ctDNA Monitoring in Breast Cancer Treatment: Early Signs and Future Directions

Tumor cell being attacked - Generated with Google Gemini AI

Circulating tumor DNA (ctDNA) is emerging as a valuable tool across many cancer types. One study (NCT05333874) sought to investigate the potential of ctDNA testing to track treatment response in breast cancer patients receiving neoadjuvant therapy.

In the study, ctDNA was detectable in most patients with both triple-negative and HER2-positive breast cancer. Higher pretreatment ctDNA levels were associated with larger tumors and more advanced stages.

Patients who cleared ctDNA within 6 weeks of neoadjuvant treatment were more likely to have a good surgical outcome. Postsurgical ctDNA positivity was more common in patients with higher pretreatment levels or advanced stage disease. In some cases, it even identified hidden metastases not detected by imaging.

Additionally, for 2 patients, ctDNA testing led to changes in treatment. One patient was due to persistent ctDNA after achieving a complete surgical response, and another was due to the identification of a hidden metastasis.

The findings of this study suggest that ctDNA monitoring during neoadjuvant can be a valuable tool for early assessment of treatment response and guiding postsurgical treatment decisions.

In an interview with Targeted Oncology^TM, Mridula George, MD, breast medical oncologist and associate director of breast medical oncology at Rutgers Cancer Institute, discussed the study, its implications, and the next steps in research for ctDNA in breast cancer.

Mridula George, MD

Targeted Oncology: What are some of the unmet needs in this patient population?

George: In patients with breast cancer, we have a lot of effective therapies. Despite the effects of the therapies, patients are still at risk of recurrence. Now, with the availability of circulating tumor DNA, it is helpful to know what the role of circulating tumor DNA would be in identifying patients who are at an increased risk of relapse.

What were you investigating in this study?

This was a prospective, single-institution study evaluating the role of circulating tumor DNA in patients with stage II and stage III triple-negative breast cancer and HER2-positive breast cancers. To be eligible, patients were evaluated to see if they had detectable circulating tumor DNA at the time of diagnosis prior to receiving any therapies. Patients that had detectable circulating tumor DNA were enrolled in the study, and circulating tumor DNA was monitored during the course of the study.We wanted to determine if detection of circulating tumor DNA in the post surgery setting would enable intervention and change patient outcomes.

Can you summarize your findings?

Thirty patients were enrolled in the study. The circulating tumor DNA levels were monitored while the patients were going through chemotherapy prior to having surgery. We noticed that, in the majority of the patients, circulating tumor DNA became undetectable within the first 6 weeks of treatment. But in the other 30% of patients, some still had delayed clearance, whereas other patients continued to be positive, despite the treatments that they were receiving at the time of prior surgery. In our group of 30 patients, 5patients relapsed with metastatic disease. Out of the 5, 3 of those patients were identified based on detectable circulating tumor DNA after surgery while we were monitoring them. Patients who did have relapsed metastatic disease did not have circulating tumor DNA, but their only site of disease was the brain.

Our hypothesis is that these patients have brain-only recurrence, so we were not able to pick up circulating tumor DNA in the peripheral blood because of the blood-brain barrier. One of the patients had a circulating tumor DNA that was detected after surgery, and we were able to change the treatment.Due to the change in treatment, we know her circulating tumor DNA became undetectable. She is currently off treatment, and she is doing well so far, given the change in intervention.

Based on these findings, are there any implications or takeaways for clinicians?

In the 5 patients who had recurrence, 1 thing that we noticed was that they had a higher level of detectable ctDNA at the time of diagnosis. We know that higher tumor size, higher nodal status, higher grade, those all increase the risk of relapse. Similarly, our hypothesis is that higher circulating tumor DNA levels also probably increase the risk of relapse. However, this is a small institutional study. We need larger data sets to determine what the levels of circulating tumor DNA would implicate in these patients.

What implications does using ctDNA have in predicting or monitoring progression or relapse?

Circulating tumor DNA currently is able to predict or identify patients who are at higher risk of relapse. The lead time is about 9 months depending on the subtype of breast cancer. We do not have any data regarding intervention in patients who have sort of detectable circulating tumor DNA. But the field is trying to identify, does early intervention reduce the risk of relapse in these patients with circulating tumor DNA, especially if the circulating tumor DNA becomes undetectable?

What are the next steps or the goals for further areas in this research?

In patients’ circulating tumor DNA, we need to understand what the right drug target is to use, and it is probably going to be unique for every patient. It is not going to be one size fits all. We need to find the right drug for the right subtype of breast cancer, and does changing the detectability to undetectable circulating tumor DNA levels change the outcome of that patient's breast cancer journey?

REFERENCE:

George M, Omene C, Kalashnikova E, et al. Predicting response to neoadjuvant therapy (NAT) in patients (pts) with early-stage breast cancer (BC) using circulating tumor DNA (ctDNA) testing. J Clin Oncol. 2024;42(suppl 16)abstr 569.doi:10.1200/JCO.2024.42.16_suppl.569