Diagnostic Value of Concentration of Circulating Cell-Free DNA in Breast Cancer: A Meta-Analysis

Yu, Dandan; Tong, Yan; Guo, Xinnian; Feng, Lingfang; Jiang, Zhaoqiang; Ying, Shibo; Jia, Jinhua; Fang, Yuan; Yu, Min; Xia, Hailing; Shi, Li

doi:10.3389/fonc.2019.00095

Cited by 39 publications

(29 citation statements)

References 35 publications

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“…[56][57][58] cfDNA, as a liquid-based diagnostic tool, possessed equal sensitivity and specificity of 87% for breast cancer. 59 A meta-analysis further indicated that the plasma might be a good source of cfDNA for detection of breast cancer. 59 In a patient with HER2-positive BCBM, Siravegna et al 60 reported that cfDNA was more informative and sensitive than radiologic imaging.…”

Section: Discussionmentioning

confidence: 99%

Diagnostic Clinical Trials in Breast Cancer Brain Metastases: Barriers and Innovations

Fares

Kanojia

Rashidi

et al. 2019

Clinical Breast Cancer

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Optimal treatment of breast cancer brain metastases (BCBM) is often hampered by limitations in diagnostic abilities. Developing innovative tools for BCBM diagnosis is vital for early detection and effective treatment. In this study we explored the advances in trial for the diagnosis of BCBM, with review of the literature. On May 8, 2019, we searched ClinicalTrials.gov for interventional and diagnostic clinical trials involving BCBM, without limiting for date or location. Information on trial characteristics, experimental interventions, results, and publications were collected and analyzed. In addition, a systematic review of the literature was conducted to explore published studies related to BCBM diagnosis. Only 9 diagnostic trials explored BCBM. Of these, 1 trial was withdrawn because of low accrual numbers. Three trials were completed; however, none had published results. Modalities in trial for BCBM diagnosis entailed magnetic resonance imaging (MRI), computed tomography (CT), positron emission tomography (PET), PET-CT, nanobodies, and circulating tumor cells (CTCs), along with a collection of novel tracers and imaging biomarkers. MRI continues to be the diagnostic modality of choice, whereas CT is best suited for acute settings. Advances in PET and PET-CT allow the collection of metabolic and functional information related to BCBM. CTC characterization can help reflect on the molecular foundations of BCBM, whereas cell-free DNA offers new genetic material for further exploration in trials. The integration of machine learning in BCBM diagnosis seems inevitable as we continue to aim for rapid and accurate detection and better patient outcomes.

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Section: Discussionmentioning

confidence: 99%

Diagnostic Clinical Trials in Breast Cancer Brain Metastases: Barriers and Innovations

Fares

Kanojia

Rashidi

et al. 2019

Clinical Breast Cancer

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“…There are several important consequences of "oncogenic drivers" in benign conditions. First, there are the implications for early detection of cancer based on sensitive blood tests that assess circulating cell-free DNA (cfDNA) [130][131][132]. If mutations identical to those found in cancer also occur in conditions with no malignant predisposition, their presence may confound the early diagnosis of cancer premise that is the basis of these blood-based screening tests, such as the multicancer detection blood test developed by GRAIL that has been granted breakthrough status by the US Food and Drug Administration [133].…”

Section: Adrenocortical Cancersmentioning

confidence: 99%

The paradox of cancer genes in non-malignant conditions: implications for precision medicine

et al. 2020

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Next-generation sequencing has enabled patient selection for targeted drugs, some of which have shown remarkable efficacy in cancers that have the cognate molecular signatures. Intriguingly, rapidly emerging data indicate that altered genes representing oncogenic drivers can also be found in sporadic non-malignant conditions, some of which have negligible and/or low potential for transformation to cancer. For instance, activating KRAS mutations are discerned in endometriosis and in brain arteriovenous malformations, inactivating TP53 tumor suppressor mutations in rheumatoid arthritis synovium, and AKT, MAPK, and AMPK pathway gene alterations in the brains of Alzheimer's disease patients. Furthermore, these types of alterations may also characterize hereditary conditions that result in diverse disabilities and that are associated with a range of lifetime susceptibility to the development of cancer, varying from near universal to no elevated risk. Very recently, the repurposing of targeted cancer drugs for non-malignant conditions that are associated with these genomic alterations has yielded therapeutic successes. For instance, the phenotypic manifestations of CLOVES syndrome, which is characterized by tissue overgrowth and complex vascular anomalies that result from the activation of PIK3CA mutations, can be ameliorated by the PIK3CA inhibitor alpelisib, which was developed and approved for breast cancer. In this review, we discuss the profound implications of finding molecular alterations in non-malignant conditions that are indistinguishable from those driving cancers, with respect to our understanding of the genomic basis of medicine, the potential confounding effects in early cancer detection that relies on sensitive blood tests for oncogenic mutations, and the possibility of reverse repurposing drugs that are used in oncology in order to ameliorate nonmalignant illnesses and/or to prevent the emergence of cancer.

