{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,1,27]],"date-time":"2026-01-27T21:49:46Z","timestamp":1769550586586,"version":"3.49.0"},"reference-count":31,"publisher":"Springer Science and Business Media LLC","issue":"6","license":[{"start":{"date-parts":[[2008,12,3]],"date-time":"2008-12-03T00:00:00Z","timestamp":1228262400000},"content-version":"tdm","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/2.0\/"},{"start":{"date-parts":[[2008,12,3]],"date-time":"2008-12-03T00:00:00Z","timestamp":1228262400000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/2.0\/"}],"content-domain":{"domain":["link.springer.com"],"crossmark-restriction":false},"short-container-title":["Breast Cancer Res"],"abstract":"<jats:title>Abstract<\/jats:title><jats:sec>\n                        <jats:title>Introduction<\/jats:title>\n                        <jats:p>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.<\/jats:p>\n                     <\/jats:sec><jats:sec>\n                        <jats:title>Methods<\/jats:title>\n                        <jats:p>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.<\/jats:p>\n                     <\/jats:sec><jats:sec>\n                        <jats:title>Results<\/jats:title>\n                        <jats:p>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.<\/jats:p>\n                     <\/jats:sec><jats:sec>\n                        <jats:title>Conclusions<\/jats:title>\n                        <jats:p>Our results suggest that digoxin treatment increases the risk of invasive breast cancer among postmenopausal women.<\/jats:p>\n                     <\/jats:sec>","DOI":"10.1186\/bcr2205","type":"journal-article","created":{"date-parts":[[2008,12,4]],"date-time":"2008-12-04T19:14:53Z","timestamp":1228418093000},"update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":57,"title":["Digoxin treatment is associated with an increased incidence of breast cancer: a population-based case-control study"],"prefix":"10.1186","volume":"10","author":[{"given":"Thomas P","family":"Ahern","sequence":"first","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Timothy L","family":"Lash","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Henrik T","family":"S\u00f8rensen","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Lars","family":"Pedersen","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"297","published-online":{"date-parts":[[2008,12,3]]},"reference":[{"key":"2169_CR1","first-page":"1264","volume-title":"Harrison's Principles of Internal Medicine","author":"TR Harrison","year":"1998","unstructured":"Harrison TR, Fauci AS: Harrison's Principles of Internal Medicine. 1998, New York, NY: McGraw-Hill, Health Professions Division, 1264-1295. 14","edition":"14"},{"key":"2169_CR2","doi-asserted-by":"publisher","first-page":"563","DOI":"10.1016\/S0140-6736(79)90996-6","volume":"1","author":"B Stenkvist","year":"1979","unstructured":"Stenkvist B, Bengtsson E, Eriksson O, Holmquist J, Nordin B, Westman-Naeser S: Cardiac glycosides and breast cancer. Lancet. 1979, 1: 563-10.1016\/S0140-6736(79)90996-6.","journal-title":"Lancet"},{"key":"2169_CR3","first-page":"484","volume":"306","author":"B Stenkvist","year":"1982","unstructured":"Stenkvist B, Pengtsson E, Dahlqvist B, Eriksson O, Jarkrans T, Nordin B: Cardiac glycosides and breast cancer, revisited. N Engl J Med. 1982, 306: 484-","journal-title":"N Engl J Med"},{"key":"2169_CR4","first-page":"493","volume":"6","author":"B Stenkvist","year":"1999","unstructured":"Stenkvist B: Is digitalis a therapy for breast carcinoma?. Oncol Rep. 1999, 6: 493-496.","journal-title":"Oncol Rep"},{"key":"2169_CR5","doi-asserted-by":"publisher","first-page":"1","DOI":"10.1007\/s10549-005-9053-3","volume":"96","author":"JQ Chen","year":"2006","unstructured":"Chen JQ, Contreras RG, Wang R, Fernandez SV, Shoshani L, Russo IH, Cereijido M, Russo J: Sodium\/potassium ATPase (Na+, K+-ATPase) and ouabain\/related cardiac glycosides: A new paradigm for development of anti- breast cancer drugs?. Breast Cancer Res Treat. 