The Connection Between ESR1 Mutations And Breast Cancer Endocrine Therapy Resistance

Objective:To compare the efficacy of exemestane and fulvestrant(500mg)for treatment of ESR1 mutated breast cancer patients,and the connection between ESR1 mutations and aromatase inhibitor acquired resistance.Methods:The study included patients from a randomized,open,multicenter clinical trial to evaluate the efficacy and safety of fulvestrant(500mg)versus exemestane for the treatment of postmenopausal estrogen receptor positive,HER2 negative advanced breast cancer patients after first-line non-steroid aromatase inhibitor adjuvant therapy,Cancer Hospital,Chinese Academy of Medical Sciences,2016.We collected blood sample from these patients,and detected ESR1 mutations through next generation sequence;at the same time,we evaluated efficacy of these patients according to RECIST 1.1,and furthermore,analyzed the connection between ESR1 mutations and efficacy.Results:1.Efficacy evaluation:We evaluated the treatment efficacy of 12 patients included in this study.They are divided into two groups——fives cases in exemestane group(control group)and seven cases in fulvestrant(500mg)group(experimental group)——and the fulvestrant(500mg)group was proved to had a better outcome.The indicators are compared below:exemestane VS fulvestrant(500mg):average PFS 2.8m VS 4.0m,ORR 0 VS 28.6%,DCR 20%VS 71.4%,TTF 2.9m VS 2.8m.2.Both groups of exemestane and fulvestrant(500mg)tolerated well with no report of adverse events.3.The connection between ESR1 mutations and efficacy:we found 3 different ESR1 mutations in the study,among which the efficacy of D538G treated with fulvestrant(500mg)was evaluated as SD,while other two ESR1 muations(E380Q and D530G,treated with exemestane and fulvestrant respectively)got PD.4.The change of mutation abundance after treatment:4 patients had a higher mutation abundance after treatment,with 3 patients PD and 1 SD;1 patients had a lower mutation abundance after treatment,with a SD outcome;however,the phenomenon of some mutations got higher abundance while the others got lower at the same time appeared in one patient.Conclusions:1.The results above showed a better efficacy of fulvestrant(500mg)group than exemestane.2.Both of the medicines are well tolerated.3.The connection between ESR1 mutations and endocrine resistance is not definite enough yet according to this study.4.During the treatment,the abundance of virulence mutations becoming higher might indicate a worse outcome,and so in the reverse.