Reduction in Ki-67 in benign breast tissue of high-risk women with the lignan secoisolariciresinol diglycoside.
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.
Fabian
Carol J
CJ
Department of Internal Medicine, University of Kansas Medical Center, Kansas City, Kansas 66160-7418, USA. cfabian@kumc.edu
Kimler
Bruce F
BF
Zalles
Carola M
CM
Klemp
Jennifer R
JR
Petroff
Brian K
BK
Khan
Qamar J
QJ
Sharma
Priyanka
P
Setchell
Kenneth D R
KD
Zhao
Xueheng
X
Phillips
Teresa A
TA
Metheny
Trina
T
Hughes
Jennifer R
JR
Yeh
Hung-Wen
HW
Johnson
Karen A
KA
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
D002072:Butylene Glycols; D019394:Ki-67 Antigen; D017705:Lignans; D048789:Phytoestrogens; D013739:Testosterone; D011374:Progesterone; D004958:Estradiol; C060283:secoisolariciresinol