Hormonal Prevention of Breast Cancer: Significance of Promotional Environment

Abstract

Early full-term pregnancy reduces the risk of mammary cancer in humans. Rats and mice also exhibit this phenomenon of parity protection. Short-term treatment with pregnancy levels of estradiol (E2) is also highly effective in preventing mammary carcinogenesis. Earlier it has been demonstrated that parous rats treated with carcinogen develop latent microscopic mammary tumors that do not progress further to form overt mammary cancers. In the current investigation, we wanted to find out if short-term treatment with pregnancy levels of E2 also prevents mammary carcinogenesis similar to parity. Rats were injected with N-methyl-N-nitrosourea at 7 weeks of age and treated with 20 microg, 100 microg, 200 microg, or 30mg of E2 in silastic capsules for 3 weeks. 100 microg (17%), 200 microg (17%), and 30mg (17%) doses of E2 resulted in levels of E2 equivalent to pregnancy level and were effective in preventing overt mammary cancer incidence compared with control (100%) or 20 microg (73%) E2 treatment, which did not result in pregnancy levels of E2 in the circulation. Although a significant reduction of overt cancers was observed in the pregnancy levels of E2 treated groups, there was no difference in the incidence of latent microscopic mammary cancers between the E2 treated and the controls. Proliferation of latent microscopic mammary cancers was examined using immunohistochemistry for cyclin D1 expression. Proliferation in the latent microscopic mammary cancers of the protected groups was significantly lower (approximately 2.0-3.0-fold) than the latent microscopic mammary cancers in the unprotected groups. These findings indicate that mammary cancer development can be blocked by inhibiting or blocking promotion and progression of carcinogen initiated cells.