Breast Cancer Risk Biomarkers in Premenopausal 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: 36.0
Sex: Female
Minimum age: 25 Years
Maximum age: 54 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 premenopausal and between the ages of 25 and 54 and must have had a
             menstrual period within the past 12 months. Women who are not menstruating regularly
             due to use of certain types of contraceptives may be entered with restrictions. Their
             estrogen progesterone, and follicle stimulating hormone (FSH) levels must be
             documented at baseline random periareolar fine needle aspiration (RPFNA) and their off
             study RPFNA must take place at a similar portion of their cycle (high or low
             progesterone levels). In order to do this a serum progesterone will have to be
             obtained ~ 4 weeks before planned RPFNA and again 2 weeks later such that the RPFNA
             can be performed in the same phase of the "cycle" as baseline.

          -  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 three times the average risk for a woman of the
             same age using either the Surveillance Epidemiology and End Results (SEER,
             http://seer.cancer.gov) database or the NCI Breast Cancer Risk Assessment Tool
             (www.cancer.gov/bcrisktool)., or 10 yr Tyrer-Cuzick risk twice that of the population
             risk as listed in model, or RPFNA atypia

          -  BMI <40 Kg/m3

          -  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).

          -  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. If not using an oral, vaginal, or topical contraceptive, must be
             willing to actively use barrier methods of contraception to prevent pregnancy.

          -  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 must be willing to undergo measurement of height, weight, and BMI and undergo
             body composite analysis (DEXA) at initiation and conclusion of intervention.

          -  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
             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 contralateral
             (uninvolved breast) will be studied by RPFNA. The subject may not have had any
             radiation therapy to the contralateral breast to be studied

          -  Subjects > 40 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. Subjects of sufficient age and/or risk for a baseline mammogram
             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 14 or higher). There must be ≥500 epithelial
             cells on the slide for cytomorphology and evidence of proliferation by Ki-67 staining.
             There must be sufficient reserved methanol- formalin-fixed material for real time
             quantitative 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. Baseline urine sample will in part be used to document that subject is not
             pregnant.

          -  Subjects must be willing to complete questionnaires regarding diet and supplement use,
             quality of life, 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 this
             includes pregnancy, lactation, or stopping or starting hormonal contraceptives..

          -  Women who have taken omega 3 fatty acid supplements within 3 weeks prior to their
             baseline RPFNA.

          -  Women who regularly take NSAIDS (>7 tablets weekly).

        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.