title: Reduction in Ki-67 in benign breast tissue of high-risk women with the lignan secoisolariciresinol diglycoside.
abstract: Preclinical and correlative studies suggest reduced breast cancer with higher lignan intake or blood levels. We conducted a pilot study of modulation of risk biomarkers for breast cancer in premenopausal women after administration of the plant lignan secoisolariciresinol given as the diglycoside (SDG). Eligibility criteria included regular menstrual cycles, no oral contraceptives, a >3-fold increase in 5-year risk, and baseline Ki-67 of ≥2% in areas of hyperplasia in breast tissue sampled by random periareolar fine-needle aspiration (RPFNA) during the follicular phase of the menstrual cycle. SDG (50 mg/d) was given for 12 months, followed by repeat RPFNA. The primary end point was change in Ki-67. Secondary end points included change in cytomorphology, mammographic breast density, serum bioavailable estradiol and testosterone insulin-like growth factor-I and IGF-binding protein-3, and plasma lignan levels. Forty-five of 49 eligible women completed the study with excellent compliance (median = 96%) and few serious side effects (4% grade 3). Median plasma enterolactone increased ∼9-fold, and total lignans increased 16-fold. Thirty-six (80%) of the 45 evaluable subjects showed a decrease in Ki-67, from a median of 4% (range, 2-16.8%) to 2% (range, 0-15.2%; P < 0.001, Wilcoxon signed rank test). A decrease from baseline in the proportion of women with atypical cytology (P = 0.035) was also observed. Based on favorable risk biomarker modulation and lack of adverse events, we are initiating a randomized trial of SDG versus placebo in premenopausal women.
authors: Department of Internal Medicine, University of Kansas Medical Center, Kansas City, Kansas 66160-7418, USA. cfabian@kumc.edu
authors: Carol J
authors: CJ
authors: Fabian
authors: Bruce F
authors: BF
authors: Kimler
authors: Carola M
authors: CM
authors: Zalles
authors: Jennifer R
authors: JR
authors: Klemp
authors: Brian K
authors: BK
authors: Petroff
authors: Qamar J
authors: QJ
authors: Khan
authors: Priyanka
authors: P
authors: Sharma
authors: Kenneth D R
authors: KD
authors: Setchell
authors: Xueheng
authors: X
authors: Zhao
authors: Teresa A
authors: TA
authors: Phillips
authors: Trina
authors: T
authors: Metheny
authors: Jennifer R
authors: JR
authors: Hughes
authors: Hung-Wen
authors: HW
authors: Yeh
authors: Karen A
authors: KA
authors: Johnson
mesh_terms: D000328:Adult; D001940:Breast / Q000187:drug effects* / Q000378:metabolism / Q000473:pathology*; D002072:Butylene Glycols / Q000494:pharmacology*; D004797:Enzyme-Linked Immunosorbent Assay; D004958:Estradiol / Q000097:blood; D005260:Female; D006801:Humans; D006965:Hyperplasia / Q000188:drug therapy / Q000378:metabolism / Q000473:pathology; D007150:Immunohistochemistry; D019394:Ki-67 Antigen / Q000096:biosynthesis* / Q000187:drug effects; D017705:Lignans / Q000494:pharmacology*; D008327:Mammography; D008875:Middle Aged; D048789:Phytoestrogens / Q000494:pharmacology*; D010865:Pilot Projects; D017697:Premenopause; D011374:Progesterone / Q000097:blood; D012307:Risk Factors; D013739:Testosterone / Q000097:blood
chemical_list: D002072:Butylene Glycols; D019394:Ki-67 Antigen; D017705:Lignans; D048789:Phytoestrogens; D013739:Testosterone; D011374:Progesterone; D004958:Estradiol; C060283:secoisolariciresinol