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Breast Cancer Research

, 15:R13

First Online: 19 February 2013Received: 28 June 2012Revised: 09 January 2013Accepted: 08 February 2013DOI: 10.1186-bcr3386

Cite this article as: Biggar, R.J., Andersen, E.W., Kroman, N. et al. Breast Cancer Res 2013 15: R13. doi:10.1186-bcr3386


IntroductionDigoxin 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.

MethodsIncident 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.

ResultsAt 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.

ConclusionsBreast 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.

AbbreviationsAIaromatase inhibitor

ATCanatomical therapeutic chemicals

ERestrogen receptor

HRhazard ratio

LOESSlocally weighted scatterplot smoothing


nnumber of observations.

Electronic supplementary materialThe online version of this article doi:10.1186-bcr3386 contains supplementary material, which is available to authorized users.

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Autor: Robert J Biggar - Elisabeth W Andersen - Niels Kroman - Jan Wohlfahrt - Mads Melbye


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