Clinical trial NCT01276704: Prevention Strategy for Pre-Menopausal Women at High Risk for Development of Breast Cancer
Official title: Flaxseed Lignan as a Prevention Strategy for Pre-Menopausal Women at High Risk for Development of Breast Cancer
Study type: INTERVENTIONAL
Overall status: TERMINATED
Phase: PHASE2
Conditions: Breast Cancer
Lead sponsor: University of Kansas Medical Center
Sponsor class: OTHER
Collaborators: name: Lignan Research Inc.
First posted: 2011-01-13
Enrollment: 180
Sex: FEMALE
Minimum age (years): 21
Maximum age (years): 49
Standard ages: ADULT
Accepts healthy volunteers: yes
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: PREVENTION

Brief 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.

Detailed description: 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.

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.

Primary outcomes:
measure: Change in Percent of Breast Epithelial Cells With Ki-67 Immunocytochemical Expression
timeFrame: 12 months
Secondary outcomes:
measure: Change in Gene Expression
timeFrame: 12 months
measure: Breast Cancer Prevention Trial (BCPT) Symptom Checklist
timeFrame: 12 months
Other outcomes:
Locations:
city: Little Rock
country: United States
facility: University of Arkansas for Medical Sciences
state: Arkansas
city: Chicago
country: United States
facility: Northwestern University Medical Center
state: Illinois
city: Kansas City
country: United States
facility: University of Kansas Medical Center
state: Kansas
city: Boston
country: United States
facility: Dana Farber Cancer Institute
state: Massachusetts
city: Columbus
country: United States
facility: Ohio State Unviersity Medical Center
state: Ohio
city: Oklahoma City
country: United States
facility: University of Oklahoma Health Sciences Center
state: Oklahoma
city: Seattle
country: United States
facility: University of Washington
state: Washington
Study officials:
affiliation: University of Kansas Medical Center
name: Carol Fabian, MD
role: PRINCIPAL_INVESTIGATOR
References:
citation: Fabian CJ, Khan SA, Garber JE, Dooley WC, Yee LD, Klemp JR, Nydegger JL, Powers KR, Kreutzjans AL, Zalles CM, Metheny T, Phillips TA, Hu J, Koestler DC, Chalise P, Yellapu NK, Jernigan C, Petroff BK, Hursting SD, Kimler BF. Randomized Phase IIB Trial of the Lignan Secoisolariciresinol Diglucoside in Premenopausal Women at Increased Risk for Development of Breast Cancer. Cancer Prev Res (Phila). 2020 Jul;13(7):623-634. doi: 10.1158/1940-6207.CAPR-20-0050. Epub 2020 Apr 20.