Introduction: 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 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.