DESCRIPTION (provided by applicant): Monitoring for disease recurrence is an essential component of the clinical management of breast cancer patients. Currently, breast cancer recurrence is detected with imaging, which is expensive, carries a risk of radiation exposure, has limited sensitivity, and does not reveal the molecular changes that arise in recurrent tumors. Tumors shed DNA into the blood stream, and recent studies have demonstrated that circulating tumor DNA (ctDNA) is a promising non-invasive biomarker to detect disease recurrence. Academic research labs, including ours, are developing increasingly better methods to detect ctDNA by sequencing tumor-specific mutations in DNA isolated from patients' blood plasma. Despite compelling progress in the research arena, there are few commercial CLIA-certified laboratories developing tests for breast cancer ctDNA. This proposal leverages a collaborative partnership between an academic cancer genomics research lab, a commercial next- generation sequencing CLIA certified laboratory, medical oncologists in research and community hospital settings, an academic CAP-accredited biorepository, and a biospecimen company. Our goal is to deliver a clinical test that measures ctDNA in order to enable non-invasive monitoring for disease recurrence in breast cancer patients. The research team is ideally suited to translate the Patch PCR ctDNA assay from small-scale academic projects to a robust CLIA laboratory test. In Specific Aims 1 and 2 we will work closely to develop a test that utilizes cutting edge genomics research approaches, meets CLIA lab protocol requirements, and delivers information that is useful to physicians. In Specific Aim 3, to validate the test, we will perform the assay on breast cancer patients who are being monitored for recurrence and we will correlate the ctDNA measurements with diagnoses based on imaging. It is clear that ctDNA testing will be a valuable tool for oncologists and our goal is to deliver a clinical-grade ctDNA test to monitor patients for breast cancer disease recurrence.