Expert Discusses Circulating Tumor DNA Monitoring for Early-Stage Breast Cancer

In an interview with Pharmacy Times at the 2023 San Antonio Breast Cancer Symposium, Mridula George, MD, associate program director of Breast Medical Oncology at Rutgers Cancer Institute of New Jersey, discusses the role of personalized circulating tumor DNA monitoring in predicting the response to neoadjuvant therapy for early-stage breast cancer. George explores how incorporating personalized circulating tumor DNA monitoring could influence overall treatment strategy and decision-making processes in the management of early-stage breast cancer.

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Q: How does personalized circulating tumor DNA monitoring contribute to predicting the response to neoadjuvant therapy in patients with early-stage breast cancer?

Mirdula George: Circulating tumor DNA are short DNA fragments that are broken off from a patient's tumor. When a patient's tumor cells are breaking apart, it releases the cellular contents including tumor DNA into the bloodstream. Circulating tumor DNA is a small component of cell-free DNA. It's about 0.4%, but with the advances in technology that we're seeing, we’re able to detect this tumor DNA in the neoadjuvant setting, adjuvant setting, as well as in the metastatic setting. This is a dynamic biomarker. The half-life of the tumor DNA is about an hour to 2 hours. But with the development and technology, we have tumor-informed assays and tumor-naive assays. Tumor informed assays are assays that are developed based on a patient's tumor, and this assay is then used to screen the patient's blood for circulating tumor DNA. If you detect circulating tumor DNA in a patient's blood, we’re then able to alter the treatments, and there are clinical trials evaluating how best to use this information for the management of patient’s breast cancer.

Q: What specific advancements or technologies enable pharmacists to effectively utilize this monitoring in tailoring therapy for individual patients with this cancer?

Mirdula George: At this time, there are many assays that are available for monitoring circulating tumor DNA, but none of them have been validated as standard of care. There is Medicare approval for certain assays, and providers are starting to use that based on early information they've been getting from clinical trials. There are clinical trials evaluating the role of circulating tumor DNA. So as health care providers and pharmacists enrolling patients on clinical trials that are looking at circulating tumor DNA, especially in the post adjuvant surveillance setting, would be helpful for patients and for advancing our knowledge in the setting.

Q: In what ways does incorporating personalized circulating tumor DNA monitoring impact the overall treatment strategy and decision-making process for the management of early-stage breast cancer?

Mirdula George: Circulating tumor DNA gives us more information than we previously had. It's able to detect micro-metastatic disease before patients have metastatic disease on imaging. It gives us this period where we could potentially intervene and see if we can alter the course of metastatic disease for the subgroup of patients. There are ongoing trials that are looking at how we can best use circulating tumor DNA [and] what are the direct targeted therapies that could be used potentially for patients. There's a lot of work being done, and we're still trying to understand how circulating tumor DNA can be incorporated with standard-of-care technologies that are drug therapies. But at this time, we're still trying to get information from ongoing clinical trials.

Q: What ongoing research or developments should pharmacists be aware of in this space, and how might these impact future practices in managing patients with early-stage breast cancer?

Mirdula George: There are multiple clinical trials going on evaluating different drugs, and as part of these clinical trials, the trial sponsors are looking at circulating tumor DNA to see how that changes. There are also clinical trials looking at interventions for patients who have circulating tumor DNA after they've completed those therapies for early-stage breast cancer, and they're trying to randomize patients into treatment versus no treatment to see if early intervention does alter the course of metastatic disease in these patients.