CyTOF profiling and modelling showed KRT14 modulation impacted protein expression signatures associated with ageing and risk.<h4>Interpretation</h4>Mechano-RISQ offers a proof of principle approach for identifying individuals at elevated risk of breast cancer, especially among average-risk populations, and may complement existing risk models by incorporating biophysical measures of mammary epithelial cell ageing.<h4>Funding</h4>NIH R01EB024989, R01CA237602, and P30CA033572, DOD BC181737, American Cancer Society-Fred Ross Desert Spirit Postdoctoral Fellowship (PF-21-184-01-CSM). The gene discussed is KRT14; the disease is breast cancer.