title: Hypomethylation of DNA-binding inhibitor 4 serves as a potential biomarker in distinguishing acquired tamoxifen-refractory breast cancer.
abstract: OBJECTIVE
  To explore the methylation status of DNA-binding inhibitor 4 (ID4) in tamoxifen-refractory (TR) breast cancer.
  
  
  METHODS
  From January 2012 to December 2014, breast cancer patients managed by radical mastectomy previously and receiving tamoxifen treatment for at least 12 months were enrolled. According to the response to tamoxifen, patients were divided into TR group and tamoxifen-sensitive (TS) group. Genomic DNA was isolated from fasting venous blood, and methylight technique was applied to determine the methylation status of ID4.
  
  
  RESULTS
  43 patients with TS breast cancer and 31 patients with TR breast cancer were enrolled. No significant difference between groups was observed in term of patients' characteristics, such as age (P=0.693), progesterone receptor (P=0.970), menopausal status (P=0.784) and histological type (P=0.537), while the stage of cancer in TR group was significantly higher than TS group (P<0.001). Compared to TS group, PMR of ID4 was significantly higher in TR group (P=0.002). ROC curve analysis indicated that ID4 yielded an AUC of 0.716 with 77.4% sensitivity and 62.79% specificity in distinguishing TR breast cancer at the cut point of 3.8%. The PMR cut point of ID4 was set at 6.8% in survival analysis, log-rank test indicated the risk of disease progression was comparable between patients with ID4 hypermethylation or hypomethylation (P=0.287).
  
  
  CONCLUSIONS
  ID4 hypomethylation is present in TR breast cancer, and it may serve as a potential biomarker in distinguishing TR breast cancer. However, the results need further validation in larger studies.
authors.affiliation: Tianjin Medical University Cancer Institute and Hospital, National Clinical Research Center for Cancer Tianjin, China ; Key Laboratory of Cancer Prevention and Therapy Tianjin, China ; Key Laboratory of Breast Cancer Prevention and Therapy, Tianjin Medical University, Ministry of Education Tianjin 300060, China ; Department of Oncologic Surgery, Weinan Center Hospital Weinan 714000, Shaanxi, China.
authors.forename: Yonghui
authors.initials: Y
authors.lastname: Zhang
authors.affiliation: Tianjin Medical University Cancer Institute and Hospital, National Clinical Research Center for Cancer Tianjin, China ; Key Laboratory of Cancer Prevention and Therapy Tianjin, China ; Key Laboratory of Breast Cancer Prevention and Therapy, Tianjin Medical University, Ministry of Education Tianjin 300060, China.
authors.forename: Bin
authors.initials: B
authors.lastname: Zhang
authors.affiliation: Tianjin Medical University Cancer Institute and Hospital, National Clinical Research Center for Cancer Tianjin, China ; Key Laboratory of Cancer Prevention and Therapy Tianjin, China ; Key Laboratory of Breast Cancer Prevention and Therapy, Tianjin Medical University, Ministry of Education Tianjin 300060, China.
authors.forename: Jing
authors.initials: J
authors.lastname: Fang
authors.affiliation: Tianjin Medical University Cancer Institute and Hospital, National Clinical Research Center for Cancer Tianjin, China ; Key Laboratory of Cancer Prevention and Therapy Tianjin, China ; Key Laboratory of Breast Cancer Prevention and Therapy, Tianjin Medical University, Ministry of Education Tianjin 300060, China.
authors.forename: Xuchen
authors.initials: X
authors.lastname: Cao
mesh_terms: D000328:Adult; D018931:Antineoplastic Agents, Hormonal / Q000627:therapeutic use*; D001940:Breast / Q000473:pathology; D001943:Breast Neoplasms / Q000175:diagnosis* / Q000188:drug therapy / Q000235:genetics* / Q000473:pathology; D019175:DNA Methylation; D003937:Diagnosis, Differential; D005260:Female; D006801:Humans; D051796:Inhibitor of Differentiation Proteins / Q000235:genetics*; D008875:Middle Aged; D013629:Tamoxifen / Q000627:therapeutic use*
chemical_list: D018931:Antineoplastic Agents, Hormonal; C490128:ID4 protein, human; D051796:Inhibitor of Differentiation Proteins; D013629:Tamoxifen
keywords: DNA-binding inhibitor 4; breast cancer; mastectomy; methylight; survival analysis; tamoxifen