ctDNA Assay May Elucidate Outcomes With Chemo in HR+ Breast Cancer

Continuing to investigate how changing circulating tumor DNA (ctDNA) dynamics affect responses to chemotherapy across different timepoints may help with counseling and informing patients with hormone receptor–positive breast cancer, according to Stephanie L. Graff, MD in a conversation with CancerNetwork^®.

Graff, director of Breast Oncology at Lifespan Cancer Institute, spoke about findings from a pilot study assessing the feasibility of using the Signatera ctDNA assay among patients with hormone receptor–positive disease included in the phase 3 monarchE trial (NCT03155997). She said that the next steps may involve assessing ctDNA clearance across additional timepoints as part of an expanded monarchE patient cohort.

Findings presented at the 2023 San Antonio Breast Cancer Symposium (SABCS) highlighted ctDNA positivity in 5.6% at baseline in the pilot subset of patients who completed adjuvant chemotherapy. Additionally, disease recurrence occurred in 21% of patients who were persistently ctDNA negative, which suggested an opportunity to improve detection with the Signatera assay.

Transcript:

It’s important to remember that this is a pilot feasibility cohort. It’s really more about making sure that the assay is going to be usable in this analysis. Hormone receptor–positive, early-stage breast cancer is a new horizon for ctDNA. We will expand this into our full translational cohort for monarchE and try to better define how we can interpret ctDNA in [patients with] high-risk, early-stage breast cancer. It taught us both that there’s room for these assays to improve and that 21% of patients were persistently negative and faced disease recurrence anyway.

The next step is to analyze the full monarchE translational cohort, as well as the other time points where samples were collected, and try to get a sense of both how ctDNA dynamics change over different time points since 95% of the patients received chemotherapy. A time point of 0 may have a lower rate of ctDNA detection because patients often had just finished chemotherapy. We may see that 3 months or 6 months is more predictive of that baseline ctDNA. Patients from that point may clear for that 24-month prediction of response to treatment. Looking at how that response changes over time is going to be really helpful as we counsel and inform patients on the truth about what’s going on with their disease.

Reference

Loi S, Johnston S, Arteaga C, et al. Results from a pilot study exploring ctDNA detection using a tumor-informed assay in the monarchE trial of adjuvant abemaciclib with endocrine therapy in HR+, HER2-, node-positive, high-risk early breast cancer. Presented at the 2023 San Antonio Breast Cancer Symposium; December 5-9, 2023; San Antonio, TX; abstract PS06-01.