Serial Postoperative Circulating Tumor DNA Assessment Has Strong Prognostic Value During Long-Term Follow-Up in...

Area of Science:

• Oncology
• Molecular Diagnostics
• Genomics

Background:

• Long-term monitoring of breast cancer patients post-surgery is crucial for detecting relapse.
• Current methods for relapse detection have limitations in sensitivity and timeliness.
• Personalized assays offer a novel approach to molecular monitoring.

Purpose of the Study:

• To evaluate the sensitivity of a personalized, tumor-informed circulating tumor DNA (ctDNA) assay (Signatera) for detecting molecular relapse in breast cancer patients.
• To assess the lead interval between ctDNA detection and clinical relapse.
• To determine the prognostic value of serial ctDNA assessment.

Main Methods:

• 156 breast cancer patients were monitored for up to 12 years post-surgery and chemotherapy.
• Semiannual blood samples were prospectively collected and retrospectively analyzed using ultradeep sequencing ctDNA assays.
• Assays were personalized based on primary tumor whole-exome sequencing data.

Main Results:

• The Signatera assay detected ctDNA in 30 of 34 relapsed patients (88.2% sensitivity), predicting relapse up to 38 months in advance (median 10.5 months).
• ctDNA positivity was significantly associated with shorter relapse-free and overall survival (P < .0001).
• Triple-negative breast cancer patients with relapse showed early ctDNA positivity, while non-relapsed patients remained negative.

Conclusions:

• Serial postoperative ctDNA assessment provides strong prognostic value and potential for earlier therapeutic intervention.
• ctDNA monitoring may be more effective than current clinical tests like cancer antigen 15-3.
• Serially negative ctDNA tests indicate superior clinical outcomes, offering reassurance to breast cancer patients.