Breast Development, Hormones and Cancer

Part of the Advances in Experimental Medicine and Biology book series (AEMB, volume 630)


Breast cancer originates in undifferentiated terminal structures of the mammary gland. The terminal ducts of the Lob 1 of the human female breast, which are the sites of origin of ductal carcinomas, are at their peak of cell replication during early adulthood, a period during which the breast is more susceptible to carcinogenesis. The susceptibility of Lob 1 to undergo neoplastic transformation has been confirmed by in vitro studies, which have shown that this structure has the highest proliferative activity, estrogen receptor content and rate of carcinogen binding to the DNA. The higher incidence of breast cancer observed in nulliparous women supports this concept, whereas the protection afforded by early full-term pregnancy in women could be explained by the higher degree of differentiation of the mammary gland at the time in which an etiologic agent or agents act.


Breast Cancer Estrogen Receptor Mammary Gland Nulliparous Woman Parous Woman 


Unable to display preview. Download preview PDF.

Unable to display preview. Download preview PDF.


  1. 1.
    Russo J, Gusterson BA, Rogers AE et al Comparative study of human and rat mammary tumorigenesis. Lab Invest 1991; 62:1–32.Google Scholar
  2. 2.
    Wellings SR. Development of human breast cancer. Adv Cancer Res 1980; 31:287–99.CrossRefPubMedGoogle Scholar
  3. 3.
    Wellings SR, Jensen HM, Marcum RG. An atlas of subgross pathology of 16 human breasts with special reference to possible precancerous lesions. J Natl Cancer Inst 1975; 55:231–75.PubMedGoogle Scholar
  4. 4.
    Russo J, Rivera R, Russo IH. Influence of age and parity on the development of the human breast. Breast Cancer Res Treat 1992; 23:211–8.CrossRefPubMedGoogle Scholar
  5. 5.
    Russo J, Romero AL, Russo IH. Architectural pattern of the normal and cancerous breast under the influence of parity. J Cancer Epidemiol Biomarkers_& Prevention 1994; 3:219–24.Google Scholar
  6. 6.
    Russo J, Russo IH. Role of differentiation in the pathogenesis and prevention of breast cancer. Endocr Related Cancer 1997; 4:7–21.CrossRefGoogle Scholar
  7. 7.
    Russo J, Ao X, Grill C et al. Pattern of distribution for estrogen receptor α and progesterone receptor in relation to proliferating cells in the mammary gland. Breast Cancer Res Treat 1999; 53:217–27.CrossRefPubMedGoogle Scholar
  8. 8.
    Clarke RB, Howell A, Anderson E. Estrogen sensitivity of normal human breast tissue in vivo and implanted into athymic nude mice: analysis of the relationship between estrogen-induced proliferation and progesterone receptor expression. Breast Cancer Res Treat 1997; 45:121–83.CrossRefPubMedGoogle Scholar
  9. 9.
    Russo J, Calaf G, Russo IH. A critical approach to the malignant transformation of human breast epithelial cells. CRC Crit Rev Oncol 1993; 4:403–17.Google Scholar
  10. 10.
    Russo J, Reina D, Frederick J et al. Expression of phenotypical changes by human breast epithelial cells treated with carcinogens in vitro. Cancer Res 1988; 48:2837–57.PubMedGoogle Scholar
  11. 11.
    Foster JS, Wimalasena J. Estrogen regulates activity of cyclin-dependent kinases and retinoblastoma protein phosphorylation in breast cancer cells. Mol Endocrinol 1996; 10:488–98.CrossRefPubMedGoogle Scholar
  12. 12.
    Wang W, Smith R, Burghardt R et al. 17β estradiol-mediated growth inhibition of MDA-MB 468 cells stably transfected with the estrogen receptor: cell cycle effects. Mol Cell Endocrinol 1997; 133:49–62.CrossRefPubMedGoogle Scholar
  13. 13.
