Whole genome sequencing powered ctDNA sequencing for breast cancer detection.

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

Abstract

Background: Circulating tumour DNA (ctDNA) based detection of Molecular Residual Disease (MRD) presents a strategy to identify patients at high risk of relapse. Here we profile early breast cancer patients with an ultrasensitive, whole genome sequencing-based, tumour-informed ctDNA platform.

Methods: We analysed 617 plasma samples (median 8, range 2-14) from 78 patients (23 TNBC, 35 HER2+, 18 HR+ and 2 unknown). Samples were collected at diagnosis before therapy, cycle 2 of neoadjuvant chemotherapy (NAC), post-surgery after neoadjuvant 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 whole-genome sequencing approach to produce personalised ctDNA sequencing panels tracking a median of 1,451 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 prior to treatment. At a median follow-up of 76 months (range 5-118), detection of ctDNA associated with high risk of future relapse (p<0.0001; log-rank test) and shortened overall survival (p<0.0001) with median lead-time from ctDNA detection to clinical relapse of 15 months (range 0.9-61.5). 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 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.