Measurement of Circulating Cell-Free DNA Levels by a Simple Fluorescent Test in Patients With Breast Cancer

Agassi, Ravit; Czeiger, David; Shaked, Gad; Avriel, Avital; Sheynin, Jony; Lavrenkov, Konstantin; Ariad, Samuel; Douvdevani, Amos

doi:10.1309/ajcpi5yhg0ogfahm

Cited by 58 publications

(50 citation statements)

References 20 publications

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“…This is the fourth study based on our innovative and simple technique to measure CFD levels in cancer patients [17][18][19]. Various complex techniques have been used to evaluate CFD concentrations, fragmentation, mutations, and epigenetic changes in cancer patients, including RCC.…”

Section: Discussionmentioning

confidence: 99%

Circulating Cell-Free DNA Levels in Patients with Metastatic Renal Cell Carcinoma

et al. 2017

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Background: Limited data about biomarkers are available to predict the outcomes of targeted therapy in metastatic renal cell carcinoma (mRCC). Circulating cell-free DNA (CFD) is elevated in various cancers. Patients and Methods: We performed a prospective study of patients with mRCC who received targeted therapy in the Soroka Medical Center between 2013 and 2015. CFD levels were measured using a simple fluorometric assay. Blood samples for CFD were collected before treatment and at weeks 1, 4, 12, 18, and 24 of treatment. The normal cut-off level of CFD was defined as 800 ng/ml. The association of CFD with objective response, progression-free survival (PFS), and overall survival was tested, with adjustment for known confounding risk factors. Results: A total of 23 patients were included; 18 were treated with first-line therapy and 5 with second- and third-line therapies. Patients with normal pretreatment CFD level had a better PFS versus patients with increased levels (p = 0.023). In multivariate analysis, factors associated with PFS were pretreatment CFD levels (p = 0.020) and Heng risk (p = 0.006). Conclusions: Elevated pretreatment CFD levels measured using a simple fluorometric assay may be associated with a worse PFS in patients with mRCC. A larger prospective study is warranted in order to validate our observation.

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Section: Discussionmentioning

confidence: 99%

Circulating Cell-Free DNA Levels in Patients with Metastatic Renal Cell Carcinoma

et al. 2017

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“…DNA amplification), however, its diagnostic value is suboptimal. In one study, its sensitivity and specificity in detecting early stage breast cancer were measured at 72% and 75%, respectively; this was described as higher than other common biomarkers but lower than the more expensive sequencing methods [52]. In a more recent study, sensitivity and specificity of array-based genome-wide DNA methylation testing in ctDNA samples obtained in early stage breast cancer was 86.2% and 82.7%, respecitvely.…”

Section: Methods For Measuring Ctdnamentioning

confidence: 99%

“…Multiple studies have documented an elevated level of ctDNA in patients with breast tumors and its direct correlation with tumor burden [17,33,52,56–61]. Levels of ctDNA drop after the resection of primary tumor [52,59].…”

Section: Diagnostic Threshold Of Ctdna Concentrationmentioning

confidence: 99%

“…Levels of ctDNA drop after the resection of primary tumor [52,59]. Table 1 provides a summary of these studies.…”

Section: Diagnostic Threshold Of Ctdna Concentrationmentioning

confidence: 99%

“…Several studies have shown that plasma levels of ctDNA are significantly higher in those who had higher stages of breast cancer, nodal involvement or larger tumors [38,52], and a recent study showed an association with overal survival as well [80]. However, more evidence is needed to establish the prognostic value of ctDNA concentration in breast cancer patients.…”

Section: Monitoring Disease Progressionmentioning

confidence: 99%

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Analysis of circulating tumor DNA in breast cancer as a diagnostic and prognostic biomarker

Rohanizadegan

2018

Cancer Genetics

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Despite all the advances in diagnosis and treatment of breast cancer, a large number of patients suffer from late diagnosis or recurrence of their disease. Current available imaging modalities do not reveal micrometastasis and tumor biopsy is an invasive method to detect early stage or recurrent cancer, signifying the need for an inexpensive, non-invasive diagnostic modality. Cell-free tumor DNA (ctDNA) has been tried for early detection and targeted therapy of breast cancer, but its diagnostic and prognostic utility is still under investigation. This review summarizes the existing evidence on the use of ctDNA specifically in breast cancer, including detection methods, diagnostic accuracy, role in genetics and epigenetics evaluation of the tumor, and comparison with other biomarkers. Current evidence suggests that increasing levels of ctDNA in breast cancer can be of significant diagnostic value for early detection of breast cancer although the sensitivity and specificity of the methods is still suboptimal. Additionally, ctDNA allows for characterizing the tumor in a non-invasive way and monitor the response to therapy, although discordance of ctDNA results with direct biopsy (i.e. due to tumor heterogeneity) is still considered a notable limitation.

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Clinical applications of next‐generation sequencing‐based ctDNA analyses in breast cancer: defining treatment targets and dynamic changes during disease progression

Klocker,

Hasenleithner,

Bartsch

et al. 2024

Molecular Oncology

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The advancements in the detection and characterization of circulating tumor DNA (ctDNA) have revolutionized precision medicine and are likely to transform standard clinical practice. The non‐invasive nature of this approach allows for molecular profiling of the entire tumor entity, while also enabling real‐time monitoring of the effectiveness of cancer therapies as well as the identification of resistance mechanisms to guide targeted therapy. Although the field of ctDNA studies offers a wide range of applications, including in early disease, in this review we mainly focus on the role of ctDNA in the dynamic molecular characterization of unresectable locally advanced and metastatic BC (mBC). Here, we provide clinical practice guidance for the rapidly evolving field of molecular profiling of mBC, outlining the current landscape of liquid biopsy applications and how to choose the right ctDNA assay. Additionally, we underline the importance of exploring the clinical relevance of novel molecular alterations that potentially represent therapeutic targets in mBC, along with mutations where targeted therapy is already approved. Finally, we present a potential roadmap for integrating ctDNA analysis into clinical practice.

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Measurement of Circulating Cell-Free DNA Levels by a Simple Fluorescent Test in Patients With Breast Cancer

Abstract: CFD measured using a simple fluorometric assay has shown good correlation to stage and enhanced sensitivity to locally advanced disease. A large prospective study is warranted to evaluate if inclusion of this method as a decisive marker before mammography is advantageous.

Cited by 58 publications

References 20 publications

Circulating Cell-Free DNA Levels in Patients with Metastatic Renal Cell Carcinoma

Circulating Cell-Free DNA Levels in Patients with Metastatic Renal Cell Carcinoma

Analysis of circulating tumor DNA in breast cancer as a diagnostic and prognostic biomarker

Clinical applications of next‐generation sequencing‐based ctDNA analyses in breast cancer: defining treatment targets and dynamic changes during disease progression

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