The ability to serially monitor tumor-derived cell-free DNA (cfDNA) brings with it the potential to measure response to anticancer therapies and detect minimal residual disease (MRD). This report describes a patient with HER2-positive metastatic breast cancer with an exceptional response to trastuzumab and nab-paclitaxel who remains in complete remission several years after cessation of therapy. Next-generation sequencing of the patient’s primary tumor tissue showed several mutations, including an oncogenic hotspot PIK3CA mutation. A sample of cfDNA was collected 6 years after her last therapy and then analyzed for mutant PIK3CA using digital PCR. No detectable mutations associated with the primary tumor were found despite assaying> 10,000 genome equivalents, suggesting that the patient had achieved a molecular remission. Results of this case study suggest that serial monitoring of MRD using liquid biopsies could provide a useful method for individualizing treatment plans for patients with metastatic disease with extreme responses to therapy. However, large-scale clinical studies are needed to validate and implement these techniques for patient care.

Precision oncology focuses on matching targeted therapies to genetic alterations in a patient’s tumor, usually in a metastatic setting. When responses to such treatments are seen, the long-term benefit remains uncommon. However, a minority of patients are “exceptional responders,” and although no standardized definition of this phenomenon has been established, sustained remissions or lack of progression spanning years to decades has generally characterized this cohort. Presentations vary widely, including stable disease for protracted periods and a few exceptional responders who demonstrate no evidence of metastatic disease even after cessation of antineoplastic therapies. Whether these patients are cured or harbor minimal residual disease (MRD) that may ultimately relapse is unknown.