Exploration Of Therapeutic Models And Response-related Factors Of Advanced Breast Cancer

Background and Objective:Exosomes,which are extracellular vesicles secreted by various cells,carries a large number of proteins,nucleic acids and other components related to donor cell.Recent studies have found that it is closely related to the invasion,metastasis and drug resistance of breast cancer.In this study,exploratory studies of plasma exosomal miRNAs were performed in patients with advanced breast cancer receiving first-line treatment with docetaxel plus capecitabine regimen in order to explore molecular markers that can predict chemotherapy sensitivity,efficacy,and prognosis.Methods:Eighteen advanced breast cancer patients treated with docetaxel and capecitabine as first line treatment betweent May 2014 to March 2016 were included in the analysis.Plasma exosomes microRNAs were compared in patients with different efficacy.The differences in expression levels of exosomes miRNAs and the analysis of downstream target genes and their functions and signal transduction pathways through bioinformatics methods to explore the relevance of the diagnosis of plasma exosomal miRNAs and breast cancer and the relation between exosome miRNA regulation network and chemotherapy efficacy of breast cancer.Results:Through the second-generation sequencing,1513 known miRNAs were obtained.miR-451a expressed the highest level in plasma exosomes of all patients.Based on the sensitivity of chemotherapy,before and after chemotherapy,differences in efficacy and molecular type,the differential expression of miRNAs was analyzed among different groups of samples.Eighteen,twenty-one,fifteen and eleven differentially expressed miRNAs were screened out.Among them,18 miRNAs such as miR-218-5p were showed significant correlation with overall survival in the Kaplan Meier Plotter database(p less than 0.05).Target gene prediction of differentially expressed miRNAs and clustering and pathway analysis revealed that the function of those target genes mainly involved in biological processes such as RNA transcription,cell proliferation,gene expression and drug reactions,and mainly involved in downstream signaling pathways include PI3K/AKt signaling pathways,cell adhesion,cell cycle,and Wnt signaling pathways.Conclusion:Exosome miR-451 may become a potential breast cancer-related tumor marker.Multiple miRNAs such as exosomes miR-1246,miR-30d,and miR-199b have been shown to correlate with chemotherapy efficacy and prognosis in advanced breast cancers in specific subgroups,and may be potential biomarkers for curative effect survey and prognosis prediction.Background and Objective:Currently,there are no standard regimens available for metastatic breast cancer patients who have failed>3 chemotherapy treatments.The aim of this study was to assess whether weekly low-dose bevacizumab-based regimens were well-tolerated and would improve efficacy in metastatic breast cancer patients(MBC)who had failed numerous therapies.Methods:Seventeen patients with MBC who were heavily pretreated with a median of five(range 1-10)regimens of therapy between 2012 and 2016 were included in the analysis.The bevacizumab was administered at a dose of 100 mg intravenously once a week combined with one or two types of chemotherapeutic drugs until a confirmed disease progression or an intolerable adverse event was observed.And another 10 MBC patients who received 15 mg/kg bevacizumab every 3 weeks at the same time period with low-dose group patients were also analyzed.Results:The median progression-free survival(PFS)in whole study group was 4.2 months(95%confidence interval,2.7-5.7 months),the objective response rate was 11.1%,and the clinical benefit rate was 33.3%.The median PFS of low-dose group was 3.4 months(95%confidence interval[CI],2.0 to 4.8 months).There was no significant difference of PFS between two groups.In low-dose group,there were three patients achieved partial response,while one had stable disease for>24 weeks,the objective response rate was significantly better in low-dose group(17.6%vs.0.0,p<0.001).Totally,the safety of whole population was tolerable,and no significant difference was observed between two groups.The most common adverse events were neutropenia(55.6%)and G1/2 gastrointestinal toxity(18.5%).The reported bevacizumab-related adverse events included bleeding and hypertension.The bleeding was mainly mild mucosal bleeding,weakly positive occult tests and prolonged menstrual periods,and clinical intervention was not required.Conclusion:Weekly low-dose bevacizumab combined with chemotherapy shows both a relative favorable clinical response and tolerable toxicity,which provides a feasible option for heavily pretreated MBC patients.