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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.
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.
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| Label | Type | Description | Intervention Names |
|---|---|---|---|
| Breast Cancer Patients | Breast cancer patients to be studied before and after chemotherapy | ||
| Healthy Female Controls | Healthy female controls will be compared to breast cancer patients before and after chemotherapy and to healthy male controls | ||
| Healthy Male Controls | Healthy male controls will be compared to healthy female controls to determine gender differences |
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| 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 |
| 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 |
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Inclusion criteria cancer subjects:
Inclusion criteria healthy subjects:
Exclusion Criteria:
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Subjects with breast cancer will be recruited when visiting a medical or cancer clinic in and outside the surrounding area of College Station. Cancer patients and healthy subjects will also be recruited by responding to distributed flyers in the community in the College Station area; for example in hospital/clinic waiting areas, clinic rooms and bulletin boards at Scott & White and the CSMC or any other hospital. Other general recruitment material in relation to the nutrition research that the research group performs at Texas A&M can be placed on bulletin boards at Scott & White and the CSMC.
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| Name | Affiliation | Role |
|---|---|---|
| Marielle Engelen, Ph.D. | Texas A&M University | Principal Investigator |
| Facility | Status | City | State | ZIP | Country | Contacts |
|---|---|---|---|---|---|---|
| Texas A&M University | College Station | Texas | 77843 | United States |
| PubMed Identifier | Type | Citation | Retractions |
|---|---|---|---|
| 42149813 | Derived | Huttl VN, Deutz N, Wierzchowska-McNew RA, Ruebush LE, Engelen M. Whole-body and intracellular arginine metabolism in hypertension: role of disease severity and sex. Am J Hypertens. 2026 May 18:hpag047. doi: 10.1093/ajh/hpag047. Online ahead of print. |
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| ID | Term |
|---|---|
| D001943 | Breast Neoplasms |
| D009043 | Motor Activity |
| ID | Term |
|---|---|
| D009371 | Neoplasms by Site |
| D009369 | Neoplasms |
| D001941 | Breast Diseases |
| D012871 | Skin Diseases |
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Urine, adipose tissue, serum, plasma
| 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 |
| D017437 |
| Skin and Connective Tissue Diseases |
| D001519 | Behavior |