A Multiomics, Molecular Atlas of Breast Cancer Survivors

Abstract

Breast cancer imposes a significant burden globally. While the survival rate is steadily improving, much remains to be elucidated. This observational, single time point, multiomic study utilizing genomics, proteomics, targeted and untargeted metabolomics, and metagenomics in a breast cancer survivor (BCS) and age-matched healthy control cohort (N = 100) provides deep molecular phenotyping of breast cancer survivors. In this study, the BCS cohort had significantly higher polygenic risk scores for breast cancer than the control group. Carnitine and hexanoyl carnitine were significantly different. Several bile acid and fatty acid metabolites were significantly dissimilar, most notably the Omega-3 Index (O3I) (significantly lower in BCS). Proteomic and metagenomic analyses identified group and pathway differences, which warrant further investigation. The database built from this study contributes a wealth of data on breast cancer survivorship where there has been a paucity, affording the ability to identify patterns and novel insights that can drive new hypotheses and inform future research. Expansion of this database in the treatment-naïve, newly diagnosed, controlling for treatment confounders, and through the disease progression, can be leveraged to profile and contextualize breast cancer and breast cancer survivorship, potentially leading to the development of new strategies to combat this disease and improve the quality of life for its victims.

Keywords

• breast cancer survivors
• breast cancer
• multiomics
• genomics
• metagenomics
• metabolomics