title: Breast cancer in women using digoxin: tumor characteristics and relapse risk.
abstract: BACKGROUND
  Digoxin use is associated with increased incidence of breast and uterus cancers. We postulated that digoxin use might affect tumor characteristics and increase relapse risk in women with breast cancer.
  
  
  METHODS
  Incident breast cancer cases in Danish women (n = 49,312; 1995 to 2008) were identified. Analyses were conducted in women 20 to 74 years old. Relapse hazard ratios (HR) were compared in women using and not using digoxin, adjusting for age, calendar period, protocol, tumor size, nodal involvement, histology grade, estrogen-receptor (ER) status, and anti-estrogen therapy in Cox regression models.
  
  
  RESULTS
  At diagnosis, tumors in digoxin users were more likely ER+ (85.4% vs. 78.6%: P = 0.002) and have grade 1 ductal histology (37.2% vs. 25.7%; P = 0.004), compared to non-users. 45 relapses occurred in women already using digoxin at breast cancer diagnosis (1,487 person-years); 24 relapses occurred in women later starting digoxin (384 person-years). Overall relapse risk HR in digoxin users was 1.13 (95% confidence interval: 0.88, 1.46) compared to non-users. Relapse risk in digoxin users was significantly increased in the first year (2.19; 1.26, 3.78) but not thereafter (0.99; 0.74, 1.32) (P = 0.02 for difference in HRs). First-year relapse hazard was high in digoxin-using women with ER+ tumors (2.51; 1.39, 4.55) but not ER- tumors (0.72; 0.10, 5.27). Recurrence hazard was not significantly changed among digoxin-using women also using tamoxifen.
  
  
  CONCLUSIONS
  Breast cancers arising in digoxin-using women had better prognostic features. After adjustment for markers, overall breast cancer relapse risk in digoxin users was not increased significantly, although recurrence hazards for ER+ tumors were higher in the first year following diagnosis.
authors: Robert J
authors: RJ
authors: Biggar
authors: Elisabeth W
authors: EW
authors: Andersen
authors: Niels
authors: N
authors: Kroman
authors: Jan
authors: J
authors: Wohlfahrt
authors: Mads
authors: M
authors: Melbye
mesh_terms: D000328:Adult; D000368:Aged; D047072:Aromatase Inhibitors / Q000008:administration & dosage / Q000009:adverse effects; D001943:Breast Neoplasms / Q000139:chemically induced / Q000188:drug therapy* / Q000453:epidemiology / Q000473:pathology*; D003718:Denmark; D004077:Digoxin / Q000008:administration & dosage / Q000009:adverse effects*; D005260:Female; D006331:Heart Diseases / Q000188:drug therapy / Q000473:pathology; D006801:Humans; D008875:Middle Aged; D009364:Neoplasm Recurrence, Local / Q000139:chemically induced / Q000453:epidemiology / Q000473:pathology*; D011379:Prognosis; D011960:Receptors, Estrogen / Q000378:metabolism*; D012307:Risk Factors; D013629:Tamoxifen / Q000008:administration & dosage / Q000009:adverse effects
chemical_list: D047072:Aromatase Inhibitors; D011960:Receptors, Estrogen; D013629:Tamoxifen; D004077:Digoxin