A Validation Study of a Multiple Reaction Monitoring-Based Proteomic Assay to Diagnose Breast Cancer

PURPOSE: Currently, the standard screening tool for breast cancer is screening mammography. There have been many efforts to develop a blood-based diagnostic assay for breast cancer diagnosis; however, none have been approved for clinical use at this time. The purpose of this study was to determine the accuracy of a novel blood-based proteomic test for aiding breast cancer diagnosis in a relatively large cohort of cancer patients. METHODS: A blood-based test using multiple reaction monitoring (MRM) measured by mass spectrometry to quantify 3 peptides (apolipoprotein C-1, carbonic anhydrase 1, and neural cell adhesion molecule L1-like protein) present in human plasma was investigated. A total of 1,129 blood samples from 575 breast cancer patients, 454 healthy controls, and 100 patients with other malignancies were used to verify and optimize the assay. RESULTS: The diagnostic sensitivity, specificity, and accuracy of the MRM-based proteomic assay were 71.6%, 85.3%, and 77%, respectively; the area under the receiver operating characteristic curve was 0.8323. The proteomic assay did not demonstrate diagnostic accuracy in patients with other types of malignancies including thyroid, pancreatic, lung, and colon cancers. The diagnostic performance of the proteomic assay was not associated with the timing of blood sampling before or after anesthesia. CONCLUSION: The data demonstrated that an MRM-based proteomic assay that measures plasma levels of three specific peptides can be a useful tool for breast cancer screening and its accuracy is cancer-type specific.