TOPLINE

Circulating tumor DNA (ctDNA) detected via a tissue-free epigenomic assay approximately 2 years after adjuvant chemotherapy strongly predicts distant recurrence in patients with early-stage breast cancer. Among 313 patients, ctDNA was detected in 18 samples, with 94% of these patients subsequently developing distant recurrence at a median of 7.9 months after detection.

METHODOLOGY

• It remains unclear which patients with breast cancer may have asymptomatic metastatic disease and how many can achieve better disease control from local or systemic therapy. ctDNA serves as a biomarker for molecular residual disease (MRD) after treatment and is associated with a high risk for metastatic recurrence in breast cancer. Prior studies of tissue-free ctDNA detection in the MRD setting have been relatively limited, with emerging evidence supporting its feasibility and prognostic value.
• Researchers retrospectively analyzed plasma samples from 313 patients with stage I-III early breast cancer who participated in the SUCCESS-A phase 3 clinical trial in Germany, with samples collected approximately 2 years after completion of adjuvant chemotherapy.
• Participants had no evidence of disease recurrence at the time of sample collection, and plasma was analyzed using a tissue-free epigenomic ctDNA assay (Guardant Reveal) to detect MRD.
• Analysis employed a landmark approach based on the time of sample collection, with survival analyses performed to assess distant recurrence-free interval, recurrence-free interval, and overall survival. Sensitivity for distant recurrence was calculated within predefined 6-month intervals, and specificity was determined in patients without evidence of disease recurrence during follow-up.
• Patients had a median clinical follow-up of 66 months from surgery, with samples collected at a median of 28 months after adjuvant chemotherapy and 21.3 months before recurrence in patients who experienced disease relapse.

TAKEAWAY

• ctDNA positivity was strongly associated with significantly shorter distant recurrence-free interval (hazard ratio [HR], 33.3; P < .0001) and poorer overall survival (HR, 27.3; P < .0001).
• Sensitivity for distant recurrence in patients with samples collected within 1 year before recurrence was 73% (11 of 15), increasing to 86% (six of seven) for samples collected within 6 months of recurrence, with specificity of 99.6% (267 of 268) in nonrecurred patients.
• Among patients with metastatic recurrence, ctDNA detection rates varied by subtype: 29% (6 of 21) for hormone receptor-positive/HER2-negative patients, 63% (five of eight) for HER2-positive patients, and 75% (six of eight) for patients with triple-negative breast cancer.
• The positive predictive value for distant recurrence was 94.4% (17 of 18), with a negative predictive value of 92.9% (274 of 295).

IN PRACTICE

“Tissue-free detection of ctDNA 2 years after adjuvant chemotherapy was highly prognostic in an early-stage breast cancer cohort, and can be used to stratify patients with early-stage breast cancer at high risk for recurrence during follow-up who may benefit from early interventions,” wrote the authors of the study.

SOURCE

The study was led by Thomas W. P. Friedl, PhD, Department of Gynecology and Obstetrics, Ulm University Hospital, Ulm, Germany. It was published online on September 4 in JCO Precision Oncology.

LIMITATIONS

The study had relatively few patients with recurrence within each receptor subtype, limiting the ability to conduct certain exploratory subtype-specific analyses. The analysis was based on a single 2-year post-treatment timepoint to predict future recurrence, excluding patients who experienced recurrence within 2 years after surgery and potentially biasing the study toward the evaluation of more indolent tumors. The single timepoint analysis limits assessments of temporal patterns of postsurgical ctDNA levels and surveillance lead time variability. The SUCCESS-A trial predates many current treatment modalities in the early breast cancer setting, including cyclin-dependent kinase 4/6 inhibitors, checkpoint inhibitors, PARP inhibitors, and antibody-drug conjugates, so ctDNA results after adjuvant anthracycline-based chemotherapy might not fully represent today’s treatment landscape.

DISCLOSURES

The study received support from Sanofi-Aventis; AstraZeneca; Eli Lilly and Company; Novartis; Pfizer; Chugai Pharmaceutical Co., Ltd.; Wilex GmbH; Veridex; and Guardant Health. Friedl disclosed no relevant conflicts of interest. Peter A. Fasching, MD, reported receiving honoraria from Roche; Novartis; Pfizer; Daiichi Sankyo; Eisai Co., Ltd.; Merck Sharp & Dohme; AstraZeneca; Hexal; Eli Lilly and Company; Seagen; Agendia; and Gilead Sciences, and research funding from Novartis, BioNTech, Cepheid, Roche, and Pfizer. Derek Dustin, PhD, and Mingyang Cai, PhD, reported being employees of Guardant Health and holding stock ownership in the company. Additional disclosures are noted in the original article.

This article was created using several editorial tools, including AI, as part of the process. Human editors reviewed this content before publication.