Effect of Dietary Energy Restriction and Omega-3 Fatty Acids on Mammary Tissue and Systemic Biomarkers of Breast Cancer Risk

Trial Information

Effect of Dietary Energy Restriction and Omega-3 Fatty Acids on Mammary Tissue and Systemic Biomarkers of Breast Cancer Risk

Obesity over the pre- and postmenopausal years is linked to the risk of postmenopausal
breast cancer. Multiple mechanisms are likely to contribute to obesity associated breast
cancer risk. They include increased insulin like growth factor (IGF)-I bioavailability,
oxidative stress, raised leptin to adiponectin ratio, and increased inflammatory cytokines
which are responsible for the creation of a systemic and local hyperestrogenic milieu by
induction of aromatase and may also be responsible for the reduction in antitumor immunity
by stimulation of immunosuppressive cells. While derivative chromosome disulfiram (DER) has
been shown to reverse some of these obesity related phenotypic features, it is not yet
established whether DER reduces breast cancer risk using validated tissue biomarkers
predictive of breast cancer development. N:3FA (3-fatty acids) have been shown to
ameliorate obesity-induced effects on circulating leptin and adiponectin, insulin
resistance, endogenous estrogen production and inflammation. Although preclinical studies
have indicated a protective effect of n:3FA on mammary carcinogenesis, the data in humans
are inconclusive, likely as a result of the lack of controlled clinical trials.
Investigators hypothesize that the combination of DER and n:3FA will reduce breast cancer
risk in an additive/synergistic fashion through their complementary effects on the multiple
inter-related pathways accounting for the obesity associated breast cancer risk.
Investigators propose to conduct a clinical trial study involving overweight and obese women
between the ages of 30 and 55 who are at high risk of breast cancer and are found on random
periareolar fine needle aspiration to have hyperplasia with or without atypia with Ki67 ≥2
if premenopausal and ≥1.5 if postmenopausal. Following stratification according to
menopausal status they will be randomized to one of four experimental groups.