Jesús Fuentes-Antrás, Mitchell J Elliott, Sasha C Main, Philippe Echelard, Aaron Dou, Philippe L Bedard, Eitan Amir, Michelle B Nadler, Nicholas Meti, Nancy Gregorio, Elizabeth Shah, Emily Van de Laar, Celeste Yu, Yangqing Deng, Lisa Gates, Clodagh Murray, Christopher G Smith, Amber Chevalier, Scott V Bratman, Lillian L Siu, Hal K Berman, David W Cescon
{"title":"在内分泌和CDK4/6抑制剂治疗期间转移性HR+/HER2-乳腺癌患者的个性化ctDNA监测","authors":"Jesús Fuentes-Antrás, Mitchell J Elliott, Sasha C Main, Philippe Echelard, Aaron Dou, Philippe L Bedard, Eitan Amir, Michelle B Nadler, Nicholas Meti, Nancy Gregorio, Elizabeth Shah, Emily Van de Laar, Celeste Yu, Yangqing Deng, Lisa Gates, Clodagh Murray, Christopher G Smith, Amber Chevalier, Scott V Bratman, Lillian L Siu, Hal K Berman, David W Cescon","doi":"10.1038/s41523-025-00783-2","DOIUrl":null,"url":null,"abstract":"<p><p>Improved methods to monitor treatment response may enhance patient management and clinical outcomes. This study assessed the feasibility and performance of a tumor-informed circulating tumor DNA (ctDNA) assay in metastatic HR+/HER2- breast cancer patients receiving endocrine and CDK4/6 inhibitor therapy. By conducting whole exome sequencing on archival tumors, highly sensitive personalized ctDNA panels were designed for blood monitoring. The assay showed high detection sensitivity (91% baseline, 70% all timepoints) and associations between higher baseline estimated variant allele fractions, liver metastases, and shorter time to treatment failure (TTF) and overall survival (OS). Complete molecular response, defined as ctDNA clearance, was observed in 28% of patients and correlated with improved TTF (HR 0.07) and OS (HR 0.07). The last cleared timepoint predated treatment failure by a median 14.3 months. ctDNA rises or limited decreases preceded radiographic progression. Molecular metrics may facilitate plasma-first monitoring and innovative strategies for clinical practice and trial design.</p>","PeriodicalId":19247,"journal":{"name":"NPJ Breast Cancer","volume":"11 1","pages":"74"},"PeriodicalIF":7.6000,"publicationDate":"2025-07-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12276344/pdf/","citationCount":"0","resultStr":"{\"title\":\"Personalized ctDNA monitoring in metastatic HR+/HER2- breast cancer patients during endocrine and CDK4/6 inhibitor therapy.\",\"authors\":\"Jesús Fuentes-Antrás, Mitchell J Elliott, Sasha C Main, Philippe Echelard, Aaron Dou, Philippe L Bedard, Eitan Amir, Michelle B Nadler, Nicholas Meti, Nancy Gregorio, Elizabeth Shah, Emily Van de Laar, Celeste Yu, Yangqing Deng, Lisa Gates, Clodagh Murray, Christopher G Smith, Amber Chevalier, Scott V Bratman, Lillian L Siu, Hal K Berman, David W Cescon\",\"doi\":\"10.1038/s41523-025-00783-2\",\"DOIUrl\":null,\"url\":null,\"abstract\":\"<p><p>Improved methods to monitor treatment response may enhance patient management and clinical outcomes. This study assessed the feasibility and performance of a tumor-informed circulating tumor DNA (ctDNA) assay in metastatic HR+/HER2- breast cancer patients receiving endocrine and CDK4/6 inhibitor therapy. By conducting whole exome sequencing on archival tumors, highly sensitive personalized ctDNA panels were designed for blood monitoring. The assay showed high detection sensitivity (91% baseline, 70% all timepoints) and associations between higher baseline estimated variant allele fractions, liver metastases, and shorter time to treatment failure (TTF) and overall survival (OS). Complete molecular response, defined as ctDNA clearance, was observed in 28% of patients and correlated with improved TTF (HR 0.07) and OS (HR 0.07). The last cleared timepoint predated treatment failure by a median 14.3 months. ctDNA rises or limited decreases preceded radiographic progression. Molecular metrics may facilitate plasma-first monitoring and innovative strategies for clinical practice and trial design.</p>\",\"PeriodicalId\":19247,\"journal\":{\"name\":\"NPJ Breast Cancer\",\"volume\":\"11 1\",\"pages\":\"74\"},\"PeriodicalIF\":7.6000,\"publicationDate\":\"2025-07-19\",\"publicationTypes\":\"Journal Article\",\"fieldsOfStudy\":null,\"isOpenAccess\":false,\"openAccessPdf\":\"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12276344/pdf/\",\"citationCount\":\"0\",\"resultStr\":null,\"platform\":\"Semanticscholar\",\"paperid\":null,\"PeriodicalName\":\"NPJ Breast Cancer\",\"FirstCategoryId\":\"3\",\"ListUrlMain\":\"https://doi.org/10.1038/s41523-025-00783-2\",\"RegionNum\":2,\"RegionCategory\":\"医学\",\"ArticlePicture\":[],\"TitleCN\":null,\"AbstractTextCN\":null,\"PMCID\":null,\"EPubDate\":\"\",\"PubModel\":\"\",\"JCR\":\"Q1\",\"JCRName\":\"ONCOLOGY\",\"Score\":null,\"Total\":0}","platform":"Semanticscholar","paperid":null,"PeriodicalName":"NPJ Breast Cancer","FirstCategoryId":"3","ListUrlMain":"https://doi.org/10.1038/s41523-025-00783-2","RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":null,"EPubDate":"","PubModel":"","JCR":"Q1","JCRName":"ONCOLOGY","Score":null,"Total":0}
Personalized ctDNA monitoring in metastatic HR+/HER2- breast cancer patients during endocrine and CDK4/6 inhibitor therapy.
Improved methods to monitor treatment response may enhance patient management and clinical outcomes. This study assessed the feasibility and performance of a tumor-informed circulating tumor DNA (ctDNA) assay in metastatic HR+/HER2- breast cancer patients receiving endocrine and CDK4/6 inhibitor therapy. By conducting whole exome sequencing on archival tumors, highly sensitive personalized ctDNA panels were designed for blood monitoring. The assay showed high detection sensitivity (91% baseline, 70% all timepoints) and associations between higher baseline estimated variant allele fractions, liver metastases, and shorter time to treatment failure (TTF) and overall survival (OS). Complete molecular response, defined as ctDNA clearance, was observed in 28% of patients and correlated with improved TTF (HR 0.07) and OS (HR 0.07). The last cleared timepoint predated treatment failure by a median 14.3 months. ctDNA rises or limited decreases preceded radiographic progression. Molecular metrics may facilitate plasma-first monitoring and innovative strategies for clinical practice and trial design.
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.
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