背景：实验室和流行病学研究表明，强心苷具有修饰作用（例如，地高辛和洋地黄毒苷)对癌症风险的影响。我们探讨了地高辛治疗与绝经后丹麦女性浸润性乳腺癌发病率之间的关系。
方法：我们使用丹麦登记处对1991年1月1日至2007年12月31日期间诊断为浸润性乳腺癌的5,565名绝经后妇女和55,650名匹配的对照人群进行了鉴定。从县处方登记处确定了强心苷处方。所有受试者具有至少2年的记录的处方药和病史数据。我们在调整年龄的条件逻辑回归模型中估计地高辛使用与乳腺癌相关的比值比，县的居住，使用抗凝剂，非甾体抗炎药（NSAIDs），阿司匹林,激素替代疗法.我们还探讨了适应症和检测偏差混淆的影响。
结果：地高辛是研究期间向受试者开出的唯一强心苷。有324例乳腺癌病例（5.8％）和2,546例对照（4.6％）在其索引日期前至少1年有地高辛使用史（调整后的比值比（OR）：1.30；95％置信区间：1.14至1.48）。乳腺癌OR随着地高辛暴露时间的增加而适度增加（地高辛使用7至18年的校正OR：1.39；95％置信区间：1.10至1.74）。这种关联对年龄的调整是稳健的，接受激素替代疗法,共同处方药物，通过指示混淆。病例和对照组之间的筛查乳房X光检查率的比较没有发现检测偏倚的证据。
结论：我们的研究结果表明，地高辛治疗会增加绝经后女性患浸润性乳腺癌的风险。
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.
PDF(Sci-hub)