Soy Isoflavones Decrease Fibroglandular Breast Tissue Measured by Magnetic Resonance Imaging in Premenopausal Women: A 2-Year Randomized Double-Blind Placebo Controlled Clinical Trial

Authors

Lee-Jane W Lu
Nai-Wei Chen
Donald G Brunder
Fatima Nayeem
Manubai Nagamani
Thomas K Nishino
Karl E Anderson
Tuenchit Khamapirad

Publication Date

12-1-2022

Journal

Clinical Nutrition ESPEN

Abstract

BACKGROUND & AIMS: Populations consuming soy have reduced risk for breast cancer, but the mechanisms are unclear. We tested the hypothesis that soy isoflavones, which have ovarian hormone-like effects, can reduce fibroglandular breast tissue (FGBT, 'breast density'), a strong risk marker for breast cancer.

METHODS: Premenopausal women (age 30-42 years) were randomized to consume isoflavones (136.6 mg as aglycone equivalents, n = 99) or placebo (n = 98) for 5 days per week up to 2 years, and changes in breast composition measured by magnetic resonance imaging at baseline and yearly intervals were compared after square root transformation using linear mixed effects regression models.

RESULTS: By intention-to-treat analyses (n = 194), regression coefficients (β estimates) of the interaction of time and isoflavone treatment were -0.238 (P = 0.06) and -0.258 (P < 0.05) before and after BMI adjustment, respectively for FGBT, 0.620 (P < 0.05) and 0.248 (P = 0.160), respectively for fatty breast tissue (FBT), and -0.155 (P < 0.05) and -0.107 (P < 0.05), respectively for FGBT as percent of total breast (FGBT%). β Estimates for interaction of treatment with serum calcium were -2.705 for FBT, and 0.588 for FGBT% (P < 0.05, before but not after BMI adjustment). BMI (not transformed) was related to the interaction of treatment with time (β = 0.298) or with calcium (β = -1.248) (P < 0.05). Urinary excretion of isoflavones in adherent subjects (n = 135) significantly predicted these changes in breast composition. Based on the modeling results, after an average of 1.2, 2.2 and 3.3 years of supplementation, a mean decrease of FGBT by 5.3, 12.1, and 19.3 cc, respectively, and a mean decrease of FGBT% by 1.37, 2.43, and 3.50%, respectively, were estimated for isoflavone exposure compared to placebo treatment. Subjects with maximum isoflavone excretion were estimated to have 38 cc less FGBT (or ∼3.13% less FGBT%) than subjects without isoflavone excretion. Decrease in FGBT and FGBT% was more precise with daidzein than genistein.

CONCLUSIONS: Soy isoflavones can induce a time- and concentration-dependent decrease in FGBT, a biomarker for breast cancer risk, in premenopausal women, and moderate effects of calcium on BMI and breast fat, suggesting a beneficial effect of soy consumption.

TRIAL REGISTRATION: www.

CLINICALTRIALS: gov identifier: NCT00204490.

TRIAL REGISTRATION: www.

CLINICALTRIALS: gov identifier: NCT00204490.

Keywords

Female, Humans, Adult, Calcium, Isoflavones, Premenopause, Breast Neoplasms, Magnetic Resonance Imaging, soy, isoflavones, daidzein, genistein, breast density, breast cancer prevention

Comments

Data Availability Statement

PMID: 36513449

DOI

10.1016/j.clnesp.2022.10.007

PMID

36513449

PMCID

PMC9825101

PubMedCentral® Posted Date

December 2023

PubMedCentral® Full Text Version

Author MSS

Published Open-Access

yes