Short-Term Exposure to Pregnancy Levels of Estrogen Prevents Mammary Carcinogenesis

• Published in: Proceedings of the National Academy of Sciences - PNAS Vol. 98; no. 20; pp. 11755 - 11759
• Main Authors: Rajkumar, Lakshmanaswamy, Guzman, Raphael C., Yang, Jason, Thordarson, Gudmundur, Talamantes, Frank, Nandi, Satyabrata
• Format: Journal Article
• Language: English
• Published: United States National Academy of Sciences 25.09.2001; National Acad Sciences; The National Academy of Sciences
• Subjects: Alkylating Agents - administration & dosage; Alkylating Agents - pharmacology; Animals; Biological Sciences; Breast cancer; Cancer incidence; Capsules; Carcinogenesis; Carcinogens; Dosage; Dose-Response Relationship, Drug; Estradiol - blood; Estradiol - pharmacology; Estrogens; Female; Health risk assessment; Hormones; Mammary glands; Mammary Glands, Animal - cytology; Mammary Glands, Animal - drug effects; Mammary Neoplasms, Experimental - pathology; Mammary Neoplasms, Experimental - prevention & control; Methylnitrosourea - administration & dosage; Methylnitrosourea - pharmacology; Pregnancy; Prevention; Rats; Rats, Inbred Lew; Silicone Elastomers - pharmacology; Studies; Time Factors
• ISSN: 0027-8424; 1091-6490
• DOI: 10.1073/pnas.201393798

It is well established that pregnancy early in life reduces the risk of breast cancer in women and that this effect is universal. This phenomenon of parity protection against mammary cancer is also observed in rodents. Earlier studies have demonstrated that short-term 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 cancer was determined. Rats were injected with N-methyl-N-nitrosourea at 7 weeks of age; 2 weeks later, the rats were subjected to sustained treatment with 20 µg, 100 µg, 200 µg, or 30 mg of E in silastic capsules for 3 weeks. Treatments with 100 µg, 200 µg, and 30 mg of E resulted in serum levels of E equivalent to those of pregnancy and were highly effective in preventing mammary cancer. E treatment (20 µg) did not result in pregnancy levels 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. These 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 exposure, 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.