Digoxin treatment is associated with an increased incidence of breast cancer: a population-based case-control study.
BACKGROUND
Laboratory and epidemiologic studies have suggested a modifying effect of cardiac glycosides (for example, digoxin and digitoxin) on cancer risk. We explored the association between digoxin treatment and invasive breast cancer incidence among postmenopausal Danish women.


METHODS
We used Danish registries to identify 5,565 postmenopausal women diagnosed with incident invasive breast carcinoma between 1 January 1991 and 31 December 2007, and 55,650 matched population controls. Cardiac glycoside prescriptions were ascertained from county prescription registries. All subjects had at least 2 years of recorded prescription drug and medical history data. We estimated the odds ratio associating digoxin use with breast cancer in conditional logistic regression models adjusted for age, county of residence, and use of anticoagulants, non-steroidal anti-inflammatory drugs (NSAIDs), aspirin, and hormone replacement therapy. We also explored the impact of confounding by indication and detection bias.


RESULTS
Digoxin was the sole cardiac glycoside prescribed to subjects during the study period. There were 324 breast cancer cases (5.8%) and 2,546 controls (4.6%) with a history of digoxin use at least 1 year before their index date (adjusted odds ratio (OR): 1.30; 95% confidence interval: 1.14 to 1.48). The breast cancer OR increased modestly with increasing duration of digoxin exposure (adjusted OR for 7 to 18 years of digoxin use: 1.39; 95% confidence interval: 1.10 to 1.74). The association was robust to adjustment for age, receipt of hormone replacement therapy, coprescribed drugs, and confounding by indication. A comparison of screening mammography rates between cases and controls showed no evidence of detection bias.


CONCLUSIONS
Our results suggest that digoxin treatment increases the risk of invasive breast cancer among postmenopausal women.
Ahern
Thomas P
TP
Department of Clinical Epidemiology, Aarhus University Hospital, Olof Palmes Alle 43-45, 8200 Aarhus N, Denmark. tpa@bu.edu
Lash
Timothy L
TL
Sørensen
Henrik T
HT
Pedersen
Lars
L
D000368:Aged; D000369:Aged, 80 and over; D001943:Breast Neoplasms / Q000453:epidemiology*; D002316:Cardiotonic Agents / Q000627:therapeutic use*; D002318:Cardiovascular Diseases / Q000150:complications / Q000188:drug therapy; D016022:Case-Control Studies; D004074:Digitoxin / Q000627:therapeutic use; D004077:Digoxin / Q000627:therapeutic use*; D005260:Female; D006801:Humans; D015994:Incidence; D008875:Middle Aged; D017698:Postmenopause; D011446:Prospective Studies; D012307:Risk Factors
D002316:Cardiotonic Agents; D004077:Digoxin; D004074:Digitoxin