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

Phase 0
30 Years
55 Years
Not Enrolling
Breast Cancer

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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.

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.

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

- 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.

Type of Study:


Study Design:

Allocation: Non-Randomized, Endpoint Classification: Safety/Efficacy Study, Intervention Model: Parallel Assignment, Masking: Open Label, Primary Purpose: Treatment

Outcome Measure:

Ki67 expression

Outcome Description:

Ki67 expression by hyperplastic breast lesions

Outcome Time Frame:

about 1 year

Safety Issue:


Principal Investigator

Andrea Manni, MD

Investigator Role:

Principal Investigator

Investigator Affiliation:

Milton S. Hershey Medical Center


United States: Institutional Review Board

Study ID:

PSHCI 12-075



Start Date:

March 2013

Completion Date:

March 2018

Related Keywords:

  • Breast Cancer
  • breast cancer
  • omega-3 fatty acids
  • Breast Neoplasms



Penn State Milton S. Hershey Medical Center Hershey, Pennsylvania  17033