Circulating enolase 1 as a diagnostic biomarker for early-stage breast cancer.

Diagnosis of stage 1 breast cancer is challenging as small tumors are often left undetected by conventional imaging techniques. In addition, ~80% of detected breast masses are classified as benign, which means that a large proportion of diagnostic needle biopsies lead to unnecessary psychological stress and medical costs. We investigated circulating extracellular vesicles (EVs) as potential carriers of unique cancer-associated proteins capable of reporting on a breast cancer diagnosis. We isolated EVs from healthy (19), benign (19), and stage 1 breast cancer patient (86) plasma samples using size exclusion chromatography. Mass spectrometry identified 94 significantly changed proteins in the plasma EVs from breast cancer patients. Analysis of a subset of these proteins using a cohort of pre- and post-operative breast cancer patient plasma EVs identified enolase 1 as a promising biomarker. We further validated enolase 1 in a larger patient cohort by high-throughput ELISA of plasma. Enolase 1 was found to be significantly elevated in plasma from stage 1 breast cancer patients compared to healthy and benign individuals, and decreased in post-operative plasma upon tumor removal. Our findings suggest that an enolase 1 liquid blood biopsy could be used to support the detection of breast cancer at the earliest, most treatable, stage.