Soy isoflavones decrease fibroglandular breast tissue measured by magnetic resonance imaging in premenopausal women: A 2-year randomized double-blind placebo controlled clinical trial

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

Research output: Contribution to journalArticlepeer-review

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.

Original languageEnglish (US)
Pages (from-to)158-168
Number of pages11
JournalClinical Nutrition ESPEN
Volume52
DOIs
StatePublished - Dec 2022

Keywords

  • Breast cancer prevention
  • Breast density
  • Daidzein
  • Genistein
  • Isoflavones
  • Soy

ASJC Scopus subject areas

  • Endocrinology, Diabetes and Metabolism
  • Nutrition and Dietetics

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