Predictors of CVD among breast cancer survivors in an integrated health system

项目摘要/摘要 乳腺癌幸存者患心血管疾病(CVD)的风险很高 乳腺癌的诊断，但风险增加的亚群和干预目标一直不好- 特色化的。越来越多的文献将心血管疾病与特定的心脏毒性癌症治疗联系起来。心血管疾病风险 乳腺癌存活者可能会因不坚持使用心血管药物和存在而有所不同 心血管疾病危险因素。然而，大多数关于乳腺癌患者人群心血管疾病风险的研究都 有很大的局限性，包括心血管疾病结局特征不佳，缺乏心血管疾病用药依从性 数据和风险因素，以及配对不佳的非癌症对照组。需要精心设计的研究来 确定乳腺癌幸存者的心血管事件高危亚群和可修改的目标 在考虑接受的特定乳腺癌治疗、心血管疾病药物和心血管疾病风险的同时进行干预 各种因素。我们建议在一项正在进行的乳腺癌幸存者研究中进行一项辅助研究，这将 克服以往研究的局限性。拟议的研究将全面检查临床和行为 乳腺癌幸存者心血管疾病预后的预测指标，并将最大限度地利用独特的患者和数据 可在凯撒永久北加州(KPNC)获得的资源。我们将比较CVD事件在 路径研究，一组年龄21岁的KPNC女性成员被诊断为浸润性乳腺癌 (n=4,453，R01CA105274)与新年龄、种族/民族、共病史和 KPNC成员与健康KPNC女性成员队列相匹配(n=22,265)。具体目标有：目标1) 检查发生心血管事件(缺血性心脏病、中风/一过性)的绝对风险和相对风险 缺血性发作、心肌病/心力衰竭等)和新发的心血管疾病危险因素(高血压、 糖尿病、血脂异常)乳腺癌妇女(路径)和非癌症对照组(KPNC) 配对队列)；目的2)在有乳腺癌病史的女性(路径)中，检查患乳腺癌的相对风险 按心脏毒性乳腺癌治疗类型划分的心血管事件和新发心血管疾病危险因素 接受治疗，包括化疗/生物治疗(蒽环类药物、曲妥扎单抗)、激素治疗 (他莫昔芬、芳香酶抑制剂)和放射治疗，控制与基线心血管疾病相关的混杂因素 服药依从性、临床和行为风险因素、医疗保健和保健系统因素，以及 社会经济地位(SES)；目的3)评估有以下病史的女性对心血管疾病药物的依从性 采用乳腺癌(通路)14年随访资料，并考察依从性与 控制接受心脏毒性癌症治疗的心血管事件的风险、心血管疾病临床和行为基线 风险因素、医疗和卫生保健系统因素以及社会经济状况。影响：这项研究的结果将产生 识别心血管疾病高危乳腺癌亚群和识别潜在风险的重要意义 干预目标，如服药依从性和控制心血管疾病危险因素。

PROJECT SUMMARY / ABSTRACT Breast cancer survivors are at high risk of developing and dying from cardiovascular disease (CVD) following breast cancer diagnosis, but subpopulations at increased risk and targets for intervention have not been well- characterized. A growing body of literature links CVD with specific cardiotoxic cancer treatments. CVD risk among breast cancer survivors might vary by concomitant non-adherence to CVD medications and presence of CVD risk factors. However, most of the studies on CVD risk among breast cancer patient populations have had significant limitations, including poorly characterized CVD outcomes, lack of CVD medication adherence data and risk factors, and poorly matched cancer-free control groups. Well-designed studies are needed to identify subpopulations of breast cancer survivors at high risk for CVD events and modifiable targets for intervention while accounting for specific breast cancer treatments received, CVD medications, and CVD risk factors. We propose to conduct an ancillary study within an ongoing study of breast cancer survivors which will overcome limitations of prior studies. The proposed study will comprehensively examine clinical and behavioral predictors of CVD outcomes among breast cancer survivors, and will maximize unique patient and data resources available at Kaiser Permanente Northern California (KPNC). We will compare CVD events in the Pathways Study, a cohort of female KPNC members age ≥21 years diagnosed with invasive breast cancer (n=4,453, R01CA105274) with CVD events in a new age, race/ethnicity, history of comorbidity, and length of KPNC membership matched cohort of healthy KPNC female members (n=22,265). Specific aims are: Aim 1) To examine the absolute risk and relative risk of incident CVD events (ischemic heart disease, stroke/transient ischemic attack, and cardiomyopathy/heart failure, and others) and new onset CVD risk factors (hypertension, diabetes, dyslipidemia) in women with breast cancer (Pathways) and a cancer-free comparison group (KPNC matched cohort); Aim 2) In women with a history of breast cancer (Pathways), to examine the relative risk of incident CVD events and new onset of CVD risk factors, by type of cardiotoxic breast cancer treatment received, including chemotherapy/biologic therapy (anthracyclines, trastuzamab), hormonal therapy (Tamoxifen, aromatase inhibitors), and radiation therapy, controlling for confounders related to baseline CVD medication adherence, clinical and behavioral risk factors, medical care and health care system factors, and socioeconomic status (SES); Aim 3) To assess adherence to CVD medications in women with a history of breast cancer (Pathways) using 14 years of follow-up data, and to examine the association of adherence with risk of CVD events controlling for cardiotoxic cancer treatment received, baseline CVD clinical and behavioral risk factors, medical care and health care system factors, and SES. Impact: Results from this study will have important implications for identifying breast cancer subgroups at high risk of CVD and identifying potential targets for intervention, such as medication adherence and control of CVD risk factors.