The Promise of ctDNA in Triple-Negative Breast Cancer

By: Amanda Brink, DNP, APRN, FNP-BC, AOCNP

From: cancernursingtoday.com

Patients and providers alike are becoming increasingly interested in the role of circulating tumor DNA (ctDNA) in predicting response to cancer treatment and assessing the risk of relapse. Although ctDNA is not yet routinely used in clinical practice for most patients with breast cancer, it holds significant promise, particularly in aggressive subtypes such as triple-negative breast cancer (TNBC). In these cases, early detection of progression or recurrence could help guide treatment decisions. Oncology nurses play a key role in supporting patients as they navigate this evolving area of precision oncology and helping them understand both the test results and their potential implications.

ctDNA as a Biomarker in Immunotherapy

In a recent review, Dr. Sudhir Kumar and Dr. Rossanna Pezo explore the current and potential uses of ctDNA in breast cancer treated with immunotherapy, with a focus on TNBC. ctDNA refers to fragments of DNA that are shed from cancer cells into the bloodstream and can be analyzed using next-generation sequencing (NGS). Compared with tissue biopsies, ctDNA testing offers several advantages: it is minimally invasive and allows for real-time monitoring over the course of treatment.

Commercial ctDNA assays vary in their approach. Some are “tumor-informed,” meaning they are customized based on specific mutations identified from a patient’s tumor tissue. Others are “tumor-agnostic,” using a standardized panel of genetic alterations to look for cancer-related changes without needing prior tumor sequencing. Both approaches offer benefits, but each has limitations.

Despite its promise, clinical implementation of ctDNA testing still faces barriers. Sensitivity can vary depending on the amount of ctDNA present, which is typically smaller in early-stage disease, raising the risk of false-negative results. In addition, false-positive results can occur due to clonal hematopoiesis, a common age-related process in which blood cells acquire mutations unrelated to cancer.

The review highlights that in TNBC, ctDNA levels are generally higher than in other breast cancer subtypes, which may make detection more reliable. Importantly, ctDNA may help identify patients who are more likely to respond to immunotherapy or experience disease recurrence. Early signals suggest that changes in ctDNA levels during treatment may correlate with treatment response. In some studies, clearance of ctDNA has been associated with improved progression-free and overall survival. Conversely, persistent or rising ctDNA may signal resistance or early relapse, prompting consideration of treatment modification or intensified surveillance.

For patients receiving neoadjuvant immunotherapy, ctDNA can potentially guide decisions about the need for additional therapy after surgery. Postoperative ctDNA detection has been associated with worse outcomes and may offer a way to identify minimal residual disease before radiographic or clinical evidence of recurrence appears.

Although promising, the use of ctDNA to guide immunotherapy decisions in breast cancer remains investigational. Many of the existing studies are limited by small sample sizes, retrospective designs, and heterogeneous treatment regimens. Larger, prospective clinical trials are underway to validate these findings and determine how to best integrate ctDNA into clinical care.

Researchers are actively exploring how ctDNA might help identify patients who are at higher risk for experiencing immune-related side effects from immunotherapy, which could allow for earlier interventions or closer monitoring. Another promising area of investigation involves combining ctDNA data with imaging-based information (radiomics) and clinical characteristics to create more accurate tools for predicting how a patient’s disease may progress and how they might respond to treatment.

In addition, ctDNA may help distinguish pseudoprogression, which is a temporary increase in tumor size due to immune cell infiltration, from true disease progression, which remains a challenge in interpreting responses to immunotherapy.

Nursing Considerations

Oncology nurses play a central role in helping patients understand what ctDNA testing is and both the benefits and limitations of this testing. Nurses are often the ones answering questions about new technologies and helping patients interpret results. As ctDNA becomes more integrated into clinical care, oncology nurses can make a significant impact on patient care by providing the most up-to-date information about this technology.