Personalized ctDNA monitoring in metastatic HR+/HER2- breast cancer patients during endocrine and CDK4/6 inhibitor therapy.

IF 7.6 2区医学 Q1 ONCOLOGY

NPJ Breast Cancer Pub Date : 2025-07-19 DOI:10.1038/s41523-025-00783-2

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

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Abstract

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.

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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

改进的方法来监测治疗反应可能会加强病人的管理和临床结果。本研究评估了在接受内分泌和CDK4/6抑制剂治疗的转移性HR+/HER2-乳腺癌患者中肿瘤通知循环肿瘤DNA （ctDNA）测定的可行性和性能。通过对档案肿瘤进行全外显子组测序，为血液监测设计了高度敏感的个性化ctDNA面板。该检测显示出较高的检测灵敏度（基线91%，所有时间点70%），并且在较高的基线估计变异等位基因分数、肝转移、较短的治疗失败时间（TTF）和总生存期（OS）之间存在关联。28%的患者观察到完全分子反应，定义为ctDNA清除，并与改善的TTF （HR 0.07）和OS （HR 0.07）相关。最后一个明确的时间点比治疗失败早14.3个月。ctDNA升高或有限的降低在x线摄影进展之前。分子计量学可以促进血浆优先监测和临床实践和试验设计的创新策略。

本文章由计算机程序翻译，如有差异，请以英文原文为准。

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来源期刊

NPJ Breast Cancer Medicine-Pharmacology (medical)

CiteScore

10.10

自引率

1.70%

发文量

122

审稿时长

9 weeks

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.