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Massimo Cristofanilli, MD, discusses the use of circulating tumor DNA for minimal residual disease detection in patients with breast cancer.
Massimo Cristofanilli, MD, attending physician, NewYork-Presbyterian Hospital; professor, medicine, Weill Cornell Medical College, Cornell University, discusses the use of circulating tumor DNA for minimal residual disease (MRD) detection in patients with breast cancer, as well as the role of tumor-informed biopsies in the monitoring and management of this disease.
Over the past decade, the field of liquid biopsy has advanced, transitioning from detecting circulating tumor cells for prognostic insights to designing more sensitive technologies capable of identifying tumor DNA mutations, Cristofanilli begins. These mutations have become critical targets for drug development, he says. Current treatment guidelines for patients with metastatic breast cancer recommend cell-free DNA testing to identify actionable mutations, such as PI3K, AKT, PTEN, HER2, and ESR1 mutations and amplifications, he notes. These alterations can be targeted by FDA-approved therapies, reflecting the value of cell-free DNA for informing treatment decision-making in the metastatic setting, he emphasizes.
Technological advancements have enhanced the sensitivity of liquid biopsies, allowing for early detection of disease before clinical symptoms emerge, Cristofanilli continues, adding that MRD detection is particularly relevant for high-risk patients. These include patients with triple-negative breast cancer who do not achieve a pathologic complete response following neoadjuvant therapy or patients with breast cancer with significant lymph node involvement, he states. Such patients face a high risk of disease recurrence within the first 2 to 3 years after surgery and radiation therapy, yet no standard imaging recommendations exist for routine surveillance in this patient population, he reports.
Two primary approaches are used for early detection of recurrence at the molecular level, Cristofanilli explains. The tumor-informed approach involves performing next-generation sequencing on resected or biopsied tumors to create a molecular signature, which is then monitored in the bloodstream through liquid biopsy, he says. A positive signal indicates either existing disease detectable by imaging or the likelihood of recurrence in the near future, he concludes.
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