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患者的生存率，但它们也可能诱发重要的短期和长期心血管副作用。我们实验室的初步数据提示了一种新的心血管危险因素：与未接受化疗的乳腺癌幸存者相比，接受化疗的乳腺癌幸存者在高脂肪饮食后甘油三酸酯的异常延迟和持续上升。餐后甘油三酯反应增大和/或延长与心血管风险增加可靠相关。我们的初步数据还表明，抑郁症大大增加了甘油三酯对高饱和脂肪食物的反应。抑郁症对心血管疾病发病率和死亡率的影响已经得到证实，这些与饮食相关的变化突出了以前未被认识到的抑郁症敏感机制途径。因此，我们将评估I-IIIA期乳腺癌幸存者在任何辅助治疗前，以及除长期激素治疗外所有原发性癌症治疗完成两年后，对典型西化高饱和脂肪膳食的脂质和动脉粥样硬化反应（甘油三酯、vldl、粘附分子）。我们将比较未接受任何化疗的妇女与接受两种最常见化疗方案之一的妇女的反应。除了按治疗组进行初步分析外，二级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作用及其剂量强度。冠状动脉钙化评分的变化将提供一个解剖学终点。具体目的：(1)前瞻性评价化疗对乳腺癌患者餐后高饱和脂肪餐反应的影响。(2)评估抑郁症与癌症治疗前后高饱和脂肪餐后反应之间的关系。(3)评估化疗相关的绝经状态、心肺健康和中枢性肥胖变化作为餐后反应的相关因素和预测因素的相对影响。(4)评价高饱和脂肪餐后治疗相关的餐后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化疗和抑郁相关的心血管风险增加的理解，从而为评估和治疗提供新的模型。

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.