Skip to main content

Advertisement

SpringerLink
Log in

Metastatic view of breast cancer

  • NON-THEMATIC REVIEW
  • Published:
Cancer and Metastasis Reviews Aims and scope Submit manuscript

Abstract

The ancient view regarding breast cancer as a metastasis has not been supported so far by experimental evidence. We have implanted nephroblastoma tumor cells resulting in a rat metastatic kidney capsule–parathymic lymph node (PTN) model. India ink implantation confirmed the lymphatic connection between the primary tumor of the kidney and PTNs. 18F-FDG glucose analog distribution provided further evidence that the first metastatic sites of distant tumor progression are PTNs. Tumor invasion caused disruptions in the tissue of the primary renal tumor, releasing cancer cells into the peritoneal cavity. Colloidal particles, among them bacteria and India ink, crossed transdiaphragmatic channels drained from the peritonel cavity to the thoracic lymphatics and entered not only in the parathymic lymph nodes but also in the anterior mammary lymph nodes. The kidney capsule–PTN complex is reflecting a so far unknown mechanism of tumor development and suggests a similar tumor progression directed towards mammary lymph nodes. The mammalian tumor model provides a reasonable explanation for breast cancer development viewed as a metastasis, rather than a primary tumor.

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

Access this article

Log in via an institution

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Fig. 1
Fig. 2
Fig. 3

Similar content being viewed by others

References

  1. Chaffer, C. L., & Weinberg, R. A. (2011). A perspective on cancer cell metastasis. Science, 331, 1559–1564.

    Article  PubMed  CAS  Google Scholar 

  2. Allen, J. P., Allen, S. J., Patch, D. C., & Mininberg, D. T. (2005). The art of medicine in ancient Egypt (p. 70). New York: The Metropolitan Museum of Arts. http://medicineworld.org/cancer/history.html.

  3. Loris, P. (1970). Aselli, Gaspare. Dictionary of scientific biography (pp. 315–316). New York: Charles Scribner’s Sons.

    Google Scholar 

  4. James, O. (2002). Bathsheba’s breast: women, cancer, and history. Baltimore: John Hopkins Press.

    Google Scholar 

  5. Doe, J. (1960). Jean Astruc (1694–1766): a biography and bibliography. Journal of the History Medicine, 15, 184–197.

    Google Scholar 

  6. Halsted, W. S. (1894). The results of operations for the cure of cancer of the breast performed at the Johns Hopkins Hospital from June, 1899, to January, 1894. Annals of Surgery, 20, 497–555.

    Article  PubMed  CAS  Google Scholar 

  7. Urban, J. A., & Baker, H. W. (1952). Radical mastectomy in continuity with en bloc resection of the internal mammary lymph-node chain; a new procedure for primary operable cancer of the breast. Cancer, 5, 992–1008.

    Article  PubMed  CAS  Google Scholar 

  8. Stockwell, S. (1983). Classics in oncology: George Thomas Beatson, M.D. (1848–1933). Cancer Journal for Clinicians, 33, 105–107.

    Article  CAS  Google Scholar 

  9. Chodosh, L. A., D’Cruz, C. M., Gardner, H. P., Ha, S. I., Marquis, S. T., Rajan, J. V., Stairs, D. B., Wang, J. Y., & Wang, M. (1999). Mammary gland development, reproductive history, and breast cancer risk. Cancer Research, 59, 1765–1771.

    PubMed  CAS  Google Scholar 

  10. MacMahon, B., Cole, P., Lin, T. M., Lowe, C. R., Mirra, A. P., Ravnihar, B., Salber, E. J., Valaoras, V. G., & Yuasa, S. (1970). Age at first birth and breast cancer risk. Bulletin of the World Health Organization, 43, 209–221.

    PubMed  CAS  Google Scholar 

  11. Layde, P. M., Webster, L. A., Baughman, A. L., Wingo, P. A., Rubin, G. L., & Ory, H. W. (1989). The independent associations of parity, age at first full term pregnancy, and duration of breastfeeding with the risk of breast cancer. Cancer and Steroid Hormone Study Group. Journal of Clinical Epidemiology, 42, 963–973.

