title: Cardiac glycosides and breast cancer risk: A systematic review and meta-analysis of observational studies.
abstract: Cardiac glycosides are phytoestrogens and have been linked to the risk of estrogen sensitive cancers such as uterus cancer. However, the association between use of cardiac glycosides and risk of breast cancer remains unclear. We investigated the association between cardiac glycosides use and the risk of breast cancer by systematically reviewing the published literature and performing meta-analyses. A comprehensive literature search was performed using MEDLINE, EMBASE, Web of Science and SCOPUS to identify all relevant articles published up to November 2015. Risk estimates, and accompanying standard errors, for the association between cardiac glycoside use and breast cancer were extracted from identified studies. Meta-analysis models were used to calculate a combined hazard ratio (HR), and 95% confidence interval (CI), and to investigate heterogeneity between studies. In total, nine studies were identified investigating cardiac glycosides use and risk of developing breast cancer. Overall, there was evidence to suggest an association between cardiac glycosides use and breast cancer risk (HR = 1.34; 95% CI 1.25, 1.44; p < 0.001) with little variation in the association between studies (I2= 16%, p for heterogeneity = 0.30). Results were little altered when analysis was restricted to studies with high quality scores or cohort studies. Overall, there was a 34% increase in breast risk with use of cardiac glycosides but it is unclear whether this association reflects confounding or is causal. Further observational studies are required to examine this association particularly for estrogen receptor positive breast cancer and to explore the role of potential confounding variables.
authors.affiliation: Cancer Epidemiology and Health Services Research Group, Centre for Public Health, Queen's University Belfast, Belfast, Northern Ireland.
authors.forename: Reema A
authors.initials: RA
authors.lastname: Karasneh
authors.affiliation: Cancer Epidemiology and Health Services Research Group, Centre for Public Health, Queen's University Belfast, Belfast, Northern Ireland.|Centre of Excellence for Public Health (NI), Centre for Public Health, Queen's University Belfast, Belfast, Northern Ireland.
authors.forename: Liam J
authors.initials: LJ
authors.lastname: Murray
authors.affiliation: Cancer Epidemiology and Health Services Research Group, Centre for Public Health, Queen's University Belfast, Belfast, Northern Ireland.
authors.forename: Chris R
authors.initials: CR
authors.lastname: Cardwell
mesh_terms: D001943:Breast Neoplasms / Q000139:chemically induced* / Q000453:epidemiology; D002301:Cardiac Glycosides / Q000009:adverse effects*; D015984:Causality; D015331:Cohort Studies; D016001:Confidence Intervals; D015986:Confounding Factors, Epidemiologic; D004967:Estrogens; D005260:Female; D006801:Humans; D015994:Incidence; D008954:Models, Biological; D009376:Neoplasms, Hormone-Dependent / Q000139:chemically induced* / Q000453:epidemiology; D064887:Observational Studies as Topic; D048789:Phytoestrogens / Q000009:adverse effects*; D012042:Registries; D012307:Risk Factors; D011795:Surveys and Questionnaires
chemical_list: D002301:Cardiac Glycosides; D004967:Estrogens; D048789:Phytoestrogens
keywords: breast cancer; cardiac glycosides; epidemiology; meta-analysis