Circulating tumor DNA detection in primary breast cancer patients by targeted sequencing: Consistency with tumor DNA and factors influencing detection

Abstract

Background: Breast cancer is the most frequently diagnosed cancer worldwide in females with high mortality. As a noninvasive means to monitor the tumor genomes, circulating tumor DNA(ctDNA) detection has been applied to predict relapse and prognosis. However, systematic evaluation of ctDNA detection in plasma from patients with primary breast cancer(PBC) has not been performed. The aim of the study is to comprehensively assess the ctDNA detection and explore the factors affecting the release of ctDNA in patients with PBC. Methods: 71 females (8 stage I, 18 stage II, 38 stage III, 7 stage IV) with PBC newly diagnosed in Peking Union Medical College Hospital were selected in 2016. We analyzed genomic alterations of tumor tissues and matched plasma samples before the patients accepted any treatment by targeted sequencing in 1, 021 cancer-associated genes. Results: Of the 71 patients, 273 somatic mutations were detected in 71 tumor tissues, and 122 somatic mutations were detected in 49 plasmas; consistent mutations were observed in 44 patients. The concordance rate of plasma with tumor tissue was 61.97% and detection rate of it was 69.01%. 21 mutations including BRAF, GNAS, PTEN, were observed only in plasmas but not in tumor tissues. Consistent mutations were mainly TP53 and PIK3CA. The ctDNA detection rate was ly associated with tumor size (P=0.03) and lymph node metastasis or not(P=0.005), while it showed no significant differences with various age groups, HR status, Her2 amplification status, Ki67 levels and clinical pathological subtypes. Conclusions: The study provided evidence that ctDNA detection was a complementary approach for patients with PBC. It implied the PBC patients with larger tumor or lymph node metastasis were more likely to benefit from ctDNA detection.