Fat Metabolism Following Chemotherapy in Breast Cancer

Study Overview
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Brief Summary
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Following chemotherapy, breast cancer patients primarily gain fat mass and lose muscle mass. Both depletion of muscle and an increase of fat mass in breast cancer patients are related to short survival, and decreased skeletal muscle mass and function may result in fatigue and inactivity, which contributes to fat mass changes and can be responsible for chemo-toxicity and increased mortality. The purpose of this study is to provide detailed insight in chemotherapy related changes in lipid metabolism and gut digestion and absorption of fat in breast cancer patients compared to matched healthy controls. This will provide required information that is necessary to implement new strategies to develop optimal nutritional regimen in breast cancer patients. The hypothesis is that chemotherapy in breast cancer is related to altered gut function and absorption and to increases in fat synthesis that lead to fat accumulation. In addition, we will examine the effect of cancer, chemotherapy, and gender by comparing fat digestion/absorption and fat metabolism of the breast cancer before and after chemotherapy, to aged matched healthy female and male controls.

Detailed Description
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This research study involves 5 visits for the breast cancer subjects and 3 visits for the healthy controls. The first visit includes the informed consent and a screening and the second and third visit for the study days before chemotherapy and the fourth and fifth visit for the study days after chemotherapy. For the first test day, 2 hours of the subjects time will be for urine and blood sample collection, and to ingest the deuterated water. Subjects are allowed to go home after and eat normally. On the second study day, subjects will arrive early that morning and a DXA scan will be performed first. For the duration of the study, subjects have to lie in the bed (except for bathroom privileges). They can watch tv or bring and use a book/tablet. The research nurse or study staff will be present in the human subject area to assist the subject if necessary. Subjects are not allowed to eat or drink during the second test day, except for the test drink (meal) and water. One IV catheter will be placed in a vein of the arm/hand for blood draws. The hand will be placed in a hot box during blood collection. Another IV catheter will be placed in the contra-lateral forearm for a primed and continuous infusion of 2H5-glycerol. Over the two day time period, a total of 100-120 ml of blood will be obtained over approximately 19 samples. Stable isotopes will be ingested on the first test day, added to the test drinks on the second test day after the second hour, and infused on the second day. On the second test day, subjects will fill out questionnaires and perform muscle function tests. After completion of the study, we will provide the subject with a meal.

Official Title
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The Effect of Chemotherapy on Fat Metabolism and Digestion and Function in Breast Cancer Patients.

Conditions
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Breast Cancer

Participation Criteria
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Eligibility Criteria
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Inclusion criteria cancer subjects: Diagnosed with breast cancer Scheduled for chemotherapy Ability to sign informed consent Age 30 years and older Ability to lie in supine position for 7 hours Inclusion criteria healthy subjects: Healthy male & female according to the investigator's or appointed staff's judgment Age 30 years or older No diagnosis of cancer Exclusion Criteria: Presence of fever within the last 3 days Untreated metabolic diseases including hepatic or renal disorder Presence of acute illness or metabolically unstable chronic illness Use of nutritional supplements within 5 days of first test day Any other condition according to the PI or nurse that would interfere with the study or safety of the patient Failure to give informed consent Possible) pregnancy

Ages Eligible for Study
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Minimum Age: 30 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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Accepts Healthy Volunteers

Study Plan
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How is the study designed?
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Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Breast Cancer Patients<br>Breast cancer patients to be studied before and after chemotherapy | |
| Healthy Female Controls<br>Healthy female controls will be compared to breast cancer patients before and after chemotherapy and to healthy male controls | |
| Healthy Male Controls<br>Healthy male controls will be compared to healthy female controls to determine gender differences | |

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Hepatic triglyceride synthesis | changes in hepatic triglyceride synthesis before and after a meal | Pre meal ingestion and 15, 30, 45, 60, 75, 90, 105, 120, 150, 180, 210, 240, 270, and 300 min post meal ingestion | 
| Hepatic de novo lipogenesis | changes in hepatic de novo lipogenesis before and after a meal | Pre meal ingestion and 15, 30, 45, 60, 75, 90, 105, 120, 150, 180, 210, 240, 270, and 300 min post meal ingestion | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Adipose tissue triglyceride synthesis | changes in adipose tissue triglyceride synthesis before and after a meal | pre and 4 hours post meal | 
| Adipose tissue de novo lipogenesis | changes in adipose tissue de novo lipogenesis before and after a meal | pre and 4 hours post meal | 
| Adipose tissue lipolysis - glycerol rate of appearance | changes in adipose tissue lipolysis before and after a meal. plasma enrichment of glycerol. | Pre meal ingestion and 15, 30, 45, 60, 75, 90, 105, 120, 150, 180, 210, 240, 270, and 300 min post meal ingestion | 
| Fat digestion and absorption | defining fat digestion and absorption after a meal. Enrichment in palmitic acid and tripalmitin fatty acids in plasma | Pre meal ingestion and 15, 30, 45, 60, 75, 90, 105, 120, 150, 180, 210, 240, 270, and 300 min post meal ingestion | 
| Skeletal muscle strength and endurance | Difference in leg strength and fatigue | 1 day | 
| Insulin response to feeding | acute changes from postabsorptive state to postprandial state | pre and up to 5 hours post meal | 
| Body composition | body composition will be determined by dual-energy X-ray absorptiometry and by deuterated water dilution technique. Plasma deuterium enrichments will be determined. | 1 day | 
| Physical activity questionnaire | Outcome of physical activity assessment in breast cancer patients and healthy controls in relation to the fat metabolism | 1 day | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Breast Cancer, Fat metabolism, Fat digestion, physical activity, muscle function