Short-term hormone treatment as a chemopreventive method against mammary cancer initiation in rats

Because previous data had suggested that short-term treatment with pharmacological doses of estradiol and progesterone might be an effective means of preventing mammary cancer initiation, additional experiments were performed to confirm this observation and to determine if lower doses of the hormones would also have chemopreventive activity. Rats treated with the steroids for five weeks and administered the carcinogen (methylnitrosourea) three weeks later were observed for one year for the appearance of mammary cancers. Hormone pretreated rats exhibited a reduction in number of mammary cancers of approximately 90% from rats receiving the steroid vehicle. During the extended observation period, treatment with steroids did not induce gross or histological lesions in any tissues. In a separate experiment, decreasing the dose levels from 20 micrograms estradiol plus 4 mg progesterone to 5 mg estradiol plus 2 mg progesterone did not significantly alter the chemopreventive efficacy of the treatment regimen. Differentiation of the mammary gland to a secretory state with hormones apparently alters the epithelial cells so that, even after involution has occurred, the gland maintains its resistance to a carcinogenic insult.