Sao Trung Nguyen, Van-Anh Nguyen Hoang, Vu Nguyen Trieu, Thanh Huyen Pham, Thi Cuc Dinh, Dinh Hoang Pham, Ngoc Nguyen, Dao Nguyen Vinh, Thanh Thuy Thi Do, Duy Sinh Nguyen, Hoai-Nghia Nguyen, Hoa Giang, Lan N Tu
{"title":"Personalized mutation tracking in circulating-tumor DNA predicts recurrence in patients with high-risk early breast cancer.","authors":"Sao Trung Nguyen, Van-Anh Nguyen Hoang, Vu Nguyen Trieu, Thanh Huyen Pham, Thi Cuc Dinh, Dinh Hoang Pham, Ngoc Nguyen, Dao Nguyen Vinh, Thanh Thuy Thi Do, Duy Sinh Nguyen, Hoai-Nghia Nguyen, Hoa Giang, Lan N Tu","doi":"10.1038/s41523-025-00778-z","DOIUrl":null,"url":null,"abstract":"<p><p>The clinical utilization of circulating tumor DNA (ctDNA) in breast cancer (BC) management is not well-defined. In this prospective study, 168 patients with early-stage BC were recruited, serial blood samples were collected before and after surgery. Tumor-informed ctDNA testing was performed, which sequenced tumors for 95 genes followed by bespoke mPCR to track 1-9 mutations in the plasma. ctDNA was detected before surgery in 14.6%, 40.0%, 83.8%, and 80.0% of HR+ low-risk, HR+ high-risk, HR-HER2+ and HR-HER2- patients, respectively. Pre-operative ctDNA positivity was significantly associated with decreased disease-free survival (DFS) (adjusted HR = 3.09, 95% CI 2.65-80.0, p = 0.001). After a median 26.6-month follow-up, 11 patients relapsed, and ctDNA at landmark time point 2-4 weeks after surgery was detected in 50.0% (5/10) of cases. Landmark ctDNA clearance was associated with significantly longer DFS (p = 0.0009) and positive ctDNA persistence after adjuvant therapy occurred in 36.4% (4/11) of stage-III patients. During surveillance, ctDNA detection had 90.9% sensitivity and 98.8% specificity to predict recurrence, and median lead time of 9.7 months. Patients with detected ctDNA had shorter DFS than those with undetectable ctDNA (adjusted HR = 207.05, 95% CI 41.38- > 1000, p = 0.001). Therefore, ctDNA status both before and after surgery could help stratify recurrence risk for BC patients.</p>","PeriodicalId":19247,"journal":{"name":"NPJ Breast Cancer","volume":"11 1","pages":"58"},"PeriodicalIF":7.6000,"publicationDate":"2025-06-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12181414/pdf/","citationCount":"0","resultStr":null,"platform":"Semanticscholar","paperid":null,"PeriodicalName":"NPJ Breast Cancer","FirstCategoryId":"3","ListUrlMain":"https://doi.org/10.1038/s41523-025-00778-z","RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":null,"EPubDate":"","PubModel":"","JCR":"Q1","JCRName":"ONCOLOGY","Score":null,"Total":0}
引用次数: 0
Abstract
The clinical utilization of circulating tumor DNA (ctDNA) in breast cancer (BC) management is not well-defined. In this prospective study, 168 patients with early-stage BC were recruited, serial blood samples were collected before and after surgery. Tumor-informed ctDNA testing was performed, which sequenced tumors for 95 genes followed by bespoke mPCR to track 1-9 mutations in the plasma. ctDNA was detected before surgery in 14.6%, 40.0%, 83.8%, and 80.0% of HR+ low-risk, HR+ high-risk, HR-HER2+ and HR-HER2- patients, respectively. Pre-operative ctDNA positivity was significantly associated with decreased disease-free survival (DFS) (adjusted HR = 3.09, 95% CI 2.65-80.0, p = 0.001). After a median 26.6-month follow-up, 11 patients relapsed, and ctDNA at landmark time point 2-4 weeks after surgery was detected in 50.0% (5/10) of cases. Landmark ctDNA clearance was associated with significantly longer DFS (p = 0.0009) and positive ctDNA persistence after adjuvant therapy occurred in 36.4% (4/11) of stage-III patients. During surveillance, ctDNA detection had 90.9% sensitivity and 98.8% specificity to predict recurrence, and median lead time of 9.7 months. Patients with detected ctDNA had shorter DFS than those with undetectable ctDNA (adjusted HR = 207.05, 95% CI 41.38- > 1000, p = 0.001). Therefore, ctDNA status both before and after surgery could help stratify recurrence risk for BC patients.
期刊介绍:
npj Breast Cancer publishes original research articles, reviews, brief correspondence, meeting reports, editorial summaries and hypothesis generating observations which could be unexplained or preliminary findings from experiments, novel ideas, or the framing of new questions that need to be solved. Featured topics of the journal include imaging, immunotherapy, molecular classification of disease, mechanism-based therapies largely targeting signal transduction pathways, carcinogenesis including hereditary susceptibility and molecular epidemiology, survivorship issues including long-term toxicities of treatment and secondary neoplasm occurrence, the biophysics of cancer, mechanisms of metastasis and their perturbation, and studies of the tumor microenvironment.