Reproducibility of Plasma Metabolome Over 1 Year in a Population-based Cohort of Black Breast Cancer Survivors.

Background: The metabolomics approach using blood samples from epidemiological studies has the potential to elucidate pathways or uncover biomarkers for breast cancer (BC) outcomes. Therefore, understanding the within-person reproducibility of the blood metabolome and the factors that influence metabolite levels over time in BC survivors are crucial, but these remain largely unknown.

Methods: We estimated the within-person reproducibility of plasma metabolites in 61 Black BC survivors from the Women's Circle of Health Follow-Up Study. Samples were collected from each participant at two time points, approximately two and three years post-diagnosis. Untargeted metabolomic profiles were analyzed by Metabolon using ultrahigh-performance liquid chromatography-tandem mass spectrometry. We calculated the intraclass correlation coefficients (ICC) for each metabolite by dividing the between-person variance by the total variance. ICCs were compared across preanalytical factors (e.g., fasting) and participant characteristics using the Wilcoxon test.

Results: Among 857 named metabolites, the median ICC was 0.58 (interquartile range [IQR]: 0.44-0.70). 16.6% of the metabolites showed high within-person reproducibility (ICC≥0.75), spanning all metabolite classes, while 65.6% had an ICC within 0.4-0.75, and 17.9% had an ICC<0.4. Reasonable ICCs were also observed for non-fasting samples (median 0.53, IQR: 0.39-0.67), although lower than those for fasting samples (median 0.63, IQR: 0.45-0.77). ICCs were slightly lower in younger, non-obese participants and in women with estrogen receptor-positive BC.

Conclusions: The within-person reproducibility of plasma metabolites over 1 year among BC survivors was generally acceptable.

Impact: A single-time-point measurement could be useful in evaluating associations between metabolites and breast cancer outcomes.