2006, 96: 1-15. 10.1007\/s10549-005-9053-3.","journal-title":"Breast Cancer Res Treat"},{"key":"2169_CR6","doi-asserted-by":"publisher","first-page":"36","DOI":"10.1124\/mi.8.1.8","volume":"8","author":"RA Newman","year":"2008","unstructured":"Newman RA, Yang P, Pawlus AD, Block KI: Cardiac glycosides as novel cancer therapeutic agents. Mol Interv. 2008, 8: 36-49. 10.1124\/mi.8.1.8.","journal-title":"Mol Interv"},{"key":"2169_CR7","doi-asserted-by":"publisher","first-page":"11","DOI":"10.1186\/1471-2407-1-11","volume":"1","author":"J Haux","year":"2001","unstructured":"Haux J, Klepp O, Spigset O, Tretli S: Digitoxin medication and cancer; case control and internal dose-response studies. BMC Cancer. 2001, 1: 11-10.1186\/1471-2407-1-11.","journal-title":"BMC Cancer"},{"key":"2169_CR8","doi-asserted-by":"publisher","first-page":"875","DOI":"10.1016\/S0140-6736(84)90915-2","volume":"2","author":"GD Friedman","year":"1984","unstructured":"Friedman GD: Digitalis and breast cancer. Lancet. 1984, 2: 875-10.1016\/S0140-6736(84)90915-2.","journal-title":"Lancet"},{"key":"2169_CR9","doi-asserted-by":"publisher","first-page":"813","DOI":"10.1136\/bmj.39507.551644.BE","volume":"336","author":"HT Sorensen","year":"2008","unstructured":"Sorensen HT, Christensen S, Mehnert F, Pedersen L, Chapurlat RD, Cummings SR, Baron JA: Use of bisphosphonates among women and risk of atrial fibrillation and flutter: population based case-control study. BMJ. 2008, 336: 813-816. 10.1136\/bmj.39507.551644.BE.","journal-title":"BMJ"},{"key":"2169_CR10","doi-asserted-by":"crossref","first-page":"594","DOI":"10.1038\/sj.bjc.6602313","volume":"92","author":"HT Sorensen","year":"2005","unstructured":"Sorensen HT, Skriver MV, Friis S, McLaughlin JK, Blot WJ, Baron JA: Use of antibiotics and risk of breast cancer: a population-based case-control study. Br J Cancer. 2005, 92: 594-596.","journal-title":"Br J Cancer"},{"key":"2169_CR11","doi-asserted-by":"publisher","first-page":"2398","DOI":"10.1126\/science.287.5462.2398","volume":"287","author":"L Frank","year":"2000","unstructured":"Frank L: Epidemiology. When an entire country is a cohort. Science. 2000, 287: 2398-2399. 10.1126\/science.287.5462.2398.","journal-title":"Science"},{"key":"2169_CR12","doi-asserted-by":"crossref","first-page":"1305","DOI":"10.1111\/j.1572-0241.2003.07459.x","volume":"98","author":"A Floyd","year":"2003","unstructured":"Floyd A, Pedersen L, Nielsen GL, Thorlacius-Ussing O, Sorensen HT: Risk of acute pancreatitis in users of azathioprine: a population-based case-control study. Am J Gastroenterol. 2003, 98: 1305-1308.","journal-title":"Am J Gastroenterol"},{"key":"2169_CR13","doi-asserted-by":"publisher","first-page":"616","DOI":"10.1038\/sj.bjc.6604533","volume":"99","author":"TL Lash","year":"2008","unstructured":"Lash TL, Pedersen L, Cronin-Fenton D, Ahern TP, Rosenberg CL, Lunetta KL, Silliman RA, Hamilton-Dutoit S, Garne JP, Ewertz M, S\u00f8rensen HT: Tamoxifen's protection against breast cancer recurrence is not reduced by concurrent use of the SSRI citalopram. Br J Cancer. 2008, 99: 616-621. 10.1038\/sj.bjc.6604533.","journal-title":"Br J Cancer"},{"key":"2169_CR14","unstructured":"World Health Organization: WHO Collaborating Center for Drug Statistics Methodology. [http:\/\/www.whocc.no\/atcddd\/]"},{"key":"2169_CR15","doi-asserted-by":"publisher","first-page":"1953","DOI":"10.1056\/NEJM200006293422604","volume":"342","author":"S Schulman","year":"2000","unstructured":"Schulman S, Lindmarker P: Incidence of cancer after prophylaxis with warfarin against recurrent venous thromboembolism. Duration of Anticoagulation Trial. N Engl J Med. 2000, 342: 1953-1958. 