The Relationship Between Transcriptional Mediator Subunit 1 And Endocrine Therapy Sensitivity Of Breast Cancer

Objective: Breast cancer is one of the most common tumors in women.Endocrine therapy is one of the main treatments for hormone receptor-positive breast cancer,which significantly improved the prognosis of the patients.One third of hormone receptor positive breast cancer patients are resistant to primary endocrine therapy.Some patients developed resistance to endocrine therapy after a period of treatment.To study the mechanism of endocrine therapy resistance and explore new factor to predict the sensitivity of endocrine therapy could improve the survival of breast cancer.This study intends to explore the correlation of clinicopathological parameters and the sensitivity of endocrine therapy,and further explore possible mechanisms.Methods: We collected breast cancer patients who had received endocrine therapy in our hospital from 2004 to 2015,and analyzed the relationship between clinical and pathological parameters and the sensitivity to endocrine therapy.The patients were followed up.The sensitivity of endocrine therapy was determined according to the CSCO guidelines.The relationship between the clinicopathological parameters and the endocrine therapy sensitivity was analyzed to find the predictor for the sensitivity of endocrine therapy.Bc-GenEx Miner v4.4,TCGA database and KM-plotter and other public databases were used to further explore possible mechanisms.Results: 121 patients who had received endocrine therapy in our hospital were enrolled.The results showed that age,T stage,ER and PR expression status were not related to the sensitivity of patients to endocrine therapy.The patients with higher N stage were more likely to develop drug resistance(?2 = 10.897,P = 0.001),the patients with higher TNM stage were more likely to develop drug resistance(?2 = 6.487,P = 0.039),HER-2protein positive patients were more likely to develop drug resistance to endocrine therapy than HER-2 protein negative patients(?2 = 4.650,P = 0.031).We used bc-GenEx Miner v4.4 for gene correlation analysis to explore factors related to HER-2 expression,and the results showed that MED1 mRNA expression was significantly positively correlated with HER-2 m RNA expression(r = 0.52,P <0.0001).Further analysis of the TCGA database showed that the high expression rate of MED1 mRNA in the HER-2 protein positive group was significantly higher than that in the HER-2 protein negative group(?2 =177.180,P = 0.000).Further KM-plotter survival analysis showed that high MED1 expression group showed significantly worse DFS than low MED1 expression group[HR = 1.46(1.12-1.9),P = 0.0046 ] in endocrine therapy treated ER+ patients,suggesting that patients with high expression of MED1 had low sensitivity to endocrine therapy.Conclusion: Patients with HER-2 protein-positive breast cancer were relative resistant to endocrine therapy.MED1 might be a factor that mediates HER-2 protein induced endocrine resistance.