Personalized ctDNA Testing and Late Recurrence in High-Risk HR-Positive, HER2-Negative Breast Cancer

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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

The content in this post has not been reviewed by the American Society of Clinical Oncology, Inc. (ASCO®) and does not necessarily reflect the ideas and opinions of ASCO®.