Is digoxin a breast cancer risk factor?

Abstract

Th e review of the literature regarding the association between digoxin and the development of breast cancer has remained controversial. Several observational studies have reported that the use of digoxin was associated with an increased risk of breast cancer. In a letter published in 1979, Stenkvist et al. (10) suggested that digoxin is associated with less aggressive breast tumor phenotypes and a lower risk of metastasis. Later, in 1999, the same investigators confi rmed their fi ndings in another report (11). Th is letter was followed by other reports, including two independent Danish studies that reported up to 30% increased breast cancer risk among digoxin users compared with non-users. However, these studies were limited by the inability to address the eff ects of confounding factors such as lifestyle-related risk factors and screening mammography (12 – 16). In order to overcome the above-mentioned shortcomings in these retrospective studies, Ahern et al., 2014 (17) studied the association of digoxin and breast cancer in the nurses ’ health study cohort. Th e authors in this study followed 90 202 post-menopausal women from 1994 – 2010, and assessed the incidence of breast cancer, overall and by their ER status, accounting for screening mammography and established breast cancer risk factors. It was found that digoxin use of less than four-years duration was associated with a 45% increased rate of breast cancer, compared with those women who did not use digoxin. Th is association was stronger for ER-positive tumors and had taken into account lifestyle risk factors and screening practices. In this study, it was noted that digoxin users were more likely to undergo screening mammography, and to be former users of postmenopausal hormones, and have similar reproductive history and rates of alcohol consumption. Th e suggested hypothesis from the observed association of digoxin use and increased incidence of ER-positive breast cancer stems from an estrogen-mimetic action of digoxin. It appears that digoxin acts through estrogen signaling pathways in promoting breast tumor growth. Th is hypothesis is supported by the fact that digoxin interacts with human estrogen receptors in vitro (18). Th is pattern is similar to those who have increased breast cancer risk due to exogenous hormone use. In addition, digoxin is associated with gynecomastia in males, an increased incidence of male breast cancer, and increased incidence of uterine cancer, a hormone sensitive malignancy (19 – 22). Acute Cardiac Care, 2015; 17: 29–31 Copyright © 2015 Informa UK, Ltd ISSN 1748-2941 print/ISSN 1748-295X online DOI: 10.3109/17482941.2015.1066823