title: Digoxin use and the risk of breast cancer in women.
abstract: OBJECTIVE
  Digoxin resembles estrogen chemically and may have estrogenic effect. We hypothesized that digoxin use might increase breast cancer incidence and examined if use might be associated with risk of breast cancer, categorized by estrogen receptor (ER) status. To determine if being under care for heart disease biased the findings, rate ratios in users of angina drugs were similarly evaluated as a control exposure group.
  
  
  METHODS
  Women using digoxin and angina drugs were identified in the nationwide Danish Prescription Database, available between 1995 and 2008. Incident breast cancers were identified in the Danish Cancer Registry and further classifying by ER status. Relative risks (RR) were compared to nonusers using age- and period-adjusted incidence rate ratios.
  
  
  RESULTS
  Two thousand one hundred forty-four of 104,648 women using digoxin developed breast cancer. Current digoxin users were at increased risk of breast cancer (RR, 1.39; 95% CI, 1.32 to 1.46), but risk was not increased in former users (RR, 0.91; 95% CI, 0.83 to 1.00). The increased risks in digoxin users were marginally higher for ER-positive breast cancers (RR, 1.35; 95% CI, 1.26 to 1.45) and ER unknown breast cancers (RR, 1.51; 95% CI, 1.38 to 1.64) than for ER-negative breast cancers (RR, 1.20; 95% CI, 1.03 to 1.40). Among 137,493 women exposed to angina drugs only (a comparison group with cardiovascular disease; n = 2,658 breast cancers), incidence was not increased in current or former users.
  
  
  CONCLUSIONS
  Women currently using digoxin had a significantly increased risk of breast cancer. Risk normalized when digoxin was stopped. No risk increases were observed in women using angina drugs only. The higher risk of developing ER-positive breast cancers supports an estrogen-mimicking mechanism.
authors.affiliation: Statens Serum Institut, Copenhagen, Denmark. rjbiggar@gmail.com
authors.forename: Robert J
authors.initials: RJ
authors.lastname: Biggar
authors.forename: Jan
authors.initials: J
authors.lastname: Wohlfahrt
authors.forename: Anna
authors.initials: A
authors.lastname: Oudin
authors.forename: Thomas
authors.initials: T
authors.lastname: Hjuler
authors.forename: Mads
authors.initials: M
authors.lastname: Melbye
mesh_terms: D000328:Adult; D017677:Age Distribution; D000368:Aged; D000369:Aged, 80 and over; D001943:Breast Neoplasms / Q000139:chemically induced* / Q000453:epidemiology*; D002316:Cardiotonic Agents / Q000009:adverse effects*; D004077:Digoxin / Q000009:adverse effects*; D005260:Female; D006801:Humans; D015994:Incidence; D008875:Middle Aged; D011960:Receptors, Estrogen / Q000096:biosynthesis; D012307:Risk Factors; D055815:Young Adult
chemical_list: D002316:Cardiotonic Agents; D011960:Receptors, Estrogen; D004077:Digoxin