British Heart Foundation Cardiovascular Epidemiology Unit, Department of Public Health and Primary Care, University of Cambridge, Cambridge, UK.
Department of Public Health and Primary Care, University of Cambridge, Cambridge, UK.
Breast Cancer Res. 2021 Sep 30;23(1):94. doi: 10.1186/s13058-021-01465-0.
Advancements in cancer therapeutics have resulted in increases in cancer-related survival; however, there is a growing clinical dilemma. The current balancing of survival benefits and future cardiotoxic harms of oncotherapies has resulted in an increased burden of cardiovascular disease in breast cancer survivors. Risk stratification may help address this clinical dilemma. This study is the first to assess the association between a coronary artery disease-specific polygenic risk score and incident coronary artery events in female breast cancer survivors.
We utilized the Studies in Epidemiology and Research in Cancer Heredity prospective cohort involving 12,413 women with breast cancer with genotype information and without a baseline history of cardiovascular disease. Cause-specific hazard ratios for association of the polygenic risk score and incident coronary artery disease (CAD) were obtained using left-truncated Cox regression adjusting for age, genotype array, conventional risk factors such as smoking and body mass index, as well as other sociodemographic, lifestyle, and medical variables.
Over a median follow-up of 10.3 years (IQR: 16.8) years, 750 incident fatal or non-fatal coronary artery events were recorded. A 1 standard deviation higher polygenic risk score was associated with an adjusted hazard ratio of 1.33 (95% CI 1.20, 1.47) for incident CAD.
This study provides evidence that a coronary artery disease-specific polygenic risk score can risk-stratify breast cancer survivors independently of other established cardiovascular risk factors.
癌症治疗的进步导致癌症相关的生存率提高；然而，这也带来了一个日益严重的临床困境。目前，癌症治疗的生存获益与未来的心脏毒性危害之间的平衡，导致乳腺癌幸存者的心血管疾病负担增加。风险分层可能有助于解决这一临床困境。本研究首次评估了冠状动脉疾病特异性多基因风险评分与女性乳腺癌幸存者中冠状动脉事件发生之间的相关性。
我们利用了包括 12413 名女性乳腺癌患者的前瞻性队列研究，这些患者具有基因型信息且没有心血管疾病的基线病史。使用左截断 Cox 回归，根据年龄、基因芯片、吸烟和体重指数等常规风险因素以及其他社会人口统计学、生活方式和医学变量，对多基因风险评分与冠状动脉疾病（CAD）发病风险的关联进行了因果风险比分析。
在中位随访 10.3 年（IQR：16.8）期间，记录了 750 例致命或非致命性冠状动脉事件。多基因风险评分每增加一个标准差，与 CAD 发病的校正风险比为 1.33（95%CI 1.20，1.47）。
本研究提供了证据表明，冠状动脉疾病特异性多基因风险评分可以独立于其他已确立的心血管风险因素对乳腺癌幸存者进行风险分层。
