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Dietary Energy Restriction and Omega-3 Fatty Acids on Mammary Tissue

Early Phase 1
Withdrawn
Conditions
Breast Cancer
Interventions
Drug: Lovaza
Drug: Placebo
Other: Dietary energy restriction
Registration Number
NCT01784042
Lead Sponsor
Milton S. Hershey Medical Center
Brief Summary

The over-reaching goal of this study is to test the merit of combining dietary energy restriction with omega-3 fatty acids as a safe and effective breast cancer chemoprevention strategy in overweight and obese women at high risk.

Detailed Description

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.

Recruitment & Eligibility

Status
WITHDRAWN
Sex
Female
Target Recruitment
Not specified
Inclusion Criteria
  • Five year predicted breast cancer risk of at least 1.66%.
  • Prior breast biopsy showing atypical ductal or lobular hyperplasia or lobular carcinoma in situ or ductal carcinoma in situ (DCIS).
  • Known breast cancer-1 and -2 mutations.
  • Breast density >50% as assessed by the conventional two-dimensional method.
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Exclusion Criteria
  • Weight loss of 10 pounds in past six months.
  • History of fish allergy.
  • Oral contraceptives or hormone replacement therapy in the past 6 months.
  • Pregnancy or lactation in the last 12 months or planning to become pregnant in the next 12 months.
  • Current smoking.
  • Diagnosis of cancer except basal cell carcinoma of the skin or lobular carcinoma in situ or DCIS.
  • Diagnosis of type 1 or type 2 diabetes based on standard criteria, irrespective of treatment.
  • Recent stroke or cardiovascular event.
  • History of eating disorders documented in medical records.
  • History of major gastrointestinal disease impairing absorption.
  • History of bariatric surgery.
  • Recent, current or planned use of diet drugs as per patient history.
  • Participants must not use flaxseed oil supplements during study participation.
  • Participants must not use Omega-3 preparations while participating on this trial.
  • Participants must not use Tamoxifen or Raloxifene during study participation.
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Study & Design

Study Type
INTERVENTIONAL
Study Design
PARALLEL
Arm && Interventions
GroupInterventionDescription
LovazaLovazaLovaza only
Dietary energy restriction plus LovazaDietary energy restrictionDietary energy restriction plus Lovaza
No dietary energy restriction plus PlaceboPlaceboNo dietary energy restriction plus Placebo
Dietary energy restriction plus placeboPlaceboDietary energy restriction plus placebo
Dietary energy restriction plus placeboDietary energy restrictionDietary energy restriction plus placebo
Dietary energy restriction plus LovazaLovazaDietary energy restriction plus Lovaza
Primary Outcome Measures
NameTimeMethod
Ki67 expressionabout 1 year

Ki67 expression by hyperplastic breast lesions

Secondary Outcome Measures
NameTimeMethod

Trial Locations

Locations (1)

Penn State Milton S. Hershey Medical Center

🇺🇸

Hershey, Pennsylvania, United States

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