Identification and Functional Verification of Drug-Resistant Gene Mutations Associated with Breast Cancer Brain Metastasis Based on Cerebrospinal Fluid and Blood Samples
[Objective]This study aims to investigate the gene mutation profile in cerebrospinal fluid(CSF)/blood-derived samples from patients with brain metastases of breast cancer for screening drug-resistant genes to verify their resistance mechanisms.[Methods]A total of 70 patients with brain metastases from breast cancer trea-ted in our hospital were selected for the study.Second-generation sequencing technology was used to detect circu-lating tumor DNA(ctDNA)in CSF and blood samples to understand the gene mutation status,and to screen drug resistance and analyze the association with mutant genes.[Results]The main gene mutations detected in the 70 pa-tients included TP53,HER2,PIK3 CA,BRCA1,and BRCA2.The mutation detection rate in CSF-derived sam-ples was 100%(70/70),which was higher than 65.71%(46/70)in blood-derived samples(P<0.05).Compared to 21 samples without HER2 and PIK3 CA mutations(considering as the control group),patients with HER2 mu-tations showed higher resistance to trastuzumab(P<0.05).Patients with PIK3 CA mutations did not show sta-tistically significant differences in resistance to trastuzumab,atezolizumab,paclitaxel,and doxorubicin,if com-pared to the control group(P<0.05).Similarly,the resistance of HER2 mutation patients to atezolizumab,pa-clitaxel,and doxorubicin was not significantly different from that of the control group(P<0.05).[Conclusion]CSF in patients with breast cancer brain metastases can more accurately reflect possible brain metastasis status in comparison to the blood.The detection of HER2 mutations suggests the presence of corresponding drug resist-ance,which is of significant importance for medication guidance and monitoring of drug resistance.
Breast Neoplasms/GENeoplasm MetastasisGenesDrug Tolerance
万方数据
维普