10.1056\/NEJM200006293422604.","journal-title":"N Engl J Med"},{"key":"2169_CR16","doi-asserted-by":"publisher","first-page":"927","DOI":"10.1111\/j.1365-2125.2008.03121.x","volume":"65","author":"P McGettigan","year":"2008","unstructured":"McGettigan P, Han P, Jones L, Whitaker D, Henry D: Selective COX-2 inhibitors, NSAIDs and congestive heart failure: differences between new and recurrent cases. Br J Clin Pharmacol. 2008, 65: 927-934. 10.1111\/j.1365-2125.2008.03121.x.","journal-title":"Br J Clin Pharmacol"},{"key":"2169_CR17","doi-asserted-by":"publisher","first-page":"1564","DOI":"10.1158\/1055-9965.EPI-07-2828","volume":"17","author":"KB Moysich","year":"2008","unstructured":"Moysich KB, Beehler GP, Zirpoli G, Choi JY, Baker JA: Use of common medications and breast cancer risk. Cancer Epidemiol Biomarkers Prev. 2008, 17: 1564-1595. 10.1158\/1055-9965.EPI-07-2828.","journal-title":"Cancer Epidemiol Biomarkers Prev"},{"key":"2169_CR18","doi-asserted-by":"publisher","first-page":"2433","DOI":"10.1001\/jama.291.20.2433","volume":"291","author":"MB Terry","year":"2004","unstructured":"Terry MB, Gammon MD, Zhang FF, Tawfik H, Teitelbaum SL, Britton JA, Subbaramaiah K, Dannenberg AJ, Neugut AI: Association of frequency and duration of aspirin use and hormone receptor status with breast cancer risk. JAMA. 2004, 291: 2433-2440. 10.1001\/jama.291.20.2433.","journal-title":"JAMA"},{"key":"2169_CR19","doi-asserted-by":"publisher","first-page":"2344","DOI":"10.1016\/j.ejca.2008.07.041","volume":"44","author":"J Cuzick","year":"2008","unstructured":"Cuzick J: Hormone replacement therapy and the risk of breast cancer. Eur J Cancer. 2008, 44: 2344-2349. 10.1016\/j.ejca.2008.07.041.","journal-title":"Eur J Cancer"},{"key":"2169_CR20","first-page":"111","volume-title":"Modern Epidemiology","author":"KJ Rothman","year":"2008","unstructured":"Rothman KJ, Greenland S, Lash TL: Case-control studies. Modern Epidemiology. 2008, Philadelphia, PA: Lippincott Williams & Wilkins, 111-125. 3","edition":"3"},{"key":"2169_CR21","first-page":"49","volume":"2","author":"B Stenkvist","year":"1980","unstructured":"Stenkvist B, Bengtsson E, Eklund G, Eriksson O, Holmquist J, Nordin B, Westman-Naeser S: Evidence of a modifying influence of heart glucosides on the development of breast cancer. Anal Quant Cytol. 1980, 2: 49-54.","journal-title":"Anal Quant Cytol"},{"key":"2169_CR22","doi-asserted-by":"publisher","first-page":"467","DOI":"10.1080\/028418601750288181","volume":"40","author":"M Ewertz","year":"2001","unstructured":"Ewertz M, Holmberg L, Tretli S, Pedersen BV, Kristensen A: Risk factors for male breast cancer \u2013 a case-control study from Scandinavia. Acta Oncol. 2001, 40: 467-471. 10.1080\/028418601750288181.","journal-title":"Acta Oncol"},{"key":"2169_CR23","doi-asserted-by":"publisher","first-page":"204","DOI":"10.1016\/S0140-6736(79)91475-2","volume":"2","author":"DH Cove","year":"1979","unstructured":"Cove DH, Barker GA: Digoxin and hormone receptors. Lancet. 1979, 2: 204-10.1016\/S0140-6736(79)91475-2.","journal-title":"Lancet"},{"key":"2169_CR24","doi-asserted-by":"publisher","first-page":"1","DOI":"10.1016\/j.toxlet.2004.06.014","volume":"155","author":"A Freyberger","year":"2005","unstructured":"Freyberger A, Schmuck G: Screening for estrogenicity and anti-estrogenicity: a critical evaluation of an MVLN cell-based transactivation assay. Toxicol Lett. 2005, 155: 1-13. 