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利用医疗管理数据评估癌症药物重新利用的机会:使用β受体阻滞剂治疗乳腺癌的可能性。

Using administrative healthcare data to evaluate drug repurposing opportunities for cancer: the possibility of using beta-blockers to treat breast cancer.

作者信息

Tan George S Q, Botteri Edoardo, Wood Stephen, Sloan Erica K, Ilomäki Jenni

机构信息

Centre for Medicine Use and Safety, Monash University, Parkville, VIC, Australia.

Section for Colorectal Cancer Screening, Cancer Registry of Norway, Oslo, Norway.

出版信息

Front Pharmacol. 2023 Aug 10;14:1227330. doi: 10.3389/fphar.2023.1227330. eCollection 2023.

Abstract

Cancer registries and hospital electronic medical records are commonly used to investigate drug repurposing candidates for cancer. However, administrative data are often more accessible than data from cancer registries and medical records. Therefore, we evaluated if administrative data could be used to evaluate drug repurposing for cancer by conducting an example study on the association between beta-blocker use and breast cancer mortality. A retrospective cohort study of women aged ≥50 years with incident breast cancer was conducted using a linked dataset with statewide hospital admission data and nationwide medication claims data. Women receiving beta blockers and first-line anti-hypertensives prior to and at diagnosis were compared. Breast cancer molecular subtypes and metastasis status were inferred by algorithms from commonly prescribed breast cancer antineoplastics and hospitalization diagnosis codes, respectively. Subdistribution hazard ratios (sHR) and corresponding 95% confidence intervals (CIs) for breast cancer mortality were estimated using Fine and Gray's competing risk models adjusted for age, Charlson comorbidity index, congestive heart failure, myocardial infraction, molecular subtype, presence of metastasis at diagnosis, and breast cancer surgery. 2,758 women were hospitalized for incident breast cancer. 604 received beta-blockers and 1,387 received first-line antihypertensives. In total, 154 breast cancer deaths were identified over a median follow-up time of 2.7 years. We found no significant association between use of any beta-blocker and breast-cancer mortality (sHR 0.86, 95%CI 0.58-1.28), or when stratified by beta-blocker type (non-selective, sHR 0.42, 95%CI 0.14-1.25; selective, sHR 0.95, 95%CI 0.63-1.43). Results were not significant when stratified by molecular subtypes (e.g., triple negative breast cancer (TNBC), any beta blocker, sHR 0.16, 95%CI 0.02-1.51). It is possible to use administrative data to explore drug repurposing opportunities. Although non-significant, an indication of an association was found for the TNBC subtype, which aligns with previous studies using registry data. Future studies with larger sample size, longer follow-up are required to confirm the association, and linkage to clinical data sources are required to validate our methodologies.

摘要

癌症登记处和医院电子病历常用于研究癌症的药物重新利用候选药物。然而,行政数据通常比癌症登记处和病历中的数据更容易获取。因此,我们通过对β受体阻滞剂使用与乳腺癌死亡率之间的关联进行实例研究,评估行政数据是否可用于评估癌症的药物重新利用。使用一个包含全州医院入院数据和全国药物报销数据的链接数据集,对年龄≥50岁的新发乳腺癌女性进行了一项回顾性队列研究。比较了在诊断前及诊断时接受β受体阻滞剂和一线抗高血压药物治疗的女性。分别通过常用的乳腺癌抗肿瘤药物算法和住院诊断代码推断乳腺癌分子亚型和转移状态。使用Fine和Gray的竞争风险模型,对年龄、Charlson合并症指数、充血性心力衰竭、心肌梗死、分子亚型、诊断时的转移情况和乳腺癌手术进行调整,估计乳腺癌死亡率的亚分布风险比(sHR)和相应的95%置信区间(CI)。2758名女性因新发乳腺癌住院。604人接受了β受体阻滞剂治疗,1387人接受了一线抗高血压药物治疗。在中位随访时间2.7年期间,共确定了154例乳腺癌死亡病例。我们发现,使用任何β受体阻滞剂与乳腺癌死亡率之间均无显著关联(sHR 0.86,95%CI 0.58 - 1.28),按β受体阻滞剂类型分层时也无显著关联(非选择性,sHR 0.42,95%CI 0.14 - 1.25;选择性,sHR 0.95,95%CI 0.63 - 1.43)。按分子亚型分层时结果也无显著差异(例如,三阴性乳腺癌(TNBC),任何β受体阻滞剂,sHR 0.16,95%CI 0.02 - 1.51)。利用行政数据探索药物重新利用机会是可行的。虽然结果不显著,但在TNBC亚型中发现了一种关联迹象,这与之前使用登记数据的研究一致。需要进行更大样本量、更长随访时间的未来研究来证实这种关联,并且需要与临床数据源建立联系以验证我们的方法。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/fe20/10448902/6189902a63e2/fphar-14-1227330-g001.jpg

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