Breast Cancer Survivors Cardiovascular Risks: Treatment and Behavioral Influences

描述(由申请人提供)：辅助抗癌治疗提高了乳腺癌的存活率，但它们也会引起重要的短期和长期心血管副作用。来自我们实验室的初步数据表明，一个以前没有文献记载的新的心血管危险因素：与没有接受化疗的幸存者相比，接受化疗的乳腺癌幸存者在高脂肪饮食后甘油三酯的异常延迟和持续上升。更大和/或更长的餐后甘油三酯反应与心血管风险增加可靠地相关。我们的初步数据还显示，抑郁症大大增强了甘油三酯对高饱和脂肪饮食的反应。抑郁症对心血管发病率和死亡率有公认的影响，这些与膳食相关的变化突显了一种以前未知的抑郁症敏感机制。因此，我们将评估I-IIIA期乳腺癌患者在接受任何辅助治疗之前以及除长期激素治疗外的所有主要癌症治疗完成两年后，对典型西化高饱和脂肪餐的血脂和动脉粥样硬化(甘油三酯、低密度脂蛋白、黏附分子)的反应。我们将比较没有接受任何化疗的女性和接受两种最常见化疗方案之一的女性的反应。除了按治疗组进行的初步分析外，二次分析将使用每种化疗药物的治疗后累积剂量信息来检查特定药物的效果及其剂量强度。冠状动脉钙化积分的变化将提供一个解剖终点。具体目的：(1)前瞻性评估化疗对诊断为乳腺癌的女性患者高饱和脂肪餐后反应的影响。(2)评估癌症治疗前后抑郁与高饱和脂肪餐餐后反应之间的关系。(3)评价化疗对绝经状态、心肺功能和中心性肥胖的相对影响，作为餐后反应的相关因素和预测因素。(4)评估与治疗相关的餐后对高饱和脂肪饮食的反应，作为冠状动脉钙化评分的预测因子。这项研究的数据将提高我们对与化疗和抑郁症相关的心血管风险增加的理解，从而将导致新的评估和治疗模型。

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.