Circulating Tumor DNA Is Effective for the Detection of EGFR Mutation in Non–Small Cell Lung Cancer: A Meta-analysis

Qiu, Mantang; Wang, Jie; Xu, Youtao; Ding, Xiangxiang; Li, Ming; Jiang, Feng; Xu, Lin; Yin, Rong

doi:10.1158/1055-9965.epi-14-0895

Cited by 166 publications

(127 citation statements)

References 56 publications

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“…IC: 0.51-0.72) and specificity of 0.96 (95% IC: 0.93-0.98) are consistent with our results. 19 In contrast, Dawson et al reported mutation detection in 18 of the 19 women and in 80 of the 97 plasma samples (82%) analyzed; however, these researchers used larger blood samples (30 ml each vs. 0.4-2 ml in our study). 17 The use of dPCR for ctDNA analysis has been reported previously for MBC, but only after deep sequencing of the primary tumor to define the non-recurrent driver mutations of TP53, PI3KCA or PTEN.…”

Section: Short Reportcontrasting

confidence: 62%

Short report: Monitoring ESR1 mutations by circulating tumor DNA in aromatase inhibitor resistant metastatic breast cancer

Sefrioui

Perdrix

Sarafan-Vasseur

et al. 2015

Intl Journal of Cancer

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Acquired estrogen receptor gene (ESR1) mutations have been recently reported as a marker of resistance to aromatase inhibitors in hormone receptor positive metastatic breast cancer. We retrospectively considered seven patients treated for metastatic breast cancer with available samples from the primary tumor before any treatment, cryopreserved metastasis removed during progression and concomitant plasmas. All these seven patients were in disease progression after previous exposure to aromatase inhibitors for at least 6 months, and were assessed for ESR1 mutations detection in tumor and circulating DNA. For these patients, Sanger sequencing identified four metastases with clear ESR1 mutation and one possible, whereas digital PCR identified six mutated metastases. Then, under blind conditions and using digital PCR, corresponding circulating ESR1 mutations were successfully detected in four of these six metastatic breast cancer patients. Moreover, in two patients with serial blood samples following treatments exposure, the monitoring of circulating ESR1 mutations clearly predicted disease evolution. In the context of high interest for ESR1 mutations, our results highlight that these acquired recurrent mutations may be tracked in circulating tumor DNA and may be of clinical relevance for metastatic breast cancer patient monitoring.Nearly 70% of breast cancers are hormone receptor positive (HR1) and potentially sensitive to hormonal therapy. Aromatase inhibitors (AI) or tamoxifen is the recommended first line hormonal therapy in postmenopausal HR1 metastatic breast cancer (MBC).1,2 Nevertheless, disease progression is usually observed within a few months after treatment initiation.3,4 Acquired resistance to hormonal therapy may be based on activating mutations in the estrogen receptor gene (ESR1). These mutations have been detected in HR1 MBC patients previously exposed to hormonal therapy, including treatment with an AI in all cases. The frequencies of ESR1 mutations was 25% (nine of 36), 38% (five of 13) and 54% (six of 11) among these cohorts. [5][6][7] Approximately 12 ESR1 point mutations have been described, with a hot spot confined to codons 537 and 538 in exon 8. 8 These mutations result in a ligand-independent estrogen receptor (ER) activity. In vitro and preclinical data suggest that ESR1 mutations lead to complete AI resistance and to partial resistance to ER agonists and antagonists.9,10 The detection of ESR1-activating mutations may be relevant for guiding clinicians between endocrine and nonendocrine therapy.11 Thus far, ESR1 genotyping must be performed on metastases: this method is hardly compatible with repetitive sampling analyses for disease monitoring. Circulating tumor DNA (ctDNA) analysis is considered a promising tool for providing relevant prognostic and/or predictive information instead of tumor sampling. 12,13

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Section: Short Reportcontrasting

confidence: 62%

Short report: Monitoring ESR1 mutations by circulating tumor DNA in aromatase inhibitor resistant metastatic breast cancer

Sefrioui

Perdrix

Sarafan-Vasseur

et al. 2015

Intl Journal of Cancer

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“…Another meta-analysis of 25 studies demonstrated the pooled overall sensitivity, specificity, and concordance rate of ctDNA compared to tissue as 61%, 90% and 79%, respectively (30). Qiu et al showed a pooled sensitivity and specificity of 62% and 95.9% for ctDNA to detect EGFR mutations in their meta-analysis of 27 studies involving 3,110 participants (31). The large multicenter non-interventional ASSESS study investigated the utility of ctDNA EGFR testing in the real world setting in patients with metastatic NSCLC in Europe and Japan.…”

Section: Utilizing Ctdna In Initial Diagnosismentioning

confidence: 99%

Circulating DNA in EGFR-mutated lung cancer

Singh¹,

Li²,

Cheng³

2017

Ann. Transl. Med.

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Circulating tumor DNA (ctDNA) consists of short double stranded DNA fragments that are released by tumors including non-small cell lung cancer (NSCLC). With the identification of driver mutations in the epidermal growth factor receptor (EGFR) gene and development of targeted tyrosine kinase inhibitors (TKIs), the clinical outcome of NSCLC patients in this subgroup has improved tremendously.The gold standard to assess EGFR mutation is through tissue biopsy, which can be limited by difficulty in accessing the tumor, inability of patients to tolerate invasive procedures, insufficient sample for molecular testing and inability to capture intratumoral heterogeneity. The great need for rapid and accurate identification of activating EGFR mutations in NSCLC patients paves the road for ctDNA technology.Studies have demonstrated ctDNA to be a reliable complement to tumor genotyping. Platforms like digital polymerase chain reaction (PCR) and next-generation sequencing based analyses have made it possible to identify EGFR mutations in plasma with high sensitivity and specificity. This article will provide an overview on ctDNA in the context of EGFR mutated NSCLC, especially its emerging applications in diagnosis, disease surveillance, treatment monitoring and detection of resistance mechanisms.

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“…With regard to specific genetic alterations, one clear example is the clinical utility of the detection of EGFR mutations in the cfDNA of NSCLC patients treated with gefitinib (25) or erlotinib (26). EGFR mutations have also been shown to be of prognostic and predictive value, and patients with an activating mutation in EGFR in cfDNA have been reported to respond significantly better to TKIs (27). KRAS gene alterations detected in cfDNA have also been used as prognostic biomarkers, mainly in colorectal and pancreatic cancer (28,29).…”

Section: Circulating Free Dna (Cfdna) As Prognostic and Monitoring Tementioning

confidence: 99%

KRAS mutations in the circulating free DNA (cfDNA) of non-small cell lung cancer (NSCLC) patients

Garzón¹,

Villatoro²,

Teixidó³

et al. 2016

Transl. Lung Cancer Res.

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Circulating Tumor DNA Is Effective for the Detection of EGFR Mutation in Non–Small Cell Lung Cancer: A Meta-analysis

Cited by 166 publications

References 56 publications

Short report: Monitoring ESR1 mutations by circulating tumor DNA in aromatase inhibitor resistant metastatic breast cancer

Short report: Monitoring ESR1 mutations by circulating tumor DNA in aromatase inhibitor resistant metastatic breast cancer

Circulating DNA in EGFR-mutated lung cancer

KRAS mutations in the circulating free DNA (cfDNA) of non-small cell lung cancer (NSCLC) patients

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