medwireNews: Circulating tumor (ct)DNA monitoring for minimal residual disease (MRD) can identify patients at risk for distant relapse more than 5 years after diagnosis of high-risk, stage II–III hormone receptor (HR)-positive breast cancer, research shows.
The CHiRP study was presented at the 2022 ASCO Annual Meeting in Chicago, Illinois, USA, by Marla Lipsyc-Sharf (Dana-Farber Cancer Institute, Boston, Massachusetts, USA) and simultaneously published in the Journal of Clinical Oncology.
“These data suggest that there may be a period in which MRD is detectable via ctDNA before overt, late breast cancer recurrences,” the investigators write.
“This will inform future studies of liquid biopsy to personalize treatment and prevent or delay late recurrence of early-stage breast cancer.”
Recognizing that detection of MRD via plasma ctDNA is associated with an increased risk for metastatic recurrence, the team analyzed ctDNA and associated outcomes in the late adjuvant setting for HR-positive, HER2-negative breast cancer at high risk for recurrence on the basis of T3–T4 or N2–N3 staging or T1–T2 plus at least three positive lymph nodes, or T2N1 plus a high-risk PAM50 score or similar, grade 3 disease, or a Ki-67 score of 20% or higher.
Overall, 83 patients had adequate archived tumor samples to allow DNA extraction for whole-exome sequencing and the creation of a personalized liquid biopsy assay for ctDNA detection, the researchers explain.
These individuals underwent initial plasma collection a median 8.4 years after diagnosis and were followed up for a median 2.0 years, with patients providing a median of two plasma samples each during routine clinical visits at 6–12-month intervals.
Overall, 10.0% of patients had a positive MRD result based on ctDNA during the study and this included all six (7.2%) of the patients who were diagnosed with metastatic recurrence in the gastric wall, bone, lung, and/or liver.
One (1.2%) patient was diagnosed with local recurrence to the chest wall without evidence of MRD, Lipsyc-Sharf et al report. Two MRD-positive patients were not diagnosed with clinical recurrence during the course of the study, one of whom has been lost to follow-up, they note.
ctDNA detection was therefore 85.7% sensitive for the detection of any clinical recurrence and 100% sensitive for detection of metastatic recurrence, with a specificity of 97.4% for both types of recurrence.
Noting that the median lead time from a positive ctDNA test to diagnosis of clinical recurrence was 12.4 months, the researchers suggest that this time frame “could allow for testing in clinical trials whether intervention to treat MRD improves patient outcomes.”
Discussing the findings in an accompanying editorial, Angela DeMichele (Perelman Center for Advanced Medicine, Philadelphia, Pennsylvania, USA) and co-authors say that further research is required to create “a contemporaneous radiographic gold standard” for MRD testing that can accurately determine the sensitivity, specificity, and lead time.
They also ponder whether ctDNA could be used to both identify the optimal window for intervention and secondary prevention of clinical recurrence, as well as potentially evaluating response to treatments.
“With multiple prospective interventional breast cancer trials now launched or launching, emerging data will help guide the development of this new potentially paradigm-shifting tool to deliver individualized curative systemic therapies,” the editorialists conclude.
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