Digoxin, a medication used to treat heart failure and irregular heart beat, has estrogenic properties. It has been shown to increase risk of breast cancer in both women and men. Laboratory studies show that digoxin has some anti-cancer properties, which have not been fully explained. Now a new article has summarized digoxin's cancer promoting effects in women.

Digoxin has estrogenic properties

Digoxin was originally derived from the foxglove (digitalis) plant. Digoxin is chemically similar to estrogen and appears to have estrogenic effects. For example, it can cause enlarged breasts (gynaecomastia) in men. Digoxin has also been shown to reduce prostate cancer in men, which is consistent with having estrogenic properties. Despite this, digoxin is sometimes prescribed for breast cancer survivors with chemotherapy-induced heart damage.

Digoxin increases breast cancer risk in women and men

Several Scandinavian studies have reported that digoxin use is associated with increased risk of breast cancer in women. For example, a 2011 Danish study of 104,648 women using digoxin reported that current digoxin users had 1.4 times the risk of breast cancer of non-users. However, breast cancer risk was not higher among former digoxin users. The increased risk in digoxin users was marginally higher for estrogen receptor positive (ER+) than for ER- breast cancer. Digoxin also increased the risk of uterine cancers (endometrial cancer and uterine sarcoma) in the same study population.

A study that was designed to determine breast cancer risk factors among Scandinavian men reported that men using digoxin had twice the risk of breast cancer as those who did not. The increased risk associated with digoxin was similar to the increased risk conferred by obesity, a known risk factor for male breast cancer.

Laboratory studies show that digoxin has some anti-cancer properties

Digoxin has been found to have anti-cancer activities in the laboratory, although the mechanism of action is not well understood. Digoxin has been shown to inhibit both primary tumor growth and the metastasis of breast cancer cells to the lungs in a mouse model of breast cancer. However, it is not clear that the anticancer effects of digoxin observed in mice are relevant in humans. Digoxin has been shown to increase apoptosis (programmed cell death) in triple negative breast cancer cells. One study reported that the combination of digoxin and Taxol might be a more effective treatment for ER- breast cancer than Taxol alone. These experimental findings might eventually lead to the development of an effective anti-cancer drug. However, in the mean time, population studies showing that digoxin increases breast cancer risk (including risk of ER- disease) indicate that this drug might not be safe for breast cancer survivors and those at high risk for breast cancer.

Latest article summarizes digoxin's cancer promoting effects

The review referenced at the beginning of this news story summarizes the evidence for an association between use of digoxin and estrogen-sensitive cancers. Women currently using digoxin have elevated risks of breast and uterine cancer, however, the cancer risks fall off quickly after digoxin treatment ends. This pattern is reminiscent of estrogen, indicating that digoxin induces proliferation of breast cells and promotes the growth of small or incipient tumors. The author suggests that other estrogen-like drugs, particularly spironolactone (Aldactone), should be investigated for similar effects.

There is no data concerning the effect of digoxin use in breast cancer patients undergoing treatment or breast cancer survivors. The breast cancer recurrence risk of women with ER+ breast cancer who are taking tamoxifen might not be greatly affected by taking digoxin since tamoxifen blocks estrogen receptors. However, risk could increase among women taking aromatase inhibitors since aromatase inhibitors interfere with estrogen production while leaving estrogen receptors susceptible to digoxin. The author suggests that, if adverse effects are proven, women taking digoxin would be better off taking tamoxifen rather than an aromatase inhibitor or else using other heart medications. However, it is possible that digoxin use would amplify the increased risk of uterine cancer caused by tamoxifen use.