Diet Composition, Weight Control, and Breast Carcinogenesis
This study is designed to answer questions about how a dietary pattern either high or low in
dietary carbohydrate and fat availability and fat loss influence metabolic and hormonal
processes that may affect breast cancer recurrence. The investigators hypothesize that in
addition to the anticipated effects of fat loss on circulating levels of bioavailable sex
steroids, that the effects of excess fat on breast cancer prognosis can be attributed to
three interrelated metabolic processes: altered glucose metabolism (IGF-1, IGFBP-3, glycated
proteins), chronic inflammation (C-reactive protein, IL-6, TNF-alpha) and excessive cellular
oxidation (8-hydroxy-2-deoxyguanosine and 8-isoprostane F-2 alpha).
A 6 month intervention study involving 370 post menopausal women who have been treated for
breast cancer is proposed. Randomized women, stratified by resected stage, systemic adjuvant
therapy and body mass index (> 25 and < 35 Kg/m2), will serve as either a non-intervention
control group or will follow a tailored diet-physical activity program designed to create a
weekly negative energy balance equivalent to 3500 kcal. The intervention groups will receive
the same physical activity protocol, but one of two diets that differ in dietary pattern.
The specific aims are: Aim 1. Does a dietary pattern either high or low in available
carbohydrate and fat alter the pattern of change observed in circulating factors involved in
glucose homeostasis, chronic inflammation, cellular oxidation, and steroid hormone
metabolism during progressive loss of body fat? The investigators will also examine how
observed changes in these circulating factors related to changes indicators of breast cancer
recurrence. Aim 2. Do circulating factors associated with glucose homeostasis, chronic
inflammation, and cellular oxidation display the same pattern of change in response to
progressive fat loss as circulating analytes associated with sex steroid metabolism?
Analytes of interest will be measured monthly throughout the study. Aim 3. Does dietary
glycemic load affect the magnitude or rate of fat loss? Plasma adipokines such as leptin and
adiponectin and plasma ghrelin will be measured to provide biological determinants that may
help explain differences in response.
The work proposed in this application should provide quantitative data about the importance
of the magnitude of fat loss on metabolic and hormonal processes involved in cancer
recurrence and provide guidance about effective dietary approaches that maximize weight loss
benefits on breast cancer prognosis.
Allocation: Randomized, Endpoint Classification: Efficacy Study, Intervention Model: Parallel Assignment, Masking: Single Blind (Outcomes Assessor), Primary Purpose: Prevention
C-reactive protein, IL-6, TNF-alpha
Baseline and montlhly for 6 months
Henry J Thompson, PhD
Colorado State University
United States: Federal Government
|Rocky Mountain Cancer Center||Denver, Colorado 80218|