Results of three life-span experimental carcinogenicity and anticarcinogenicity studies on tamoxifen in rats.

Tamoxifen was submitted to carcinogenicity bioassays on Sprague-Dawley rats (of the colony used at the Cancer Research Center in the Castle of Bentivoglio of the European Ramazzini Foundation of Oncology and Environmental Sciences) at the dose of 3.3 mg/kg b.w., by stomach tube, in three experiments. In the first experiment the drug was administered once daily, 6 days a week to male and female rats, 8 weeks old at start for their life span. In the second experiment, the drug was administered to female rats, 12 weeks old at start, once daily for 8 consecutive days every 8 weeks for their life span. In the third experiment the drug was administered to female rats, 56 weeks old at start, 6 times weekly for 40 weeks; and then the animals were kept alive for their life span. In the first experiment, a mild increase in hepatocarcinomas with low grading was detected. In the first and second experiments, a borderline increase in uterine malignancies was found. No carcinogenic effect was observed in the third experiment. In the three experiments, tamoxifen showed a strong, long-lasting chemopreventive effect on mammary benign tumors and cancers. The presented data also indicate that tamoxifen treatment reduces the incidence of other tumors: pituitary adenomas, adrenal pheochromocytomas, islet cell pancreatic tumors, Leydig cell testicular tumors, and polyps of the uterus.