Discovery of Plasma Lipids as Potential Biomarkers Distinguishing Breast Cancer Patients from Healthy Controls

The development of a sensitive and specific blood test for the early detection of breast cancer is crucial to improve screening and patient outcomes. Existing methods, such as mammography, have limitations, necessitating the exploration of alternative approaches, including circulating factors. Using 598 prospectively collected blood samples, a multivariate plasma-derived lipid biomarker signature was developed that can distinguish healthy control individuals from those with breast cancer. Liquid chromatography with high-resolution and tandem mass spectrometry (LC-MS/MS) was employed to identify lipids for both extracellular vesicle-derived and plasma-derived signatures. For each dataset, we identified a signature of 20 lipids using a robust, statistically rigorous feature selection algorithm based on random forest feature importance applied to cross-validated training samples. Using an ensemble of machine learning models, the plasma 20-lipid signature generated an area under the curve (AUC) of 0.95, sensitivity of 0.91, and specificity of 0.79. The results from this study indicate that lipids extracted from plasma can be used as target analytes in the development of assays to detect the presence of early-stage breast cancer.