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.
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