    Levenson AS, Jordan VC. Transfection of human estrogen receptor (ER) cDNA into ER negative mammalian cell lines. J Steroid Biochem Mol Biol 1994; 51:229–39.CrossRefPubMedGoogle Scholar
  14. 14.
    Weisz A, Bresciani F. Estrogen regulation of proto-oncogenes coding for nuclear proteins. CRC Crit Rev Oncol 1993; 4:361–88.Google Scholar
  15. 15.
    Zajchowski DA, Sager K, Webster L. Estrogen inhibits the growth of estrogen receptor negative, but not estrogen receptor positive, human mammary epithelial cells expressing a recombinant estrogen receptor. Cancer Res 1993; 53:5004–11.PubMedGoogle Scholar
  16. 16.
    Pilat MJ, Christman JK, Brooks SC. Characterization of the estrogen receptor transfected MCF-10A breast cell line 139B6. Breast Cancer Res Treat 1996; 37:253–66.CrossRefPubMedGoogle Scholar
  17. 17.
    Calaf G, Tahin Q, Alvarado ME et al. Hormone receptors and cathepsin D levels in human breast epithelial cells transformed by chemical carcinogens. Breast Cancer Res Treat 1993; 29:169–77.CrossRefGoogle Scholar
  18. 18.
    Russo J, Lareef MH, Balogh G et al. Estrogen and its metabolites are carcinogenic in human breast epithelial cells. J Steroid Biochem Mol Biol 2003; 87:1–25.CrossRefPubMedGoogle Scholar
  19. 19.
    Fernandez SV, Lareef MH, Russo IH et al. Estrogen and its metabolite 4-hydroxy-estradiol induce mutations in TP53 and LOH in chromosome 13q12.3 near BRCA2 in human breast epithelial cells. Int J Cancer 2006; 118:1862–8.CrossRefPubMedGoogle Scholar
  20. 20.
    Russo J, Fernandez SV, Russo PA et al. 17-beta estradiol induces transformation and tumorigenesis in human breast epithelial cells. FASEB J 2006; 20:1622–34.CrossRefPubMedGoogle Scholar
  21. 21.
    Russo J, Russo IH. Development of Human Mammary Gland. In: The Mammary Gland Development, Regulation and Function. MC Neville and CW Daniel, eds. New York: Plenum Press. 1987:67–93.Google Scholar
  22. 22.
    Russo J, Russo IH. Toward a physiological approach to breast cancer prevention. Cancer Epidemiol Biomarkers_& Prevention 1994; 3:353–64.Google Scholar
  23. 23.
    Russo J, Lynch H, Russo IH. Mammary gland architecture as a determining factor in the susceptibility of the human breast to cancer. Breast Journal 2001; 7(5):278–91.CrossRefPubMedGoogle Scholar
  24. 24.
    Russo J, Balogh GA, Chen J et al. The concept of stem cell in the mammary gland and its implication in morphogenesis, cancer and prevention. Frontiers in Bioscience 2006; 11:151–72.CrossRefPubMedGoogle Scholar
  25. 25.
    Balogh GA, Heulings R, Mailo DA et al. Genomic Signature Induced by Pregnancy in the Human Breast. Int J Oncol 2006; 28:399–410.PubMedGoogle Scholar
  26. 26.
    Russo J, Balogh GA, Heulings R et al. Molecular basis of pregnancy induced breast cancer protection. Eur J Cancer Prev 2006; 15:306–42.CrossRefPubMedGoogle Scholar
  27. 27.
    Russo J, Russo IH. Development pattern of human breast and susceptibility to carcinogenesis. Eur J Cancer Prev 1993; 2(Suppl 3):85.PubMedGoogle Scholar
  28. 28.
    Milanese TR, Hartmann LC, Sellers TA et al. Age-related lobular involution and risk of breast cancer. J Natl Cancer Inst 2006; 98:1600–7.PubMedCrossRefGoogle Scholar
  29. 29.
    Harvey JA, Santen RJ, Petroni GR et al. Histology findings of Mammographically Dense—Breast Tissue in Postmenopausal Women with and without Hormone Replacement Therapy. Breast Cancer Res Treat 2004; 88(Suppl 1):5008a.Google Scholar

Copyright information

© Landes Bioscience and Springer Science+Business Media 2008

Authors and Affiliations

  1. 1.Breast Cancer Research LaboratoryFox Chase Cancer CenterPhiladelphiaUSA

Personalised recommendations