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: 9079440
• 负责人: JANICE KIECOLT-GLASER
• 金额: $ 97.68万
• 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/9079440
• 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; Health; 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; Process; Quality of life; Recording of previous events; Risk; Risk Factors; Staging; Surrogate Markers; Survivors; 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; response; saturated fat; treatment group; treatment response; very low density lipoprotein triglyceride

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）：辅助抗癌疗法可以提高乳腺癌的生存率，但它们也会引起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了一种以前未记录的新型心血管危险因素：与未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餐后甘油三酯异常延迟且持续升高。较大和/或更长时间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，抑郁症会显着增强甘油三酯对高饱和脂肪膳食的反应。抑郁症对心血管发病率和死亡率具有明确的影响，这些与膳食相关的变化凸显了以前未被认识的抑郁症敏感机制途径。因此，我们将在任何辅助治疗前以及完成所有原发性癌症治疗（长期激素治疗除外）两年后，评估 I-IIIA 期乳腺癌幸存者对典型西式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女性与接受两种最常见化疗方案之一的女性的反应。除了治疗组的初步分析外，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）前瞻性评估化疗对诊断为乳腺癌的女性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症与高饱和脂肪餐餐后反应之间的关系。 (3) 评估化疗相关变化对绝经状态、心肺健康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膳食的反应，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，从而产生新的评估和治疗模型。