(R)-Equol is an agonist of both ERα and ERβ with K_is of 27.4 and 15.4 nM, respectively. IC50 & Target: Ki: 27.4 nM (ERα), 15.4 nM (ERβ)^[1] In Vitro: (R)-Equol is an agonist of both ERα and ERβ with K_is of 27.4 and 15.4 nM, respectively^[1]. (R)-Equol induces a dose-dependent inhibitory effect on the invasive capacity of MDA-MB-231 cells that is significant at the highest concentration tested (50 μM). Following 48-h exposure to (R)-Equol, invasion is reduced by 62% (p=0.009, versus untreated cells) with 50 μM (R)-Equol. Matrix metalloproteinase-2 (MMP-2) expression is significantly down-regulated following treatment with 50 μM (R)-Equol (p=0.035)^[2]. In Vivo: Animals fed (R)-Equol have a significantly reduced number of palpable tumors over time when compare with Controls (P=0.002). Furthermore, the number of palpable tumors formed per rat in the (R)-Equol-fed group is significantly lower than that of rats treated with S-(-)equol (P=0.008). (R)-Equol-fed animals have 43% fewer tumors than the control group and this difference is highly statistically significant (P=0.004). The number of tumors/tumor-bearing animal is significantly lower in the animals fed (R)-Equol compare with Controls (3.3±0.4 versus 5.5±0.5, P=0.004). At necropsy, the mean (±SEM) tumor weight per animal for (R)-Equol fed rats (5.3±1.1 mg) is significantly reduced (P=0.04) when compare with Controls (9.9±1.4 mg). Feeding the (R)-Equol diet results in significantly increased tumor latency (P=0.003)^[3].