Preventing TNBC in Obese Women

Project Summary

Triple-Negative Breast Cancer (TNBC) is aggressive and disproportionately affects obese premenopausal women. This project evaluates GLP-1 receptor agonists (tirzepatide) as a preventive strategy in high-risk women, integrating multi-omics biomarker discovery. Participants recruited from obesity clinics undergo longitudinal monitoring with biospecimens collected at multiple time points. Proteomics, metabolomics, and epigenetic analyses are applied to identify biomarkers predictive of TNBC risk and intervention response. Expected outcomes include:

· Novel biomarkers linking obesity-driven biology to TNBC.

· Evidence for pharmacologic prevention using GLP-1 receptor agonists.

· Translational findings to guide precision prevention policies in Saudi Arabia.

Expected impact includes the development of biomarker-guided preventive strategies that can be applied clinically and incorporated into cancer screening policies.

Collaborators

Oncology, Obesity & Nutrition Clinics, molecular oncology, cell therapy & immunology, center for genomic medicine at KFSHRC; international collaborators in cancer epidemiology.

Figure

Figure. Integrated summary of subtype epidemiology and putative obesity–TNBC mechanisms Panel A: Distribution of molecular subtypes in premenopausal cases. Panel B: Adjusted ORs (95% CIs) for key risk factors by subtype. Panel C: Conceptual schematic linking obesity-related inflammation (e.g., IL-6/TNF-α/CRP) to JAK/STAT and NF-κB pathway activation, immune evasion, and ER-loss consistent with TNBC development; schematic is hypothesis-generating and not drawn to scale.

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