Prevention Strategy for Pre-Menopausal Women at High Risk for Development of Breast Cancer
Condition: Breast Cancer
MeSH terms: Breast Neoplasms
Intervention: Placebo; secoisolariciresinol
Intervention description: The placebo contains same filler materials as commercially available Brevail® but without active SDG.; 1 capsule daily of secoisolariciresinol diglycoside (SDG)50mg
Intervention MeSH terms: Secoisolariciresinol
Phase: Phase 2
Study type: Interventional
Primary purpose: Prevention
Allocation: Randomized
Intervention model: Parallel Assignment
Masking: Double (Participant, Investigator)
Enrollment: 180.0
Sex: Female
Minimum age: 21 Years
Maximum age: 49 Years
Healthy volunteers: Accepts Healthy Volunteers

Summary:

      The investigators will study the effect of 12 months of SDG (Brevail) vs placebo on women at
      increased risk for development of breast cancer.
    

Eligibility criteria:

        PARTICIPANT SELECTION

          -  Risk Level Required for RPFNA Screening for Eligibility

               -  Given the low probability of side effects and the desire to be able to generalize
                  results to a moderate as well as high risk population, the target cohort is
                  pre-menopausal women who have a relative risk for breast cancer which is 2-fold
                  or greater than that of the average woman in their age group by virtue of any one
                  of the following conditions:

          -  A 1st or 2nd degree relative with breast cancer diagnosed under the age of 60

          -  A prior biopsy indicating proliferative breast disease, atypical hyperplasia, or LCIS

          -  Multiple prior breast biopsies regardless of histology

          -  50% or higher estimated mammographic density on visual inspection

          -  Prior or current RPFNA evidence of atypia

          -  Known carrier of a BRCA1 or 2 mutation.

               -  Age, Life-Style and Medical Eligibility Criteria for Tissue Screening

        Candidates for tissue screening for this study are pre-menopausal women who meet the risk
        criteria above and all of the following demographic and medical criteria:

          -  Age 21 to 49 (limiting the maximum age to 49 will reduce the possibility of reduction
             in Ki-67 due to entry into menopause transition during the study).

          -  Stable hormonal status for the previous 6 months (has not stopped or started oral
             contraceptives, or experienced lactation or pregnancy) and willing to maintain same
             status while on study.

          -  BMI < 40 kg/m2.

          -  Has had at least 4 menstrual cycles in past year

          -  If regularly undergoing screening mammography, must have been performed within 9
             months prior to baseline RPFNA, and interpreted as not suspicious for breast cancer

          -  Breast exam interpreted as normal (not suspicious for cancer).

               -  Exclusion Criteria for Screening RPFNA and Study Participation

        Candidates are ineligible for tissue screening if they meet any of the following
        conditions:

          -  Consumption of systemic antibiotics during the 3 weeks prior to baseline RPFNA.
             Systemic antibiotics reduce intestinal bacteria and thus the ability to convert SECO
             to ENL.

          -  Consumption of supplements containing SDG (flaxseed or sesame seed) during the 3 weeks
             prior to baseline RPFNA. ( Consumption of foods containing flaxseed or sesame seed are
             OK.)

          -  Use of any selective estrogen receptor modulator or aromatase inhibitor (tamoxifen,
             raloxifene, arzoxifene, acolbifene, anastrozole, exemestane, letrozole) within the
             previous 6 months.

          -  Currently enrolled on an interventional investigational study.

          -  Bilateral breast implants.

          -  Invasive breast cancer or other invasive cancer diagnosis within five years.

          -  Metastatic malignancy of any kind.excluding Hodgkin's or non-Hodgkin's lymphoma.

          -  Current anticoagulant use.

          -  Consumption of coumadin, fish oil, or other anticoagulants during the 3 weeks prior to
             baseline RPFNA.

          -  Any other condition or intercurrent illness that in the opinion of the investigator
             makes the subject a poor candidate for RPFNA or the trial.

               -  Inclusion Criteria for Study Entry

          -  RPFNA performed in the follicular portion (day 1-10) of the menstrual cycle. Note that
             day 1 is defined as the first day of bleeding.

          -  RPFNA specimen exhibits hyperplasia +/- atypia (Masood score of ≥13) with ≥500 cells
             on the cytology slide.

          -  Ki-67 ≥2% positivity (≥500 cells).

          -  Willing to continue without oral contraceptives throughout the duration of the study
             participation (12 months). Non-oral contraceptives are permissible. If heterosexually
             active, must be agreeable to use some non-hormonal form of contraception during the
             trial or husband or partner must have had a vasectomy. (Safety of SDG during pregnancy
             has not been documented).

          -  Have reasonable organ function as documented by metabolic chemistry profile.

          -  Willing to undergo a history and physical at baseline and 12 months and be contacted
             periodically by the trial coordinator during the 12 month study period.

          -  Willing to have blood drawn at baseline and twelve months.

          -  Able to understand and willing to provide informed consent for the RPFNA's and study
             participation.