This study evaluated the sensitivity of assaying tumor DNA circulating in the plasma to monitor breast cancer. This assay is compared with three other approaches: radiographic imaging, assay of cancer antigen 15-3 (CA 15-3) levels, and assay of circulating tumor cells. Breast cancer is the most common cancer and the leading cause of cancer-related death in women worldwide. 1 Metastatic breast cancer remains an incurable disease but is treatable by means of serial administration of endocrine, cytotoxic, or biologic therapies. The monitoring of treatment response is essential to avoid continuing ineffective therapies, to prevent unnecessary side effects, and to determine the benefit of new therapeutics. Treatment response is generally assessed with the use of serial imaging, but radiographic measurements often fail to detect changes in tumor burden. Therefore, there is an urgent need for biomarkers that measure tumor burden with high sensitivity . . .