Digoxin use and risk of invasive breast cancer: Evidence from the Nurses' Health Study and meta-analysis

Breast Cancer Research and Treatment (Impact Factor: 3.94). 02/2014; 144(2). DOI: 10.1007/s10549-014-2886-x
Source: PubMed


Despite preclinical evidence supporting anti-cancer effects of cardiac glycosides, epidemiologic studies consistently show elevated breast cancer risk in digoxin users. We studied this association in the Nurses' Health Study cohort to evaluate influences of screening mammography and lifestyle-related risk factors. We followed 90,202 postmenopausal women from 1994 to 2010. Self-reported breast cancers were confirmed by medical record review. We fit Cox regression models to estimate associations between time-varying digoxin use and breast cancer incidence, overall and by tumor ER status, accounting for mammography screening and established breast cancer risk factors. There were 5,004 digoxin users over 1.05 million person-years of observation, among whom 144 breast cancer cases occurred. Digoxin users were more likely to undergo mammographic screening, to be former users of postmenopausal hormones, and to take other medications than never-users; the groups were similar on reproductive history and alcohol consumption. Current digoxin use of >4-year duration was associated with a 45 % increased rate of breast cancer compared with never use (HRadj = 1.45, 95 % CI 1.13-1.86). The association appeared stronger for ER-positive disease (HRadj = 1.46, 95 % CI 1.10-1.95) than for ER-negative disease (HRadj = 1.12, 95 % CI 0.52-2.37). Associations were robust to restriction on regular mammography use and to adjustment for established breast cancer risk factors, including lifestyle-related exposures. The positive association between digoxin use and breast cancer occurrence was not attenuated when lifestyle-related breast cancer risk factors and screening practices were accounted for. Digoxin, a common cardiac drug worldwide, may promote breast carcinogenesis.

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    • "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. "

    Acute Cardiac Care 08/2015; 17(2). DOI:10.3109/17482941.2015.1066823
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    • "Due to their ability to bind to estrogen receptors, [3] there has been interest in assessing whether the use of CGs is associated with the incidence of breast cancer. [4–9] Namely, two case–control studies found that the use of digoxin was associated with an increased risk of breast cancer (RR: 1.30, 95% CI: 1.14-1.48 and RR: 1.39, 95% CI: 1.32-1.46), "
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    ABSTRACT: Background Two studies have reported statistically significant associations between the use of cardiac glycosides (CGs) and an increased risk of lung cancer. However, these studies had a number of methodological limitations. Thus, the objective of this study was to assess this association in a large population-based cohort of patients. Methods We used the United Kingdom Clinical Practice Research Datalink (CPRD) to identify a cohort of patients, at least 40 years of age, newly-diagnosed with heart failure, or supra-ventricular arrhythmia. A nested case–control analysis was conducted where each incident case of lung cancer identified during follow-up was randomly matched with up to 10 controls. Exposure to CGs was assessed in terms of ever use, cumulative duration of use and cumulative dose. Rate ratios (RRs) with 95% confidence intervals (CIs) were estimated using conditional logistic regression after adjusting for potential confounders. Results A total of 129,002 patients were included, and followed for a mean (SD) of 4.7 (3.8) years. During follow-up, 1237 patients were newly-diagnosed with lung cancer. Overall, ever use of CGs was not associated with an increased risk of lung cancer when compared to never use (RR = 1.09, 95% CI: 0.94-1.26). In addition, no dose–response relationship was observed in terms of cumulative duration of use and cumulative dose with all RRs around the null value across quartile categories. Conclusion The results of this large population-based study indicate that the use of CGs is not associated with an increased risk of lung cancer.
    BMC Cancer 08/2014; 14(1):573. DOI:10.1186/1471-2407-14-573 · 3.36 Impact Factor
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    ABSTRACT: Breast cancer is the second most common cause of death from cancer among women. Lifestyle changes are shown to be important in the prevention of breast cancer. Diet, physical activity, smoking, alcohol use, and vitamin and mineral use are key factors influencing the risk of breast cancer among women. Because these factors are related to each other, it is difficult to assess their individual roles in breast cancer. Some of these factors are alterable, meaning that women can decrease their risk for breast cancer by changing their behavior. Breast cancer is associated with a high rate of mortality and morbidity among women. Therefore, it is logical to try to find ways to decrease the risk of developing breast cancer. Lifestyle changes seem to be an easy, effective, and economical way to help prevention breast cancer. In women with a confirmed breast cancer diagnosis who are under radiotherapy treatment after undergoing a mastectomy, lifestyle changes are still very important. Some factors, such as smoking cessation and prevention of weight gain, may improve the long-term survival chances of these patients. Therefore, ways to increase women's knowledge about the role of lifestyle changes in the prevention of breast cancer and in the survival of patients with diagnosed breast cancer should be considered and studied.
    Electronic Physician 07/2014; 6(3):894-905. DOI:10.14661/2014.894-905
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