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生存率，但也可能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，一种新的心血管风险因素以前没有记录：化疗治疗的乳腺癌幸存者有一个异常延迟和持续的高脂肪餐后甘油三酯上升相比，幸存者谁没有接受化疗。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餐的反应。抑郁症对心血管疾病的发病率和死亡率有明确的影响，这些与膳食相关的变化突出了一个以前未被认识到的抑郁症敏感的机制途径。因此，我们将在任何辅助治疗前和完成所有主要癌症治疗（长期激素治疗除外）后两年内，评估I-IIIA期乳腺癌幸存者对典型西式高饱和脂肪餐的脂质和致动脉粥样硬化反应（甘油三酯、VLDL、粘附分子）。我们将比较未接受任何化疗的女性与接受两种最常见化疗方案之一的女性的反应。除按治疗组进行的主要分析外，次要分析将使用每种化疗药物的治疗后累积剂量信息，以检查特定药物及其剂量强度的影响。冠状动脉钙化评分的变化将提供解剖学终点。具体目标：（1）前瞻性评估化疗治疗对诊断为乳腺癌的女性患者对高饱和脂肪餐餐后反应的影响。(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)评价化疗相关变化对绝经状态、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)评价高饱和脂肪餐的治疗相关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与化疗和抑郁症相关的心血管风险增强的理解，从而产生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.