Decreasing hormonal promotion is key to breast cancer prevention.

An early full-term pregnancy in women is highly protective against breast cancer. This protection can be mimicked by short-term treatment with estradiol plus progesterone in nulliparous rats. We determined the effect of long-term hormonal promotion following the protective short-term estradiol and progesterone treatment that mimics parity protection against mammary tumors. Rats were treated with N-methyl-N-nitrosourea before or after protective hormone treatment. In brief, the animals could be broadly classified into three categories. First, the controls that received no protective hormone treatment, second, the short-term protective hormone treated rats, and third, rats which received the short-term protective hormone treatment plus continuous treatment with estradiol or progesterone or a combination of estradiol and progesterone. Different doses of hormones were used for short-term protective and long-term promotion treatments. The experiments were terminated 9 months post carcinogen treatment. Mammary tumor incidence in all the short-term estradiol- plus progesterone-treated rats was significantly lower compared with controls. Short-term hormone treatment followed by long-term promotion resulted in an increased mammary tumor incidence compared with animals that received only the short-term treatment. Overall, the results demonstrate the importance of the promotional environment in mammary carcinogenesis indicating that the decreased promotional environment could be the reason for protection against mammary carcinogenesis.