In vitro genistein (soybean-derived isoflavone/phytoestrogen) has been reported to suppress angiogenesis. We have produced a soybean extract (SE) enriched in phytoestogens which are heat stable. Heat sterilization (hs) of SE destroys soy protease inhibitor activity and increases isoflavone concentrations. This study was performed to determine the effects of SE with and without heat sterilization on tumor growth and metastasis. Sixty female Lewis rats injected s.c. with mammary tumor (MAC-33) were randomized to receive i.p. injection of SE (18 mg), hsSE (18 mg), or saline (control) 5 times per week for 30 days. After 30 days the rats were sacrificed to determine carcass weight, tumor weight, tumor volume, liver weight, hepatic protease activity (HPA), and number and size of lung metastasis. Comparing either SE or hsSE to controls, significant increases were found in tumor weight (g) (109.4±26.3, 114.9±19.7, 86.8±23.2), tumor volume (cm3) (55.6±14.6, 60.1±12.0, 45.5±14.4), and tumor: carcass ratio (0.59, 0.62, 0.47). Data expressed as mean ± SD (SE, hsSE, control, respectively) was analyzed by ANOVA. There was a significant increase in the number of lung metastasis (31%; Kruskal-Wallis test) in the animals receiving hsSE. Additionally, there was a significant decrease in HPA (26.9%) in the animals receiving SE. Soy protease inhibitors are not responsible for the increase in tumor growth and number of lung metastases seen with SE. Our results suggest that a heat stable component of SE, perhaps the isoflavones, promotes tumor growth and lung metastasis in vivo.