Circulating Tumor DNA and Late Recurrence in High-Risk Hormone Receptor–Positive, Human Epidermal Growth Factor Receptor 2–Negative Breast Cancer

Journal of Clinical Oncology, Год журнала: 2022, Номер 40(22), С. 2408 - 2419

Опубликована: Июнь 4, 2022

To examine the prevalence and dynamics of circulating tumor DNA (ctDNA) its association with metastatic recurrence in patients high-risk early-stage hormone receptor-positive breast cancer (HR+ BC) more than 5 years from diagnosis.We enrolled 103 stage II-III HR+ BC diagnosed prior without clinical evidence recurrence. We performed whole-exome sequencing (WES) on primary tissue to identify somatic mutations tracked via a personalized, tumor-informed ctDNA test detect minimal residual disease (MRD). collected plasma at time consent routine visits every 6-12 months. Patients were followed for recurrence.In total, 85 had sufficient tissue; them, 83 (97.6%) successful sequencing. Personalized assays designed targeting median 36 variants 219 samples. The diagnosis first sample was 8.4 years. follow-up 10.4 2.0 sample. number samples per patient two. Eight (10%) positive MRD testing any point. Six (7.2%) developed distant recurrence, all whom MRD-positive before overt lead 12.4 not identified one (1.2%) local Two eight last follow-up.In this prospective study, late adjuvant setting, 1 year cases metastasis. Future studies will determine if ctDNA-guided intervention can alter outcomes.

Язык: Английский

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Use of ctDNA in early breast cancer: analytical validity and clinical potential

npj Breast Cancer, Год журнала: 2024, Номер 10(1)

Опубликована: Июнь 19, 2024

Abstract Circulating free tumor DNA (ctDNA) analysis is gaining popularity in precision oncology, particularly metastatic breast cancer, as it provides non-invasive, real-time information to complement tissue biopsies, allowing for tailored treatment strategies and improved patient selection clinical trials. Its use early cancer has been limited so far, due the relatively low sensitivity of available techniques a setting characterized by lower levels ctDNA shedding. However, advances sequencing bioinformatics, well methylome profiles, have led an increasing interest application from screening curative evaluation minimal residual disease (MRD) detection. With multiple prospective trials this setting, may become useful practice. This article reviews data regarding analytical validity currently tests detection potential cancer.

Язык: Английский

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High- or low-dose preoperative ipilimumab plus nivolumab in stage III urothelial cancer: the phase 1B NABUCCO trial

Nature Medicine, Год журнала: 2023, Номер 29(3), С. 588 - 592

Опубликована: Фев. 2, 2023

Язык: Английский

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Using cfDNA and ctDNA as Oncologic Markers: A Path to Clinical Validation

International Journal of Molecular Sciences, Год журнала: 2023, Номер 24(17), С. 13219 - 13219

Опубликована: Авг. 25, 2023

The detection of circulating tumor DNA (ctDNA) in liquid biopsy samples as an oncological marker is being used clinical trials at every step management. As ctDNA-based kits are developed and clinics, companies work towards increased convenience, accuracy, cost over solid biopsies other markers. technology to differentiate ctDNA cell-free (cfDNA) continues improve with new tests methodologies able detect down mutant allele frequencies 0.001% or 1/100,000 copies. Recognizing this development technology, the FDA has recently given pre-market approval breakthrough device designations multiple companies. purpose review look utility measuring total cfDNA, techniques from different using relevant articles PubMed, clinicaltrials.gov, approvals, company newsletters. Measuring cfDNA could be a cost-effective, viable prognostic marker, but various factors do not favor it monitoring tool during chemotherapy. While there may place clinic for future, lack standardization means that difficult move forward large-scale validation studies currently. promising standardized large ongoing, their applications screening minimal residual disease can suffer lower sensitivity. However, researchers working solutions these issues innovations multi-omics, sampling. With great promise, further research needed before recommended everyday

Язык: Английский

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Cell-free DNA approaches for cancer early detection and interception

Journal for ImmunoTherapy of Cancer, Год журнала: 2023, Номер 11(9), С. e006013 - e006013

Опубликована: Сен. 1, 2023

Rapid advancements in the area of early cancer detection have brought us closer to achieving goals finding enough treat or cure it, while avoiding harms overdiagnosis. We evaluate progress development tests context current principles for screening. review cell-free DNA (cfDNA)-based approaches using mutations, methylation, fragmentomes detection. Lastly, we discuss challenges demonstrating clinical utility these before integration into routine care.

Язык: Английский

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Personalized ctDNA for Monitoring Disease Status in Head and Neck Squamous Cell Carcinoma

Clinical Cancer Research, Год журнала: 2024, Номер 30(15), С. 3329 - 3336

Опубликована: Июнь 2, 2024

Many patients with locoregionally advanced human papillomavirus-negative head and neck squamous cell carcinoma (HNSCC) relapse. ctDNA has the potential to identify minimal residual disease, but its clinical utility for virus-negative HNSCC is not well understood.

