According to a study published early online in the Journal of Clinical Oncology, current use of digoxin may increase the risk of breast cancer, particularly those that are oestrogen-receptor positive. 

The authors note that the digitalis compounds are phytoestrogens and bind to oestrogen receptors.  Gynaecomastia is an adverse effect of chronic digitalis therapy and some studies have suggested that use of such treatment may increase risk of breast cancer; although most have either dismissed the importance of their findings or found them not to be statistically significant.

Researchers conducted this study to test the hypothesis that the oestrogenic effects of digoxin may increase the risk of breast cancer among users, by examining the association between digoxin use and the incidence of breast cancer in Danish women.  They identified women using digoxin and angina drugs from the Danish Prescription Database; the latter were included to determine whether being under care for heart disease could have influenced the findings.  Cases of breast cancer were identified from the Danish Cancer Registry. 

The main findings reported were as follows:

• Of 104,648 women using digoxin included in the analysis, 2,144 developed breast cancer. Among the 137,493 exposed to angina drugs only (a comparison group with cardiovascular disease), there were 2,658 cases of breast cancer.

• Current digoxin users were at increased risk of breast cancer (RR 1.39; 95% CI 1.32 to 1.46); this risk was slightly higher for women with 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).

• There was no increased risk seen for former users of digoxin (RR 0.91; 95% CI 0.83 to 1.00).

• Use of angina drugs was not associated with an increased risk of breast cancer, either with current or former use.

The authors comment that their results provide ‘convincing evidence’ that current digoxin use significantly increases the risks of breast cancers; this risk normalizes rapidly following its discontinuation.   They say that although the effect observed was similar to that of postmenopausal oestrogens, “it was nevertheless small, and the importance of digoxin to the clinical management of heart disease may outweigh our inferences regarding increased risks of breast cancer.”