A Danish study has found that women taking the heart drug digoxin (digitalis) had a nearly 40% increased risk of contracting breast cancer.

There are two reasons that the increase in cancer risk is thought to be due to the digoxin itself and not some other factor: First, the increased risk was seen only in current digoxin users, not in former users; and second, the increased risk was not seen in patients taking angina drugs, meaning that it was probably not caused by heart disease.

The risks to digoxin users were higher for ER (estrogen receptor)-positive cancers than for ER-negative cancers.

Digoxin is most often prescribed to patients with congestive heart failure or with rhythmic abnormalities such as atrial fibrillation. It makes the heart beat more efficiently, increasing blood flow to the rest of the body. It also helps control heart rate and rhythm.

The study looked at drug prescription and cancer incidence in Denmark between 1995 and 2008, using national databases. It found that current digoxin users had a 39% higher relative risk of developing breast cancer, but former users showed no risk increase. In other words, the risk disappeared once patients stopped taking digoxin.

To see if being under care for heart disease affected the breast cancer risk, the study also compared breast cancer incidence in users of angina drugs who did not take digoxin. They found no increase in breast cancer risk among current or former users of angina drugs.

In all, the study looked at over 100,000 women who had taken digoxin and over 100,000 women who had only taken angina drugs.

The study authors began their study because the chemical structure of digoxin resembles that of estrogen, so the two compounds may have similar effects. This was partially borne out by a closer look at the type of breast cancers found. The risks to digoxin users were higher for ER (estrogen receptor)-positive cancers than for ER-negative cancers. ER-positive breast cancers require estrogen to grow, while ER-negative cancers do not.

The study results were published online ahead of print on March 21, 2011 by the Journal of Clinical Oncology.