Evaluation of Ki-67 measured in benign breast tissue acquired from premenopausal women treated with a flaxseed derivative

Abstract

1507 Background: The lignans enterolactone and enterodiol are derived from the action of gut bacteria on ingested secoisolariciresinol diglycoside (SDG) which is commonly found in flaxseed. Enterolactone and enterodiol are thought to impair mammary carcinogenesis via reduction in aromatase activity and the mid-cycle surge of luteinizing hormone. We assessed the modulatory activity of 1 year of SDG on a number of risk biomarkers for breast cancer in a prospective phase II pilot study. We report the effect of SDG on the primary endpoint, proliferation in benign breast tissue as measured by Ki-67 immunocytochemistry, in the first 35 women completing study. Methods: Premenopausal women age 21 to 55 at increased risk for breast cancer underwent a baseline random periareolar fine needle aspiration (RPFNA) between the first and tenth days of their menstrual cycle. Those with RPFNA evidence of hyperplasia and Ki-67 greater than or equal to 2% were invited to participate. Women taking flaxseed or oral contraceptives were ineligible. All women took one Brevail (lignan research) capsule containing 50 mg of SDG daily. Ki-67 staining was performed with DAKO M7240 antibody on hematoxylin counterstained slides and the number of cells staining positive in 500 cells within hyperplastic clusters was counted. Results: Forty-nine women were enrolled on study between February 2006 and June 2008. Of these, four stopped prematurely, 10 women have not completed, and 35 have completed study and undergone follow-up RPFNA. Baseline characteristics of the 35 women completing study are as follows: median age 44 (range 29–50), median baseline 5-year Gail model risk 1.6% (range 0.1%-5.7%), median Ki-67 4.2% (range 2.0%-16.8%). Thirty seven percent had hyperplasia without atypia, and 63% had atypia. At repeat RPFNA, Ki-67 expression was reduced (median value of 2.0%, range 0%-15.2%); with 29 of the 35 women demonstrating a decrease (median relative reduction of 0.70). Conclusions: Based upon reduction in Ki-67 expression in hyperplastic benign breast tissue after 12 months, 50 mg of SDG administered daily as Brevail appears promising as a preventive. Supported in part by grant R21 CA117847 from the National Cancer Institute. No significant financial relationships to disclose.