Язык: Английский

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Bridging horizons beyond CIRCULATE-Japan: a new paradigm in molecular residual disease detection via whole genome sequencing-based circulating tumor DNA assay

International Journal of Clinical Oncology, Год журнала: 2024, Номер 29(5), С. 495 - 511

Опубликована: Март 29, 2024

Circulating tumor DNA (ctDNA) is the fraction of cell-free in patient blood that originates from a tumor. Advances sequencing technologies and our understanding molecular biology tumors have increased interest exploiting ctDNA to facilitate detection residual disease (MRD). Analysis as promising MRD biomarker solid malignancies has central role precision medicine initiatives exemplified by CIRCULATE-Japan project involving patients with resectable colorectal cancer. Notably, underscores prognostic significance status at 4 weeks post-surgery its correlation adjuvant therapy efficacy interim analysis. This substantiates hypothesis critical indicator relapse Despite remarkable advancements, challenges endure, primarily attributable exceedingly low concentration peripheral blood, particularly scenarios shedding intrinsic error rates current technologies. These complications necessitate more sensitive sophisticated assays verify clinical utility across all tumors. Whole genome (WGS)-based tumor-informed recently demonstrated ability detect parts-per-million range. review delineates landscape assays, highlighting WGS-based approaches forefront technique Additionally, it introduces upcoming endeavor, pan-cancer via ctDNA, forthcoming project, SCRUM-Japan MONSTAR-SCREEN-3.

Язык: Английский

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Detection of Circulating Tumor DNA in Liquid Biopsy: Current Techniques and Potential Applications in Melanoma

International Journal of Molecular Sciences, Год журнала: 2025, Номер 26(2), С. 861 - 861

Опубликована: Янв. 20, 2025

The treatment landscape for advanced melanoma has transformed significantly with the advent of BRAF and MEK inhibitors (BRAF/MEKi) targeting BRAFV600 mutations, as well immune checkpoint (ICI) like anti-PD-1 monotherapy or its combinations anti-CTLA-4 anti-LAG-3. Despite that, many patients still do not benefit from these treatments at all develop resistance mechanisms. Therefore, prognostic predictive biomarkers are needed to identify who should switch escalate their strategies initiate an intensive follow-up. In melanoma, liquid biopsy shown promising results, a potential role in predicting relapse resected high-risk disease monitoring during disease. Several components peripheral blood have been analyzed, such circulating tumor cells (CTCs), cell-free DNA (cfDNA), circulant tumoral (ctDNA), which turned out be particularly promising. To analyze ctDNA blood, different techniques proven useful, including digital droplet polymerase chain reaction (ddPCR) detect specific mutations and, more recently, next-generation sequencing (NGS) techniques, allow analyzing broader repertoire mutation each patient. this review, our goal is update current understanding biopsy, focusing on use biological material daily clinical management patients, particular those treated ICI.

Язык: Английский

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What the clinician needs to know about laboratory analyses of circulating tumor DNA

Clinical Colorectal Cancer, Год журнала: 2025, Номер unknown

Опубликована: Янв. 1, 2025

Язык: Английский

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Molecular residual disease analysis of adjuvant osimertinib in resected EGFR-mutated stage IB–IIIA non-small-cell lung cancer

Nature Medicine, Год журнала: 2025, Номер unknown

Опубликована: Март 17, 2025

Osimertinib—a third-generation epidermal growth factor receptor-tyrosine kinase inhibitor—is recommended as adjuvant therapy for resected stage IB–IIIA receptor-mutated non-small-cell lung cancer, based on significant disease-free survival (DFS) and overall improvement shown in the previously reported phase 3 ADAURA trial. A trend toward an increased DFS event rate after completion of years treatment suggests that some patients may benefit from longer osimertinib treatment. We therefore explored whether tumor-informed, circulating tumor DNA-based, molecular residual disease (MRD) could predict recurrence exploratory post hoc analysis 220 (n = 112 osimertinib; n 108 placebo) ADAURA. MRD preceded imaging events this study by a median 4.7 (95% confidence interval, 2.2–5.6) months. event-free at 36 months was 86% versus 36% placebo groups (hazard ratio, 0.23 0.15–0.36)). In group, or were detected 28 (25%) patients; most occurred following cessation (19 28, 68%) within 12 stopping (11 19, 58%). At 24 osimertinib, 66%. study, across both arms. status maintained during posttreatment follow-up, with occurring discontinuation completion. detection potentially identify who although requires clinical confirmation. ClinicalTrials.gov identifier: NCT02511106 . Exploratory trial EGFR-mutated cancer shows predicts long-term

Язык: Английский

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