Various doses of soy isoflavones do not modify mammographic density in postmenopausal women

By Maskarinec et al. J. Nutr. 139: 98, 1-986, 2009

High mammographic densities confer a higher risk to develop breast cancer. Several studies have indicated that dietary and hormonal factors may modify breast density. Discussion exists sometimes if soy isoflavones may protect against breast cancer as a result of their antiestrogenic activity or could be hypothesized to increase risk as a result of their estrogen-like properties. Also, breast density is inversely associated with age and BMI (1). The Osteoporosis Prevention Using Soy (OPUS) study examined the relation between different doses of an isoflavone supplement and mammographic density in a 2-year long clinical trial designed to document the safety, efficacy and optimal dosage of soy isoflavones to prevent bone loss after menopause.

Study design

The OPUS study was a 2-year, follow-up, multicenter, randomized, double-blind, placebocontrolled, and intent-to-treat clinical trial. A group of 406 postmenopausal women in their early years of menopause were enrolled at 3 collaborating sites. Of the participants, 135 women received 80 mg/d of isoflavone therapy, 134 received 120 mg/d of isoflavone therapy, and the remaining 135 received a placebo. To account for potential differences and changes in isoflavone intakes across groups, each woman completed a Food Frequency Questionnaire (FFQ) before and after 12 and 24 months of treatment.

Mammograms were retrieved for participants performed at baseline, after 1 year, and after 2 years. All films were scanned and quantified for total breast area as well as the dense tissue in the breast to determine percent breast density. Statistical analysis was performed to determine the effects of isoflavones on breast density.


The mammographic density analysis included 358 women, 88% of the OPUS study participants, 303 of whom had a complete set of 3 mammograms. At baseline, the groups were similar in age, BMI, and percent density. There were small variations in density per study site. Measures of mammographic density, i.e. the dense area and percent density, decreased significantly over time by approximately 3%, which reflects the normal decline in fibroglandular tissue in the aging breast. There were no statistically significant differences in percent annual decrease in densities between the treatment groups (placebo = 1.4% ± 0.3; 80mg = 1.6% ± 0.3; 120mg = 1.3% ± 0.3; P = 0.85).


The present OPUS study was well designed to examine possible effects of isoflavones: 2-year duration, large sample size (n = 358); low loss to follow-up (10%); and 2 different dosages of isoflavones to study the dose-response. Intake of an isoflavone supplement did not influence mammographic density. Stratification by age and BMI also did not indicate an effect of the treatment for any subgroup of women.

In this trial, isoflavone supplements did not modify breast density in postmenopausal women: breast density decrease was normal throughout the course of the OPUS study. These results show that a longterm intake of soy germ isoflavones in high concentrations do not have a negative influence on breast health.