10.1016\/j.toxlet.2004.06.014.","journal-title":"Toxicol Lett"},{"key":"2169_CR25","doi-asserted-by":"publisher","first-page":"489","DOI":"10.1111\/j.1749-6632.2003.tb07233.x","volume":"986","author":"O Aizman","year":"2003","unstructured":"Aizman O, Aperia A: Na, K-ATPase as a signal transducer. Ann NY Acad Sci. 2003, 986: 489-496.","journal-title":"Ann NY Acad Sci"},{"key":"2169_CR26","doi-asserted-by":"publisher","first-page":"2093","DOI":"10.1016\/j.lfs.2007.03.013","volume":"80","author":"M Nesher","year":"2007","unstructured":"Nesher M, Shpolansky U, Rosen H, Lichtstein D: The digitalis-like steroid hormones: new mechanisms of action and biological significance. Life Sci. 2007, 80: 2093-2107. 10.1016\/j.lfs.2007.03.013.","journal-title":"Life Sci"},{"key":"2169_CR27","doi-asserted-by":"publisher","first-page":"1091","DOI":"10.1210\/endo-99-4-1091","volume":"99","author":"SM Rifka","year":"1976","unstructured":"Rifka SM, Pita JC, Loriaux DL: Mechanism of interaction of digitalis with estradiol binding sites in rat uteri. Endocrinology. 1976, 99: 1091-1096.","journal-title":"Endocrinology"},{"key":"2169_CR28","first-page":"134","volume-title":"Modern Epidemiology","author":"KJ Rothman","year":"2008","unstructured":"Rothman KJ, Greenland S, Lash TL: Validity in epidemiologic studies. Modern Epidemiology. 2008, Philadelphia: Lippincott Williams & Wilkins, 134-137. 3","edition":"3"},{"key":"2169_CR29","doi-asserted-by":"publisher","first-page":"131","DOI":"10.1186\/bcr1029","volume":"7","author":"J Russo","year":"2005","unstructured":"Russo J, Moral R, Balogh GA, Mailo D, Russo IH: The protective role of pregnancy in breast cancer. Breast Cancer Res. 2005, 7: 131-142. 10.1186\/bcr1029.","journal-title":"Breast Cancer Res"},{"key":"2169_CR30","doi-asserted-by":"publisher","first-page":"72","DOI":"10.1007\/978-0-387-78818-0_6","volume":"630","author":"A Hjartaker","year":"2008","unstructured":"Hjartaker A, Langseth H, Weiderpass E: Obesity and diabetes epidemics: cancer repercussions. Adv Exp Med Biol. 2008, 630: 72-93.","journal-title":"Adv Exp Med Biol"},{"key":"2169_CR31","doi-asserted-by":"publisher","first-page":"663","DOI":"10.1016\/j.ecl.2008.06.004","volume":"37","author":"KC Zalesin","year":"2008","unstructured":"Zalesin KC, Franklin BA, Miller WM, Peterson ED, McCullough PA: Impact of obesity on cardiovascular disease. Endocrinol Metab Clin North Am. 2008, 37: 663-684. 10.1016\/j.ecl.2008.06.004.","journal-title":"Endocrinol Metab Clin North Am"}],"container-title":["Breast Cancer Research"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/link.springer.com\/content\/pdf\/10.1186\/bcr2205.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/link.springer.com\/article\/10.1186\/bcr2205\/fulltext.html","content-type":"text\/html","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/link.springer.com\/content\/pdf\/10.1186\/bcr2205.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2024,10,8]],"date-time":"2024-10-08T10:49:17Z","timestamp":1728384557000},"score":1,"resource":{"primary":{"URL":"https:\/\/breast-cancer-research.biomedcentral.com\/articles\/10.1186\/bcr2205"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2008,12,3]]},"references-count":31,"journal-issue":{"issue":"6","published-online":{"date-parts":[[2008,12]]}},"alternative-id":["2169"],"URL":"https:\/\/doi.org\/10.1186\/bcr2205","relation":{},"ISSN":["1465-542X"],"issn-type":[{"value":"1465-542X","type":"electronic"}],"subject":[],"published":{"date-parts":[[2008,12,3]]},"assertion":[{"value":"18 August 2008","order":1,"name":"received","label":"Received","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"12 November 2008","order":2,"name":"revised","label":"Revised","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"3 December 2008","order":3,"name":"accepted","label":"Accepted","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"3 December 2008","order":4,"name":"first_online","label":"First Online","group":{"name":"ArticleHistory","label":"Article History"}}],"article-number":"R102"}}