Digoxin use and risk of invasive breast cancer: evidence from the Nurses' Health Study and meta-analysis.
Digoxin use and risk of invasive breast cancer: evidence from the Nurses' Health Study and meta-analysis.
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DOI：
10.1007/s10549-014-2886-x
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发表时间：
2014-04
影响因子：
3.8
通讯作者：
Hankinson SE
中科院分区：
文献类型：
--
作者：
Ahern TP;Tamimi RM;Rosner BA;Hankinson SE
尽管临床前证据支持强心苷的抗癌作用，但流行病学研究一致显示地高辛使用者的乳腺癌风险升高。我们在护士健康研究队列中研究了这种关联，以评估筛查性乳房X光检查和生活方式相关危险因素的影响。我们从1994年到2010年跟踪了90,202名绝经后妇女。自我报告的乳腺癌通过病历审查得到证实。我们拟合考克斯回归模型，以估计随时间变化的地高辛使用与乳腺癌发病率之间的相关性，总体和肿瘤ER状态，考虑乳房X线检查筛查和确定的乳腺癌风险因素。在超过105万人年的观察中，有5，004名地高辛使用者，其中144名发生乳腺癌病例。地高辛使用者更有可能接受乳房X线筛查，是绝经后激素的前使用者，并且比从未使用者服用其他药物;这两组在生育史和饮酒方面相似。与从未使用地高辛相比，目前使用地高辛超过4年的患者乳腺癌发生率增加45%（HRadj=1.45，95%CI：1.13，1.86）。与ER阴性疾病（HRadj= 1.12，95%CI：0.52，2.37）相比，ER阳性疾病（HRadj =1.46，95%CI：1.10，1.95）的相关性似乎更强。限制常规乳房X光检查的使用和调整已确定的乳腺癌风险因素（包括生活方式相关的暴露）之间的关联很强。当考虑到生活方式相关的乳腺癌危险因素和筛查实践时，地高辛使用与乳腺癌发生之间的正相关性并未减弱。地高辛是世界范围内常用的心脏药物，可能促进乳腺癌的发生。
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 until 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 years’ 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.