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“…However, since the tumor is a "moving target", with significant molecular alterations evolving during progression and in response to therapeutics, extending liquid biopsy to the genetic analysis of CTCs will further help to inform on these two relevant aspects of carcinogenesis and, consequently, to reduce mortality. In addition to CTCs, tumors can release DNA into the bloodstream, which is described as circulating tumor DNA (ctDNA) [13]. This cell-free DNA (cfDNA), although present also in healthy individuals, is significantly increased in cancer subjects [14].…”

Section: Introductionmentioning

confidence: 99%

“…Therefore, ctDNA is recognized as a novel biomarker in the diagnosis of several cancers, including gastric cancer, non-small lung cancer, and hepatocellular carcinoma [15][16][17]. In BC, the concentration of ctDNA has potential first diagnostic value for BC [13,18]. Given that the combination of as many parameters as possible may lead to achieve the maximum level of diagnostic and/or prognostic accuracy, in the present study, we carried out liquid biopsy through CTCs enumeration, ctcDNA and cftDNA quantification and sequencing, in early BC patients before and after surgery ( Figure 1), providing, for the first time to our knowledge, a complete picture, even though still limited to a small cohort of patients, of this potentially important diagnostic and prognostic strategy.…”

Section: Introductionmentioning

confidence: 99%

Liquid Biopsy in Early Breast Cancer: A Preliminary Report

Antognelli¹,

Rulli²,

Covarelli³

et al. 2020

ACO

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Background: Liquid biopsy (LB) is a technique that utilizes circulating biomarkers from cancer patients to provide information regarding the genetic landscape of the cancer. LB is emerging as an alternative and complementary diagnostic and prognostic tool to surgical biopsy and is expected to provide the tool for the implementation of precision oncology in clinical settings. In fact, it may contribute to enhance understanding of tumor heterogeneity and permitting the dynamic monitoring of treatment responses and genomic variations. Thus, LB is a promising method for the management of cancer, including breast cancer (BC), whose incidence in Italy is progressively increasing. Previous studies focused mainly on patients with advanced-stage BC. In the present study we evaluated the number of circulating tumor cells (CTCs), the quantity of cell free tumor DNA (cftDNA) and the analysis of the mutational profile of DNA from CTCs (ctcDNA) and cftDNA in early stage BC patients. Methods: Matched pre- and post-surgery blood samples were collected from 47 early stage BC patients. CTCs enumeration was done using Isoflux system, molecular profile of ctcDNA and cftDNA was performed with the Spotlight 59 Panels kit on a MiSeq Illumina instrument. Results: Eighty percent of samples was CTCs-positive, while healthy controls were all CTCs-negative. Forty-four patients provided a pre-surgery and 21 post-surgery sample. By comparing the number of CTCs post-surgery with that of pre-surgery, we found that 66% of patients showed a decreased number of CTCs, 14% of patients continued to have the same number of CTCs, while, interestingly, 19% of patients showed an increased number of CTCs. Next Generation Sequencing (NGS) of ctcDNA and cftDNA showed that 52% of samples had mutations in 9 genes (TP53, CDKN2A, FBXW7, PTPN11, KRAS, NRAS, BRAF, IDH1, ALK) and in 5 genes (PIK3CA, APC ALK, KRAS, TSC1), respectively, with KRAS and ALK overlapping and TP53 being the most frequently mutated gene in ctcDNA analysis. Conclusions: LB could facilitate early detection of minimal residual disease, aiding in the initiation of adjuvant therapy to prevent recurrence and progression towards metastasis, enhance individualized treatment and longitudinal screening, thus improving the clinical management and outcome of patients with early BC.

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Diagnostic Value of Concentration of Circulating Cell-Free DNA in Breast Cancer: A Meta-Analysis

Cited by 39 publications

References 35 publications

Diagnostic Clinical Trials in Breast Cancer Brain Metastases: Barriers and Innovations

Diagnostic Clinical Trials in Breast Cancer Brain Metastases: Barriers and Innovations

The paradox of cancer genes in non-malignant conditions: implications for precision medicine

Liquid Biopsy in Early Breast Cancer: A Preliminary Report

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