In a study presented at the 2022 ASCO Annual Meeting (Abstract 103) and simultaneously reported in the Journal of Clinical Oncology, Lipsyc-Sharf et al found that personalized circulating tumor DNA (ctDNA) testing was successful in detecting measurable residual disease (MRD) prior to late clinical metastatic recurrence in women with high-risk hormone receptor (HR)-positive, HER2-negative breast cancer.
Between March 2018 and December 2020, the study enrolled 103 patients at Dana-Farber Cancer Institute with a history of stage II or III disease diagnosed at least 5 years prior to entry and no known cancer recurrence. Whole-exome sequencing was performed on primary tumor tissue to identify somatic mutations that were tracked using a personalized, tumor-informed ctDNA test to detect MRD. Plasma was collected at study entry and at routine visits every 6 to 12 months, and patients were followed for clinical recurrence.
Key Findings
Among the 103 patients, 85 had sufficient tumor tissue for whole-exome sequencing and 83 had successful whole-exome sequencing. Personalized ctDNA assays targeting a median of 36 pathogenic variants were used to test 219 plasma samples. Patients had a median of two plasma samples; median time from diagnosis to first sample was 8.4 years, and median follow-up was 10.4 years from diagnosis and 2.0 years from first plasma sample.
A total of eight patients (10%) had positive MRD testing at any time during follow-up. Of these, six developed distant metastatic recurrence at a median of 12.4 months after positive MRD testing. The remaining two patients were free of clinical recurrence at last follow-up.
MRD was not detected in one patient who developed local recurrence.
The investigators concluded, “In this prospective study, in patients with high-risk HR-positive breast cancer in the late adjuvant setting, ctDNA was identified a median of 1 year before all cases of distant metastasis. Future studies will determine if ctDNA-guided intervention in patients with HR-positive breast cancer can alter clinical outcomes.”
Heather A. Parsons, MD, MPH, of Dana-Farber Cancer Institute, is the corresponding author for the Journal of Clinical Oncology article.
Disclosure: The study was supported by Susan G. Komen, National Cancer Institute, and AstraZeneca. For full disclosures of the study authors, visit ascopubs.org.
