Abstract B072: Reproducibility of plasma metabolome over 1 year in a population-based study of Black breast cancer survivors
Authors: Qin Bo , Vyas Madhir , Moore Steven C. , Su Xiaoyang , White Eileen , Ambrosone Christine B. , Demissie Kitaw , Hong Chi-Chen , Bandera Elisa V. 
Published: December 2023

Abstract
Background: African American/Black women have higher rates of breast cancer (BrCa) mortality and morbidity than White women. The metabolomics approach using blood samples from epidemiological studies has the potential to elucidate pathways or uncover biomarkers for adverse BrCa outcomes. Therefore, understanding the within-person reproducibility of the blood metabolome of BrCa survivors and factors that influence metabolite levels over time is crucial. However, the stability of blood metabolome among Black BrCa survivors is unknown. Objective: This study aimed to estimate the within-person reproducibility of metabolites over 1 year via global untargeted metabolomic profiling of plasma samples collected in the Women’s Circle of Health Follow-Up Study (WCHFS), a population-based longitudinal study of Black BrCa survivors in New Jersey. The study also aims to identify factors associated with reproducibility. Methods: We estimated the metabolite reproducibility among 61 Black women with BrCa diagnosed between 2012 and 2017 in WCHFS. Plasma samples were collected once for each participant at ~2 and 3 years post-diagnosis, respectively, and analyzed at Metabolon via ultrahigh performance liquid chromatography-tandem mass spectrometry. Using a mixed-effects model, we calculated the intraclass correlation coefficients (ICC) for each metabolite by dividing the between-person variance by the total variance (i.e., within- and between-person variances). ICCs were compared by age, obesity status, estrogen receptor (ER) status, and seasons, fasting status and time interval between two visits when blood samples were collected. Statistical significance was determined using the Wilcoxon test. Results: Of the 857 named metabolites identified after excluding those undetectable in ≥80% of samples or with a coefficient of variance≥0.25, the median ICC was 0.58 (interquartile range [IQR]: 0.44-0.70). 16.6% had high within-person reproducibility (ICC≥0.75), spanning across all metabolite classes, while 65.6% had an ICC within 0.4-0.75, and the remaining 17.9% had an ICC&lt;0.4. Significant differences in ICCs were noted by participants’ age (median ICC [IQR; same below]: 0.56 [0.40 - 0.68] for younger women, i.e. ≤ 55.6 years vs. 0.61 [0.44 - 0.73] for older women), obesity status (0.55 [0.40 - 0.68] for non-obese vs. 0.62 [0.46 - 0.75] for obese), and ER status (0.56 [0.41 - 0.68] for ER+ vs. 0.62 [0.45 - 0.79] for ER-). The reproducibility also differed by fasting status (0.63 [0.45 - 0.77] for fasting vs. 0.53 [0.39 - 0.67] for non-fasting), but not the seasons or time interval between blood collections. Conclusion: The within-person reproducibility of plasma metabolites over 1 year among Black breast cancer survivors was generally reasonable, suggesting a single-time-point measurement could be useful in evaluating associations between metabolites and BrCa outcomes. However, the reproducibility varied across metabolites and was influenced by participant characteristics and certain sample collection conditions, which need consideration in future analysis or design.
Citation Format: Bo Qin, Madhir Vyas, Steven C. Moore, Xiaoyang Su, Eileen White, Christine B. Ambrosone, Kitaw Demissie, Chi-Chen Hong, Elisa V. Bandera. Reproducibility of plasma metabolome over 1 year in a population-based study of Black breast cancer survivors [abstract]. In: Proceedings of the 16th AACR Conference on the Science of Cancer Health Disparities in Racial/Ethnic Minorities and the Medically Underserved; 2023 Sep 29-Oct 2;Orlando, FL. Philadelphia (PA): AACR; Cancer Epidemiol Biomarkers Prev 2023;32(12 Suppl):Abstract nr B072.