Abstract
// Yu Gui 1 , Xianchun Chen 1 , Shuman Xu 1 , Xiangdong Luo 2, 3 and Li Chen 1, 3 1 Breast Disease Center, Southwest Hospital, Third Military Medical University, Chongqing, China 2 Burn Research Institute, Southwest Hospital, Third Military Medical University, Chongqing, China 3 National Key Laboratory of Trauma and Burns, Chongqing Key Laboratory of Disease Proteomics, Chongqing, China Correspondence to: Li Chen, email: lichen2007@126.com Keywords: circulating tumor DNA; meta-analysis; breast cancer Received: August 23, 2017 Accepted: January 24, 2018 Epub: February 13, 2018 ABSTRACT Circulating tumor DNA (ctDNA) comprises single- or double-stranded DNA that likely originates from cancer cells. The prognostic value of ctDNA detection in breast cancer patients is currently under debate. Here, we conducted the first comprehensive meta-analysis of the published literature on the prognostic relevance of ctDNA, in patients with early- and advanced-stage disease.The PubMed and Embase databases were searched for studies on ctDNA in breast cancer patients.The main outcomes analyzed were overall survival (OS) and disease-free survival (DFS) in early-stage breast cancer patients as well as progression-free survival (PFS) and OS in metastatic breast cancer patients. Pooled hazard ratios (HRs) and 95% confidence intervals (CIs) were calculated using random and fixed-effects models. A total of 16 studies involving 2070 participants were identified as eligible for inclusion in our meta-analysis, and the results of the pooled analysis showed that the presence of ctDNA was significantly associated with poor OS (HR = 1.98; 95% CI: 1.38–2.83, P = 0.0002) and DFS/PFS (HR = 1.87; 95% CI: 1.35–2.60, P = 0.0002) in the total breast cancer population. Furthermore, subgroup analysis revealed that associations between the presence of ctDNA and the outcome endpoints (OS and PFS) were significant within the metastatic breast cancer patient group and in patients with TP53 or ESR1 mutations in ctDNA.The TP53 and ESR1 mutations in ctDNA are potential prognostic biomarkers and promising therapeutic targets for advanced breast cancer.
Highlights
Breast cancer is the most frequently diagnosed cancer worldwide and was the leading cause of cancer death in women in 2012 [1]
Subgroup analysis of the effect of gene mutations in Circulating tumor DNA (ctDNA) on breast cancer survival While evaluating the relevance of gene mutations, our results showed that patients with ESR1 and TP53 mutations in ctDNA were significantly associated with worse disease-free survival (DFS)/ progression-free survival (PFS) compared with control patients, with a pooled hazard ratios (HRs) of 1.79 and 2.20, respectively (Figure 4A)
Using the strict inclusion and exclusion criteria for patient selection, we identified 16 high-quality studies, and ctDNA assessment www.impactjournals.com/oncotarget was organized according to prognostic predictability regarding PFS/DFS and overall survival (OS) in breast cancer patients
Summary
Breast cancer is the most frequently diagnosed cancer worldwide and was the leading cause of cancer death in women in 2012 [1]. Breast cancer progression in patients is mainly monitored using serial physical examinations and radiographic imaging [3]. These strategies are largely effective for the detection of breast cancer progression when there are relatively significant changes. Non-invasive biomarkers that can guide personalized treatment, predict prognosis and facilitate reliable follow-up are needed. Potential noninvasive biomarkers, such as cancer antigen 15–3 and circulating tumor cells, have been studied in breast cancer patients. These markers have limited utility in clinical settings due to their low sensitivity and small range of dynamic change compared to the magnitude of change in tumor burden [7,8,9]
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