全基因组测序支持ctDNA测序用于乳腺癌检测。

IF 56.7 1区医学 Q1 ONCOLOGY

Annals of Oncology Pub Date : 2025-02-04 DOI:10.1016/j.annonc.2025.01.021

I. Garcia-Murillas , C.W. Abbott , R.J. Cutts , S.M. Boyle , J. Pugh , K.C. Keough , B. Li , R.M. Pyke , F.C.P. Navarro , R.O. Chen , K. Dunne , C. Bunce , S.R.D. Johnston , A. Ring , S. Russell , A. Evans , A. Skene , I.E. Smith , N.C. Turner

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引用次数: 0

摘要

背景：基于循环肿瘤DNA （ctDNA）的分子残留病（MRD）检测提出了一种识别复发高风险患者的策略。在这里，我们用一个超灵敏的、基于全基因组测序的、肿瘤知情的ctDNA平台来分析早期乳腺癌患者。方法：我们分析了78例患者的617份血浆样本（中位数8份，范围2-14份）（23例TNBC， 35例HER2+， 18例HR+， 2例未知）。在治疗前诊断、新辅助化疗（NAC）第2周期、手术后新辅助治疗（如给予）、第一年每3个月、之后每6个月采集样本。使用NeXT个人MRD平台分析血浆DNA，这是一种肿瘤信息全基因组测序方法，可产生个性化的ctDNA测序面板，追踪每位患者的中位数1,451个变体。MRD检测与临床结果相关。结果：ctDNA的检测水平从百万分之2.19 （PPM）到204,900 PPM（中位数405 PPM）， 39%的ctDNA检测在超低范围内。结论：全基因组驱动的MRD分析检测乳腺癌复发，比临床复发提前很长时间，并且与无复发生存期密切相关。诊断时ctDNA检出率高于基于外显子组的肿瘤检测报告。

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Whole genome sequencing-powered ctDNA sequencing for breast cancer detection

Background

Circulating tumour DNA (ctDNA)-based detection of molecular residual disease (MRD) presents a strategy to identify patients at high risk of relapse. In this article, we profile early breast cancer patients with an ultrasensitive, whole genome sequencing (WGS)-based, tumour-informed ctDNA platform.

Materials and methods

We analysed 617 plasma samples (median 8, range 2-14) from 78 patients (23 triple-negative breast cancer, 35 human epidermal growth factor receptor 2-positive, 18 hormone receptor-positive, and 2 unknown). Samples were collected at diagnosis before therapy, cycle 2 of neoadjuvant chemotherapy, post-surgery after neoad’juvant therapy if administered, every 3 months during the first year, and every 6 months thereafter. Plasma DNA was analysed using the NeXT Personal MRD platform, a tumour-informed WGS approach to produce personalized ctDNA sequencing panels tracking a median of 1451 variants per patient. MRD detection was correlated with clinical outcomes.

Results

ctDNA was detected at levels ranging from 2.19 parts per million (PPM) to 204 900 PPM (median 405 PPM), with 39% of all ctDNA detections in the ultra-low range <100 PPM. Of patients with samples at diagnosis, 98% (49/50) had ctDNA detected before treatment. At a median follow-up of 76 months (range 5-118 months), detection of ctDNA was associated with high risk of future relapse (P < 0.0001; log-rank test) and shortened overall survival (P < 0.0001) with a median lead time from ctDNA detection to clinical relapse of 15 months (range 0.9-61.5 months). MRD was identified in 100% (11/11) of patients who relapsed, with a median level of ctDNA at first MRD detection of 13.1 PPM. No ctDNA-undetected patients relapsed throughout follow-up (64/64). Comparison with exome-powered MRD detection assays showed improved sensitivity and lead time.

Conclusions

A whole genome-powered MRD assay detected breast cancer relapse with a long lead time over clinical relapse, and was strongly associated with relapse-free survival. Rates of ctDNA detection at diagnosis were higher than those reported with exome-based tumour-informed assays.

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来源期刊

Annals of Oncology 医学-肿瘤学

CiteScore

63.90

自引率

1.00%

发文量

3712

审稿时长

2-3 weeks

期刊介绍： Annals of Oncology, the official journal of the European Society for Medical Oncology and the Japanese Society of Medical Oncology, offers rapid and efficient peer-reviewed publications on innovative cancer treatments and translational research in oncology and precision medicine. The journal primarily focuses on areas such as systemic anticancer therapy, with a specific emphasis on molecular targeted agents and new immune therapies. We also welcome randomized trials, including negative results, as well as top-level guidelines. Additionally, we encourage submissions in emerging fields that are crucial to personalized medicine, such as molecular pathology, bioinformatics, modern statistics, and biotechnologies. Manuscripts related to radiotherapy, surgery, and pediatrics will be considered if they demonstrate a clear interaction with any of the aforementioned fields or if they present groundbreaking findings. Our international editorial board comprises renowned experts who are leaders in their respective fields. Through Annals of Oncology, we strive to provide the most effective communication on the dynamic and ever-evolving global oncology landscape.