School of Population Health, Faculty of Health Sciences, Curtin University, Perth, Western Australia, Australia.
School of Population Health, Faculty of Health Sciences, Curtin University, Perth, Western Australia, Australia
BMJ Open. 2024 Mar 8;14(3):e080982. doi: 10.1136/bmjopen-2023-080982.
Calcium channel blockers (CCB), a commonly prescribed antihypertensive (AHT) medicine, may be associated with increased risk of breast cancer. The proposed study aims to examine whether long-term CCB use is associated with the development of breast cancer and to characterise the dose-response nature of any identified association, to inform future hypertension management.
The study will use data from 2 of Australia's largest cohort studies; the Australian Longitudinal Study on Women's Health, and the 45 and Up Study, combined with the Rotterdam Study. Eligible women will be those with diagnosed hypertension, no history of breast cancer and no prior CCB use at start of follow-up (2004-2009). Cumulative dose-duration exposure to CCB and other AHT medicines will be captured at the earliest date of: the outcome (a diagnosis of invasive breast cancer); a competing risk event (eg, bilateral mastectomy without a diagnosis of breast cancer, death prior to any diagnosis of breast cancer) or end of follow-up (censoring event). Fine and Gray competing risks regression will be used to assess the association between CCB use and development of breast cancer using a generalised propensity score to adjust for baseline covariates. Time-varying covariates related to interaction with health services will also be included in the model. Data will be harmonised across cohorts to achieve identical protocols and a two-step random effects individual patient-level meta-analysis will be used.
Ethical approval was obtained from the following Human research Ethics Committees: Curtin University (ref No. HRE2022-0335), NSW Population and Health Services Research Ethics Committee (2022/ETH01392/2022.31), ACT Research Ethics and Governance Office approval under National Mutual Acceptance for multijurisdictional data linkage research (2022.STE.00208). Results of the proposed study will be published in high-impact journals and presented at key scientific meetings.
NCT05972785.
钙通道阻滞剂（CCB）是一种常用的降压药物，可能与乳腺癌风险增加有关。本研究旨在探讨长期使用 CCB 是否与乳腺癌的发生有关，并描述任何已识别关联的剂量反应性质，以为未来的高血压管理提供信息。
本研究将使用澳大利亚两项最大的队列研究（澳大利亚妇女健康纵向研究和 45 岁及以上研究）的数据，以及荷兰研究的数据进行分析。符合条件的女性为诊断为高血压、无乳腺癌病史且在随访开始时（2004-2009 年）未使用过 CCB 的女性。将最早记录的以下日期的 CCB 和其他降压药物的累积剂量-持续时间暴露情况作为暴露变量：结局（浸润性乳腺癌的诊断）；竞争风险事件（例如，双侧乳房切除术但无乳腺癌诊断、乳腺癌诊断前死亡）或随访结束（删失事件）。Fine 和 Gray 竞争风险回归将用于评估 CCB 使用与乳腺癌发展之间的关联，使用广义倾向评分调整基线协变量。还将在模型中纳入与卫生服务交互相关的时变协变量。将对各队列的数据进行协调，以实现完全一致的方案，并使用两步随机效应个体患者水平荟萃分析。
以下人类研究伦理委员会已批准本研究：科廷大学（编号 HRE2022-0335）、新南威尔士州人口和卫生服务研究伦理委员会（2022/ETH01392/2022.31）、ACT 研究伦理和治理办公室批准的多司法管辖区数据链接研究的国家相互接受（2022.STE.00208）。本研究的结果将发表在高影响力期刊上，并在重要的科学会议上展示。
NCT05972785。
