No abstract

Purpose: Breast cancer is a major cause of death in occidental women. Mechanisms involved in its etiology remain misunderstood. Metabolomics is a powerful tool which may help elucidating novel biological pathways and identify new biomarkers in order to predict breast cancer well before symptoms appear. The aim of this study was to investigate whether untargeted metabolomic signatures from blood draws of healthy women could contribute to better understand and predict the long-term risk of developing breast cancer. Methods: A nested case-control study was conducted within the SU.VI.MAX prospective cohort (13 years of follow-up) to analyze baseline plasma samples of 211 incident breast cancer cases and 211 matched controls by LC-MS mass spectrometry. Multivariable conditional logistic regression models were computed. Results: 83 ions were significantly associated (corrected-pvalue <0.05) with breast cancer risk. Notably, we observed that a lower plasma level of O-succinyl-homoserine and higher plasma levels of valine/norvaline, glutamine/isoglutamine, 5-aminovaleric acid, phenylalanine, tryptophane, γ-glutamyl-threonine, ATBC, 2-amino-cyanobutanoic acid and pregnene-triol sulfate were associated with an increased risk of developing breast cancer during follow-up. Corrected-pvalues ranged from 0.009 (OR=1.43[1.14-1.78] for phenylalanine and OR=1.45[1.15-1.83] for valine/norvaline) to 0.03 (OR=1.28[1.03-1.58] for 2-amino-cyano-butanoic acid). Conclusion: Several pre-diagnostic plasmatic metabolites are strongly associated with long-term breast cancer risk. If confirmed in other independent cohort studies, these results could help to identify healthy women at higher risk of developing breast cancer in the subsequent decade and to propose a better understanding of the complex mechanisms involved in its etiology. Trial registration: SU.VI.MAX, clinicaltrials.gov NCT00272428. Registered 3 January 2006 Keywords: Metabolomics, breast cancer, mass spectrometry, plasma, prospective study Citation Format: Lucie L, Céline D, Bernard L, Aicha D, Adrien R, Marie-Paule V, Mélanie P, Marie L, Tom F, Delphine C, Laurent Z, Pilar G, Serge H, Mélanie D, Valentin P, Bernard S, Paule L-M, Emmanuelle K-G, Nathalie D-P, Claudine M, Stéphanie D, Estelle P-G, Mathilde T. Plasma metabolomic signatures associated with long-term breast cancer risk in the SU.VI.MAX prospective cohort [abstract]. In: Proceedings of the 2018 San Antonio Breast Cancer Symposium; 2018 Dec 4-8; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2019;79(4 Suppl):Abstract nr P4-10-17.