Relationship Research between ctDNAGene Mutation Status and Effect of Fulvestrant for Hormone Receptor Positive Breast Cancer
Objective To investigate the relationship between mutation status of 9 genes in circulating tumor DNA (ctDNA) and effect of fulvestrant in treatment of hormone receptor (HR)positive breast cancer.Methods The paper included 61 patients with HR positive breast cancer with no hyperplasia of human epidermal growth factor receptor 2 (Her2) based on pathological diagnosis.Tumor tissue sequencing was carried out,and plasma samples before and 3 months after fulvestrant treatment were collected for ctDNA sequencing.Effective rate of fulvestrant treatment after 3 and 6 months was evaluated.Correlation between mutation status of 9 genes in ctDNA before treatment and effect after 3 months of treatment,as well as after 3 and 6 months of treatment was investigated with logistic regression analysis.Results Preliminary analysis revealed,mutation coincidence rates of ESR1,TP53,PIK3CA,ERBB2,MTOR,KRAS,RB1,AKT1,and TSC2 in tumor tissues and ctDNA were 88.2%,76.5%,84.2%,83.3%,71.4%,80.0%,62.5%,71.4%,and 80.0% respectively.Mutation rates in ESR1,TP53,PIK3CA,ERBB2,MTOR,KRAS,RB1,AKT1,and TSC2 were detected in ctDNA of 61 cases before treatment were 24.6%,21.3%,26.2%,16.4%,16.4%,19.7%,8.2%,8.2%,and 6.6% respectively.The response rates of patients with fulvestrant treatment after 3 months and 6 months were evaluated with the RECIST v1.1 standard,which were 19.7% and 23% respectively.Univariate logistic regression analysis found,mutations in 9 genes in ctDNA before treatment were not factors affecting effect after 3 months of treatment.The mutation of TSC2 in ctDNA at 3 months after treatment was closely related to effect of those after 6 months of treatment (P=0.039).Conclusion The mutation of TSC2 in ctDNA may be related to effect of fulvestrant of HR positive breast cancer,and more monitoring of treatment time points and verification of multi center cases is needed.