The Potential Feasibility Of High-throughput Sequencing Technique In Detection Of Breast Cancer

Background: Breast cancer is the commonest female cancer of the world.In recent years,lots of efforts have been made to reduce the mortality of breast cancer.And it is well established that early detection of breast cancer might be the most effective way to achieve better prognosis.However,mammography and ultrasound screening can’t provide clarification of lesions without tissue biopsy,which is an invasive method to define the diagnosis.Must be noted that,numerous of impalpable lesions were missed diagnosis,which further led to worse prognosis.ctDNA(Circulating tumor DNA)defined by short DNA fragments released by necrosis or apoptosis of tumor cells from different sites,and it can be directly secreted by tumor cells as well.Originating from tumor cells,ctDNA may carry the same mutations as those tumor tissue.As generated by multiple tumor sites,it has potential to overcome heterogeneity of tumor.Due to its great promising clinical applications,ctDNA serving as a liquid biopsy becomes a hot research topic.It is reported that measurement of ctDNA can detect recurrence 7.9 months earlier than clinical methods.However,the concentration of ctDNA in plasma of early stage breast cancer patients is extremely low,which brings challenges to detect ctDNA in such group of patients.Next generation sequencing has enhanced the sensitivity and specificity,allowing the detection of rare sequences.This study used high-throughput sequencing technique,which has advantages of ultra-high sensitivity and sequencing depth,able to detect ctDNA at extremely low concentration.This study aims to provide insights into the potential feasibility of high-throughput sequencing technique in detection of breast cancer.Method: We have collected patients’ peripheral blood before surgery.For breast cancer patients,samples of their tumor tissue were also collected.All samples were examined cancerrelated genes by using high-throughput sequencing technique.Sensitivity and specificity,as well as concordance between plasma ctDNA and tumor tissue DNA were reported.Result: 27 patients(6 benign and 21 malignant)were included.1 out of 6 patients with benign lesion were detected mutations,while 16 out of 21 breast cancer were found mutations.Overall sensitivity is 76.19%,and overall specificity is 83.33%.The concordance between plasma ctDNA and tumor tissue DNA were 23.81%.The most commonly mutated genes of tumor tissue DNA are previously reported breast cancer related genes of TP53、PIK3CA、PTEN,while of ctDNA are TP53、ATM、BRCA2.Conclusion: In this study,we showed the potential of plasma ctDNA sequencing for gene mutation detection in breast cancer.Although with limited number of samples,the data encourage further improvement of the gene panel and the validation of ctDNA assay as a noninvasive approach to the cancer screening.