as potential links between the immune system and metastasis. We conclude that there may be potentially wide-reaching differences in blood gene expression profiles between metastatic and non-metastatic breast cancer cases up to two years before diagnosis, which warrants future study.