title: Digitalis Use and the Risk of Breast Cancer: A Systematic Review and Meta-Analysis.
abstract: Previous epidemiological studies have indicated an increased risk of breast cancer associated with digitalis medication, though results are inconsistent. We performed this systematic review of available epidemiological studies to clarify the association between digitalis use and the risk of breast cancer.
  
  
  
  A search of studies published through May 2016 in MEDLINE and EMBASE databases was performed, supplemented by manual searches of reference lists. The quality of the included studies was assessed, and relative risks were pooled using both random- and fixed-effect models.
  
  
  
  Three case-control studies and six cohort studies were identified. Meta-analysis generated a pooled relative risk of 1.35 (95% confidence interval 1.24-1.46) in both fixed- and random-effect models. The heterogeneity test suggested low heterogeneity across studies. The funnel plot suggested no existence of publication bias. Subgroup analysis by study design revealed an increased risk of breast cancer associated with digitalis use from cohort studies only (relative risk = 1.39, 95% confidence interval 1.27-1.52), rather than from case-control studies. Studies with adjustment for tobacco smoking or body mass index generated lower overall estimates than those not adjusted.
  
  
  
  Existing epidemiological evidence regarding the association between digitalis use and the risk of breast cancer remains inconclusive and more well-designed studies are still needed.
authors.affiliation: Department of Hepatobiliary Surgery, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China.
authors.forename: Chen
authors.initials: C
authors.lastname: Zhang
authors.affiliation: Department of Molecular Medicine and Surgery, Karolinska Institutet, Karolinska University Hospital, Stockholm, Sweden.
authors.forename: Shao-Hua
authors.initials: SH
authors.lastname: Xie
authors.affiliation: Cancer Center, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, 1277 Jiefang Avenue, Wuhan, 430022, China.
authors.forename: Bingfei
authors.initials: B
authors.lastname: Xu
authors.affiliation: Department of Obsterics and Gynecology, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China.
authors.forename: Shi
authors.initials: S
authors.lastname: Lu
authors.affiliation: Cancer Center, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, 1277 Jiefang Avenue, Wuhan, 430022, China. liupian@hust.edu.cn.
authors.forename: Pian
authors.initials: P
authors.lastname: Liu
mesh_terms: D015992:Body Mass Index; D001943:Breast Neoplasms / Q000453:epidemiology / Q000209:etiology*; D002316:Cardiotonic Agents / Q000008:administration & dosage / Q000009:adverse effects*; D004071:Digitalis Glycosides / Q000008:administration & dosage / Q000009:adverse effects*; D005260:Female; D006801:Humans; D015233:Models, Statistical; D012107:Research Design; D012307:Risk Factors; D012907:Smoking / Q000453:epidemiology
chemical_list: D002316:Cardiotonic Agents; D004071:Digitalis Glycosides