Breast Cancer Risk Biomarkers in Postmenopausal Women
Condition: Breast Cancer
MeSH terms: Breast Neoplasms
Intervention: Lovaza™
Intervention description: 4 capsules daily for 6 months
Phase: Phase 2
Study type: Interventional
Primary purpose: Prevention
Intervention model: Single Group Assignment
Masking: None (Open Label)
Enrollment: 35.0
Sex: Female
Minimum age: 25 Years
Maximum age: 70 Years
Healthy volunteers: Accepts Healthy Volunteers

Summary:

      This study is designed to gather information on how the prescription drug Lovaza™ which
      contains omega-3 fatty acids, affects blood and tissue risk biomarkers for breast cancer.
      This drug is currently approved by the FDA for reducing blood levels of triglycerides.
    

Eligibility criteria:

        Inclusion Criteria

          -  Subjects must be postmenopausal and between the ages of 25 and 69 years. Menopause is
             defined by no menstrual period for more than one year and intact uterus and ovaries,
             or women with intact ovaries but without a uterus and age 50 and over, or a woman with
             both estradiol and follicle stimulating hormone (FSH) in the postmenopausal range or
             any woman who has had her ovaries removed.

          -  Subjects must be at increased risk for breast cancer on the basis of at least one of
             the following criteria:

               -  A five-year Gail risk of ≥ 1.67% or ≥ 2X the average risk for a woman of the same
                  age using either the Surveillance Epidemiology and End Results (SEER,
                  http://seer.cancer.gov) database, the NCI Breast Cancer Risk Assessment Tool
                  (www.cancer.gov/bcrisktool), or the International Breast Cancer Intervention
                  Study (IBIS) Risk Evaluator (http://www.emstrials.

        org/riskevaluator/), or a ten-year Tyrer-Cuzick model risk of 2x that of the population
        risk.

          -  A first degree relative with breast cancer under the age of 60 or multiple second
             degree relatives with breast cancer.

          -  Multiple prior biopsies or at least one prior biopsy exhibiting atypical hyperplasia
             (AH), lobular carcinoma in situ (LCIS), ductal carcinoma in situ (DCIS).

          -  Random periareolar fine needle aspiration (RPFNA) evidence of hyperplasia with atypia
             within the last three years;

          -  Chest or neck radiation before age 30;

          -  Mammographic breast density by visual estimate equals or exceeds 50%.

               -  Subjects must be willing to continue the same hormonal milieu present at baseline
                  throughout trial (Cannot start or stop any type of hormone replacement therapy
                  with the exception of vagifem or estring).

               -  Six months or more must have elapsed from completion of a prevention intervention
                  trial (with exception of a weight reduction trial), ingestion of a selective
                  estrogen receptor modulator (SERM) or aromatase inhibitor (AI) prior to baseline
                  biomarker assessment. .

               -  Subjects with a history of AH, LCIS, or ER-positive DCIS by diagnostic biopsy,
                  must have been counseled about appropriate standard prevention therapies such as
                  tamoxifen or raloxifene and are either not eligible or are not interested in
                  standard prevention therapies. Women with DCIS must have had appropriate local
                  therapy (lumpectomy plus radiation or mastectomy). If subject has had a DCIS, at
                  least two months must have elapsed from surgery and/or radiation therapy to the
                  involved breast. Only the contra-lateral (uninvolved breast) will be studied by
                  RPFNA. The subject may not have had any radiation therapy to the contra-lateral
                  breast to be studied

               -  Subjects must have had a screening mammogram within 6 months of entering the
                  interventional portion of the study and read as not suspicious for breast cancer
                  or if suspicious must have completed all suggested tests including biopsy and
                  found to have no evidence of cancer. Women must be willing to have an off-study
                  mammogram performed 6 months after study entry.

               -  Subjects must have had an RPFNA of the breast within six months prior to entering
                  the intervention portion of the study and be willing to have another RPFNA at
                  ~6.5 months after starting Lovaza™.

               -  Tissue Eligibility: Subjects must have cytomorphologic evidence of hyperplasia
                  with atypia or borderline atypia (Masood score > 13). There must be ≥500
                  epithelial cells on the slide for cytomorphology. There must be sufficient
                  reserved methanol-formalin- fixed material for quantitative reverse transcription
                  polymerase chain reaction (RT-qPCR). Frozen tissue must also have been obtained
                  for fatty acid analysis, reverse phase proteomics, adipokines and cytokines, and
                  RT-qPCR.

               -  Subjects must be willing to undergo phlebotomy at baseline and 6 months and 6.5
                  months. Approximately 3 tablespoons of blood will be obtained at baseline and 6
                  months and 6.5 months or 6 tablespoons if the subject decides to participate in
                  the optional monocyte cytokine release assay .

               -  Subjects must produce a spot urine sample at baseline, 6 months, and at study
                  conclusion

               -  Subjects must be willing to undergo measurement of height, weight, and BMI and
                  undergo body composite analysis (DEXA) at initiation and conclusion of
                  intervention.

               -  Subjects must be willing to complete questionnaires regarding diet and supplement
                  use, quality of life as well as relevant family history personal health and
                  reproductive history and medications at initiation and conclusion of the
                  intervention. Subjects must be willing to sign an informed consent for the entire
                  study and separate consent for repeat RPFNA.

        Exclusion Criteria

          -  Women that have had a metastatic malignancy of any kind.

          -  Women that have had prior invasive breast cancer, diagnosed or treated within the past
             five years.

          -  Women who are currently taking anticoagulants.

          -  Women who have breast implants.

          -  Women who have undergone change in their hormonal milieu in the past 6 months.

          -  Women who have taken omega 3 fatty acid or flaxseed supplements within 3 weeks prior
             to their baseline RPFNA or women who have taken high dose omega 3 within the past
             three months.

          -  Women who regularly take NSAIDS (>7 tablets weekly).

          -  Women who have taken a SERM, aromatase inhibitor or participated in a chemoprevention
             or other investigational drug study within six months prior to baseline RPFNA.

          -  Women who have abnormal renal or hepatic function at baseline, defined as blood
             chemistry values clinically significantly outside of normal institutional ranges.

          -  Women who have a history of an allergy, including hives, to fish products.

          -  Women who have a BMI of 40 kg/m^2 or greater.

        Inclusion of Women and Minorities This study utilizes women at increased risk for breast
        cancer. Subjects recruited from an established cohort of women followed in the Breast
        Cancer Prevention Center. From previous trials we can expect 6% minority accrual which is
        similar to our hospital demographics. Males are not included due to the low absolute risk
        of breast cancer, and the difficulty of performing RPFNA on the male breast.