Abstract
Introduction
Estrogen exposure is a known risk factor for breast cancer. Phytoestrogens, plant-derived compounds found in the diet, have a structure similar to estradiol. Observational studies suggest that they are associated with a reduced risk of breast cancer recurrence. The objective of this systematic review is to evaluate, based on data from randomized controlled trials, the effect of phytoestrogens on breast cancer prognosis and hormonal markers.Methods
MEDLINE, EMBASE, CENTRAL, and ClinicalTrials.gov were searched from inception to February 2026, without language restrictions. Randomized controlled trials assessing the effect of phytoestrogens on breast cancer prognosis (recurrence and mortality) or on circulating estrogen concentrations (estradiol and estrone) were included. Risk of bias was assessed using the Cochrane RoB-2 tool. A qualitative synthesis was conducted due to study heterogeneity.Results
Four trials (1698 patients) were included. One trial (1542 patients) reported a non-significant reduction in recurrence risk (Relative risk 0.97; 95% Confidence Interval [CI] 0.75-1.27). No randomized trial evaluated mortality. Three trials (156 patients) reported non-significant decreases in estradiol concentrations. One trial (19 patients) showed a significant reduction in estrone concentration (Mean difference -5.50pmol/L; 95% CI -7.53 to -3.47).Discussion
Overall, the available data from trials remain limited and do not provide sufficient support for a protective effect. However, the trials did not report any increase in recurrence risk (1 trial) or circulating estrogen levels (3 trials), rather they suggested trends toward reduction. These findings should nevertheless be interpreted with caution given the limited number of studies available and their relatively small sample sizes.