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Old 02-10-2020, 12:33 PM   #1
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Join Date: Nov 2005
Posts: 410
Personalized Detection of Circulating Tumor DNAAntedates Breast Cancer Metastatic Rec

I might have posted this already.


AbstractPurpose:Up to 30% of patients with breast cancer relapseafter primary treatment. There are no sensitive and reliabletests to monitor these patients and detect distant metastasesbefore overt recurrence. Here, we demonstrate the use ofpersonalized circulating tumor DNA (ctDNA) profiling fordetection of recurrence in breast cancer.

Experimental Design:Forty-nine primary patients withbreast cancer were recruited following surgery and adjuvanttherapy. Plasma samples (n208) were collected every6 months for up to 4 years. Personalized assays targeting16 variants selected from primary tumor whole-exome datawere tested in serial plasma for the presence of ctDNA byultradeep sequencing (average>100,000X).Results:Plasma ctDNA was detected ahead of clinicalor radiologic relapse in 16 of the 18 relapsed patients(sensitivity of 89%); metastatic relapse was predicted witha lead time of up to 2 years (median, 8.9 months; range,0.524.0 months). None of the 31 nonrelapsing patientswere ctDNA-positive at any time point across 156 plasmasamples (specificity of 100%). Of the two relapsed patientswho were not detected in the study, thefirst had only a localrecurrence, whereas the second patient had bone recurrenceand had completed chemotherapy just 13 days prior toblood sampling.

Conclusions:This study demonstrates that patient-specific ctDNA analysis can be a sensitive and specificapproach for disease surveillance for patients withbreast cancer. More importantly, earlier detection of upto 2 years provides a possible window for therapeuticintervention
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