IARC 60th Anniversary - 19-21 May 2026
Session : Breast Cancer Etiology: New Findings on Lifestyle, Environmental, and Biological Factors
A metabolomics approach to uncover the role of lifestyle in breast cancer survival: the MAESTRA project
HIS M. 1,2,3, CASTRO-ESPIN C. 3, MAHAMAT-SALEH Y. 3, NAVIONIS A. 3, NADAL N. 4,5, TRÉDAN O. 6,7, FERVERS B. 1,2, AGUDO A. 4,5, CROUS-BOU M. 4,5, DOSSUS L. 3, RINALDI S. 3, PÉROL O. 1,2
1 Prevention Cancer Environment Department, Centre Leon Bérard, Lyon, France; 2 Inserm U1296, Lyon, France; 3 International Agency for Research on Cancer (IARC/WHO), Nutrition and Metabolism Branch, Lyon, France; 4 Unit of Nutrition and Cancer, Catalan Institute of Oncology-ICO, Barcelona, Spain; 5 Nutrition and Cancer Group, Epidemiology, Public Health, Cancer Prevention and Palliative Care Program, Bellvitge Biomedical Research Institute-IDIBELL, Barcelona, Spain; 6 Department of Medical Oncology, Centre Léon Bérard, Lyon, France; 7 Cancer Research Center of Lyon, UMR Inserm 1052/CNRS 5286, Lyon, France
Background
Breast cancer survival varies according to tumor and patient characteristics. Modifiable lifestyle factors, such as nutrition and physical activity, may also influence prognosis, although the underlying biological mechanisms are not well characterized. Metabolomics has emerged as a powerful tool to characterize metabolic pathways related to breast cancer etiology and lifestyle exposures. However, its application to biospecimens from breast cancer patients to inform tertiary prevention strategies remains limited.
The MAESTRA project aims to address this gap by integrating prospective epidemiological data and randomized trial evidence to identify lifestyle- and nutrition?related metabolites associated with survival.
Objectives
We aim to: 1) identify circulating metabolites associated with breast cancer survival; 2) examine associations between lifestyle and nutritional factors and concentrations of survival?related metabolites; and 3) evaluate whether lifestyle interventions can modify concentrations of these metabolite in breast cancer patients.
Methods
We first leveraged data from the European Prospective Investigation into Cancer and Nutrition (EPIC).
Within EPIC, we selected 1,624 women diagnosed with a first primary invasive breast cancer with available targeted metabolomics data (average follow-up after diagnosis: 7 years, 238 deaths). A panel of 147 metabolites (acylcarnitines, amino acids, biogenic amines, glycerophospholipids, sphingolipids, and hexose) was analyzed in pre-diagnostic blood samples collected on average eight years before diagnosis. Associations between metabolite concentrations and all?cause and breast cancer?specific mortality were evaluated using Cox proportional hazards models adjusted for relevant covariates.
To investigate whether blood concentrations of relevant metabolites are modifiable, we are using a similar targeted metabolomics approach to analyze repeated blood samples from participants in two randomized controlled trials among breast cancer patients: DISCO, a physical activity intervention (France, NCT03529383, n=244 participants with repeated blood samples), and PREDICOP, a combined diet and physical activity intervention (Spain, NCT0203563, n=300 participants with repeated blood samples).
Results
Observational analyses in EPIC are underway, and preliminary findings on associations between pre?diagnosis metabolite concentrations and breast cancer survival will be presented. Integration with lifestyle and nutritional data and analyses from DISCO and PREDICOP will allow further exploration of metabolic signatures that may be modifiable through targeted behavioral interventions.
Conclusions/Implications
This project will provide new insights into metabolic profiles associated with breast cancer survival, and help identify lifestyle and nutrition-related pathways that may be relevant for tertiary prevention in breast cancer patients.