A full-term pregnancy early in life reduces the risk of breast cancer (BC) in women. Parity protection against mammary carcinogenesis is also observed in rats and mice. Administration of high pregnancy levels of ovarian hormones to nulliparious rats induces protection from N-methyl-N-nitrosourea (MNU)-induced mammary cancers. We have demonstrated that alone or in combination with progesterone (P) are effective in preventing mammary cancer while P alone is not. We have now determined the actual daily amount of E2 required to confer protection against mammary cancer. Rats were injected with MNU at 7 weeks of age. Two weeks later the rats were treated with 10 nanograms, 100 nanograms, or 1 ngram of E2 per day for 3 weeks in mini-osmotic pumps. All the animals also received a 30 milligram P silastic capsule for 3 weeks. Serum levels of E2 immediately after treatments were 6, 30, and 118 pg/ml, respectively. Control rats had a 90% mammary cancer incidence while rats treated with of per day had no mammary cancers, nine months after MNU treatment. Treatments with 10 nanograms or 100 nanograms of E2 per day did not significantly decrease the mammary cancer incidence compared to the controls; they had a cancer incidence of 78% and 65%, respectively. The blood hormone data indicates that treatmen with 1 microgram of E2 per day results in high late pregnancy levels of and this level of is effective in conferring protection against mammary carcinogenesis. This short-term chemoprevention treatment is as effective as full-term pregnancy, ovariectomy or long-term tamoxifen treatment and there is no permanent loss of ovarian function. This treatment can be used as a paradigm for developing strategies for human BC prevention.

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