Short-term exposure to pregnancy levels of estrogen prevents mammary carcinogenesis

It is well established that pregnancy early in life reduces the risk of bre ast cancer in women and that this effect is universal. This phenomenon of p arity protection against mammary cancer is also observed in rodents. Earlie r studies have demonstrated that shortterm administration of estradiol (E) in combination with progesterone mimics the protective effect of parity in rats. In this study, the lowest effective E dosage for preventing mammary c ancer was determined. Rats were injected with N-methyl-N-nitrosourea at 7 w eeks of age; 2 weeks later, the rats were subjected to sustained treatment with 20 mug, 100 mug, 200 mug, or 30 mg of E in silastic capsules for 3 wee ks. Treatments with 100 mug, 200 mug, and 30 mg of E resulted in serum leve ls of E equivalent to those of pregnancy and were highly effective in preve nting mammary cancer. E treatment (20 mug) did not result in pregnancy leve ls of E and was not effective in reducing the mammary cancer incidence. In another set of experiments, we determined the effect of different durations of E with or without progesterone treatments on mammary carcinogenesis. Th ese experiments indicate that a period as short as one-third the period of gestation is sufficient to induce protection against mammary carcinogenesis . The pioneering aspect of our study in contrast to long-term estrogen expo sure, which is thought to increase the risk of breast cancer, is that short -term sustained treatments with pregnancy levels of E can induce protection against frank mammary cancer.