Dr Graff on the Relation Between ctDNA Positivity and Disease Recurrence in HR+/HER2– Breast Cancer

Stephanie L. Graff, MD, director, breast oncology, Lifespan Cancer Institute, assistant professor of medicine, Warren Alpert Medical School, co-leader, Breast Cancer Translational Research Disease Group, Brown University’s Legorreta Cancer Center, discusses findings from a pilot study exploring the association between disease recurrence and circulating tumor DNA (ctDNA) positivity in patients with hormone receptor (HR)–positive, HER2-negative, node-positive, high-risk, early breast cancer who have received adjuvant treatment of abemaciclib (Verzenio) and endocrine therapy.

This pilot study aimed to assess the technical feasibility of ctDNA detection using the Signatera™ assay in a subset of patients from the phase 3 monarchE trial (NCT03155997). The study analyzed samples from 178 patients, 84 of whom had been treated with abemaciclib and endocrine therapy, Graff begins. Although the study was enriched for invasive disease-free survival (IDFS) events, patients who experienced an IDFS event within the 2-year treatment window were ineligible for enrollment, she explains. Patients who received adjuvant chemotherapy and began endocrine therapy prior to randomization were included on the study.

Primary tumors from these patients underwent whole exome sequencing, providing a comprehensive genomic profile. The Signatera ctDNA assay was developed for each patient based on up to 16 variants detected by whole exome sequencing from the baseline tumor sample, Gradd states. The ctDNA detection aimed to assess the presence and clearance of ctDNA during and after treatment.

Results presented at the 2023 San Antonio Breast Cancer Symposium elucidated disease recurrence dynamics, she continues. Among the 10 patients who were ctDNA-positive at baseline, 42 became positive at 24 months, and all patients experienced disease recurrence. Three of the 108 patients who did not experience disease recurrence were ctDNA-positive at baseline. Persistence of ctDNA positivity from baseline to 24 months was observed in 7 patients, with a median duration of 27 months (range, 25-43) from baseline to recurrence, Graff elucidates.

Additionally, 35 patients became ctDNA-positive at 24 months, all of whom experienced an IDFS event after a median of 5 months prior to disease recurrence. The median duration of ctDNA detection at baseline to disease recurrence was 3 months (range, 1-19) in patients who remained ctDNA positive at 24 months, she expands

Overall, results from this study validated the feasibility of the Signatera assay, and potential prognostic significance of ctDNA detection in patients with HR–positive, HER2-negative breast cancer in the adjuvant setting. This pilot study is integral for understanding the technical aspects and utility of ctDNA detection as a potential biomarker for monitoring treatment response and disease recurrence in patients with high-risk early breast, receiving adjuvant abemaciclib and endocrine therapy. Results from the analysis may contribute to ongoing precision medicine efforts in breast cancer and improve long-term outcomes through innovative approaches like ctDNA monitoring.