accrual rate lower than anticipated; funding expired

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

The investigators would like to see if women at increased risk for breast cancer are likely to tolerate SDG daily for 12 months without significant side effects or changes in their menstrual cycles. The investigators would also like to determine if Brevail® can reduce breast cell proliferation in pre-menopausal women.

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.

Global results will be published.

12 months

When individual (non-serious) adverse events are diverse, with small numbers in any one event type, total numbers of participants reporting the most severe AE grade are reported.

Early termination led to small numbers of subjects analyzed. A total of 240 enrollees was planned; actual accrual was 180.