Skip to main content

Hormonal Prevention of Breast Cancer: Significance of Promotional Environment

  • Chapter
Hormonal Carcinogenesis V

Summary

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 20μg, 100μg, 200μg, or 30 mg of E2 in silastic capsules for 3 weeks. 100μg (17%), 200μg (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 20μg (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 (∼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.

This is a preview of subscription content, log in via an institution to check access.

Access this chapter

Subscribe and save

Springer+ Basic
$34.99 /Month
  • Get 10 units per month
  • Download Article/Chapter or eBook
  • 1 Unit = 1 Article or 1 Chapter
  • Cancel anytime
Subscribe now

Buy Now

Chapter
USD 29.95
Price excludes VAT (USA)
  • Available as PDF
  • Read on any device
  • Instant download
  • Own it forever
eBook
USD 169.00
Price excludes VAT (USA)
  • Available as PDF
  • Read on any device
  • Instant download
  • Own it forever
Softcover Book
USD 219.99
Price excludes VAT (USA)
  • Compact, lightweight edition
  • Dispatched in 3 to 5 business days
  • Free shipping worldwide - see info
Hardcover Book
USD 219.99
Price excludes VAT (USA)
  • Durable hardcover edition
  • Dispatched in 3 to 5 business days
  • Free shipping worldwide - see info

Tax calculation will be finalised at checkout

Purchases are for personal use only

Institutional subscriptions

Preview

Unable to display preview. Download preview PDF.

Unable to display preview. Download preview PDF.

Similar content being viewed by others

References

  1. MacMahon B, Cole P Lin TM, et al. (1970) Age at first birth and breast cancer risk. Bull WHO 43:209–221.

    PubMed  CAS  Google Scholar 

  2. Moon RC (1969) Relationship between previous reproductive history and chemically induced mammary cancer in rats. Int J Cancer 4:312–317.

    Article  PubMed  CAS  Google Scholar 

  3. Marchant J (1955) Influence of pregnancy and lactation on the incidence of mammary carcinoma induced with methylcholanthrene in female mice of the IF strain. J Pathol Bacteriol 70:415–418.

    Article  PubMed  CAS  Google Scholar 

  4. Huggins C, Moon RC, Morii S (1962) Extinction of experimental mammary cancer. I. Estradiol-17beta and progesterone. Proc Natl Acad Sci USA 48:379–386.

    Article  PubMed  CAS  Google Scholar 

  5. Grubbs CJ Juliana MM, Whitaker LM (1988) Short-term hormone treatment as a chemopreventive method against mammary cancer initiation in rats. Anticancer Res 8:113–117.

    PubMed  CAS  Google Scholar 

  6. Russo IH, Koszalka M, Russo J (1990) Effect of human chorionic gonadotropin on mammary gland differentiation and carcinogenesis. Carcinogenesis 11:1849–1855.

    Article  PubMed  CAS  Google Scholar 

  7. Guzman RC, Yang J, Rajkumar L, et al. (1999) Hormonal prevention of breast cancer: mimicking the protective effect of pregnancy. Proc of the Natl Acad Sci USA 96:2520–2525.

    Article  CAS  Google Scholar 

  8. Rajkumar L, Guzman RC, Yang J, et al. (2001) Short-term exposure to pregnancy levels of estrogen prevents mammary carcinogenesis, Proc Natl Acad Sci USA 98:11755–11759.

    Article  PubMed  CAS  Google Scholar 

  9. Yang J, Yoshizawa K, Nandi S, et al. (1999) Protective effects of pregnancy and lactation against N-methyl-N-nitrosourea-induced mammary carcinomas in female Lewis rats. Carcinogenesis 20:623–628.

    Article  PubMed  Google Scholar 

  10. McMahon C, Suthigphongchai T, DiRenso J, et al. (1999) P/CAF associates with cyclin D1 and potentiates it s activation of the estrogen receptor. Proc Natl Acad Sci USA 96:5382–5387.

    Article  PubMed  CAS  Google Scholar 

  11. Korkola J, Wood G, Archer M (1999) Cyclin D1 expression during rat mammary tumor development and its potential role in the resistance of the Copenhagen rat. Breast Cancer Res 1:88–94.

    Article  PubMed  CAS  Google Scholar 

  12. Yatani R, Shiraishi T, Nakakuki K, et al. (1998) Trends in frequency of latent prostate carcinoma in Japan from 1965–1979 to 1982–1986. J Natl Cancer Inst 80:683–687.

    Article  Google Scholar 

Download references

Author information

Authors and Affiliations

Authors

Editor information

Editors and Affiliations

Rights and permissions

Reprints and permissions

Copyright information

© 2008 Springer

About this chapter

Cite this chapter

Lakshmanaswamy, R., Guzman, R.C., Nandi, S. (2008). Hormonal Prevention of Breast Cancer: Significance of Promotional Environment. In: Li, J.J., Li, S.A., Mohla, S., Rochefort, H., Maudelonde, T. (eds) Hormonal Carcinogenesis V. Advances in Experimental Medicine and Biology, vol 617. Springer, New York, NY. https://doi.org/10.1007/978-0-387-69080-3_46

Download citation

Publish with us

Policies and ethics