Breast Cancer Survivors Cardiovascular Risks: Treatment and Behavioral Influences

乳腺癌幸存者的心血管风险：治疗和行为影响

• 批准号: 9379087
• 负责人: JANICE KIECOLT-GLASER
• 金额: $ 6.15万
• 依托单位: OHIO STATE UNIVERSITY
• 依托单位国家: 美国
• 财政年份: 2014
• 资助国家: 美国
• 起止时间: 2014-05-19 至 2019-04-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/9379087
• 关键词: Accounting; Address; Adjuvant; Adjuvant Chemotherapy; Adverse effects; Aftercare; Anatomy; Aromatase Inhibitors; Atherosclerosis; Blood; Breast Cancer Treatment; Breast Cancer survivor; Breast Cancer therapy; Cancer Survivor; Cardiovascular system; Carotid Arteries; Cell Adhesion Molecules; Chemotherapy-Oncologic Procedure; Coronary heart disease; Cyclophosphamide; Data; Development; Diagnosis; Dose; Doxorubicin; E-Selectin; Face; Fasting; Fatty acid glycerol esters; Intercellular adhesion molecule 1; Laboratories; Lead; Lipids; Lipoproteins; Liver; Measurement; Menopausal Status; Menopause; Mental Depression; Metabolic; Modeling; Morbidity - disease rate; Obesity; Paclitaxel; Pathway interactions; Pharmaceutical Preparations; Physical activity; Quality of life; Recording of previous events; Risk; Risk Factors; Surrogate Markers; Survivors; Syndrome; Tamoxifen; Triglycerides; Vascular Cell Adhesion Molecule-1; Very low density lipoprotein; Weight Gain; Woman; behavior influence; breast cancer survival; cancer therapy; cardiorespiratory fitness; cardiovascular risk factor; chemotherapy; coronary artery calcification; depressive symptoms; design; docetaxel; hormone therapy; improved; intima media; intimal medial thickening; malignant breast neoplasm; mortality; novel; prospective; public health relevance; response; saturated fat; secondary analysis; treatment group; treatment response

DESCRIPTION (provided by applicant): Adjuvant anticancer therapies have enhanced breast cancer survival, but they can also induce important short- and long-term cardiovascular side effects. Preliminary data from our laboratory suggest a novel cardiovascular risk factor not previously documented: chemotherapy-treated breast cancer survivors have an abnormally delayed and persistent rise in triglycerides after a high fat meal compared with survivors who did not receive chemotherapy. Larger and/or more prolonged postprandial triglyceride responses are reliably associated with enhanced cardiovascular risk. Our preliminary data also show that depression substantially augments triglyceride responses to high saturated fat meals. Depression has well-established effects on cardiovascular morbidity and mortality, and these meal-related changes highlight a previously unrecognized depression-sensitive mechanistic pathway. Accordingly, we will assess lipid and atherogenic responses (triglycerides, VLDLs, adhesion molecules) to a typical Westernized high saturated fat meal in stage I-IIIA breast cancer survivors before any adjuvant treatment, and two years after completion of all primary cancer treatment except for longer-term hormonal therapies. We will compare responses of women who do not receive any chemotherapy with women who receive one of the two most common chemotherapy regimens. In addition to primary analyses by treatment group, secondary analyses will use post-treatment cumulative dose information for each chemotherapy drug to examine the effect of specific agents and their dose intensity. Changes in coronary artery calcification scores will provide an anatomic endpoint. Specific Aims: (1) To prospectively evaluate the impact of chemotherapy treatment on postprandial responses to a high saturated fat meal in women diagnosed with breast cancer. (2) To assess relationships between depression and postprandial responses to a high saturated fat meal before and after cancer treatment. (3) To appraise the relative impact of chemotherapy-related changes in menopausal status, cardiorespiratory fitness, and central adiposity as correlates and predictors of postprandial responses. (4) To evaluate treatment-related postprandial responses to a high saturated fat meal as predictors of coronary artery calcification scores. The data from this study would improve our understanding of the enhanced cardiovascular risks associated with both chemotherapy and depression, and would thus lead to new models for assessment and treatment.

描述（由申请人提供）：辅助抗癌疗法具有增强的乳腺癌存活，但它们也可以诱导重要的短期和长期心血管副作用。我们实验室的初步数据表明，与未接受化学疗法的幸存者相比，高脂肪饮食后，甘油三酸酯过高的甘油三酸酯后，接受化学疗法治疗的乳腺癌幸存者的新型心血管危险因素异常延迟和持续增长。较大和/或更长的餐后甘油三酸酯反应与增强的心血管风险可靠地相关。我们的初步数据还表明，抑郁大大增加了甘油三酸酯对高饱和脂肪粉的反应。抑郁症对心血管发病率和死亡率具有良好的影响，这些与进餐有关的变化突出了先前未认识到的抑郁症敏感的机械途径。因此，我们将评估I-IIIA期乳腺癌幸存者在任何辅助治疗之前的典型西式西式高饱和脂肪粉和所有原发性癌症治疗后两年后，对典型的西式西式高饱和脂肪进餐进行评估脂质和动脉粥样硬化反应（甘油三酸酯，VLDL，粘附分子）。我们将比较与接受两种最常见的化疗方案之一的女性接受任何化学疗法的女性的反应。除了按治疗组进行初级分析外，次级分析还将为每种化学疗法药物使用治疗后累积剂量信息来检查特定药物的作用及其剂量强度。冠状动脉钙化评分的变化将提供解剖终点。具体目的：（1）前瞻性评估化学疗法治疗对餐后对早饱和脂肪饮食的后反应的影响。 （2）评估癌症治疗前后对高饱和脂肪粉的抑郁和餐后反应之间的关系。 （3）评估化学疗法相关的更年期状态，心肺适应性和中央肥胖的相对影响是餐后反应的相关性和预测指标。 （4）评估与治疗相关的餐后反应，以作为冠状动脉钙化评分的预测指标。这项研究的数据将提高我们对与化学疗法和抑郁症相关的增强心血管风险的理解，从而导致新的评估和治疗模型。