    Article  PubMed  CAS  Google Scholar 

  12. Huggins, C. B., Grand, L. C., & Brillantes, F. P. (1961). Mammary cancer induced by a single feeding of polymucular hydrocarbons, and its suppression. Nature (London), 189, 204–207.

    Article  CAS  Google Scholar 

  13. Huggins, C. B., Grand, L. C., & Oka, H. (1970). Hundred day leukemia: preferential induction in rat by pulse-doses of 7,8,12-trimethylbenz(a)anthracene. The Journal of Experimental Medicine, 131, 321–330.

    Article  PubMed  CAS  Google Scholar 

  14. Huggins, C. B., Ueda, N., & Wiessler, M. (1981). N-Nitroso-N-methylurea elicits mammary cancer in resistant and sensitive rat strains. Proceedings of the National Academy of Sciences USA, 78, 1185–1188.

    Article  CAS  Google Scholar 

  15. Luft, R., & Olivecrona, H. (1957). Hypophysectomy in the treatment of malignant tumors. Cancer, 10, 789–794.

    Article  PubMed  CAS  Google Scholar 

  16. Crile, G., Jr. (1967). A biological consideration of treatment of breast cancer (p. 189). Springfield: Charles C Thomas Publisher.

    Google Scholar 

  17. Travis, K. (2005). Bernard Fisher reflects on a half-entury’s worth of breast cancer research. Journal of the National Cancer Institute, 97, 1636–1637.

    Article  PubMed  Google Scholar 

  18. Hellman, S. (1994). Karnofsky memorial lecture. Natural history of small breast cancers. Journal Clinical Oncology, 12, 2229–2234.

    CAS  Google Scholar 

  19. Weichselbaum, R. R., & Hellman, S. (2011). Oligometastases revisited. Nature Reviews Clinical Oncology, 8, 378–382.

    PubMed  CAS  Google Scholar 

  20. Hart, I. R., & Fidler, I. J. (1980). Cancer invasion and metastasis. Quarterly Review of Biology, 55, 121–142.

    Article  PubMed  CAS  Google Scholar 

  21. Marco, A. J., Domingo, M., Ruberte, J., Carretero, A., Briones, V., & Dominguez, L. (1992). Lymphatic drainage of Listeria monocytogenes and Indian ink inoculated in the peritoneal cavity of the mouse. Laboratory Animals, 26, 200–205.

    Article  PubMed  CAS  Google Scholar 

  22. Abernethy, N. J., Chin, W., Hay, J. B., Rodela, H., Oreopoulos, D., & Johnston, M. G. (1991). Lymphatic drainage of the peritoneal cavity in sheep. American Journal of Physiology, 260, F353–F358.

    PubMed  CAS  Google Scholar 

  23. Pereira, C. T., Luiz Navarro Marques, F., Williams, J., Wlademir De Martin, B., & Primo Bombonato, P. (2008). 99mTc-labeled dextran for mammary lymphoscintigraphy in dogs. Veterinary Radiology & Ultrasound, 49, 487–491.

    Article  Google Scholar 

  24. Morcos, M. B., Lotfi, Z. S., Sabban, M. A., Ibrahim, M. S., & Nada, S. M. (1977). Mastitis concomitant with traumatic reticulo-peritonitis in buffaloes. Annales de Recherches Vétérinaires, 8, 221–225.

    PubMed  CAS  Google Scholar 

  25. Nagy, J. A. (1992). Lymphatic and nonlymphatic pathways of peritoneal absorption in mice: physiology versus pathology. Blood Purification, 10, 148–162.

    Article  PubMed  CAS  Google Scholar 

  26. Banfalvi, G. (2012). Role of parathymic lymph nodes in metastatic tumor development. Cancer and Metastasis Reviews, 31, 89–97. doi:10.1007/s10555-011-9331-y.

    Article  PubMed  Google Scholar 

  27. Trencsenyi, G., Kertai, P., Bako, F., Hunyadi, J., Marian, T., Hargitai, Z., Pocsi, I., Muranyi, E., Hornyak, L., & Banfalvi, G. (2009). Renal capsule–parathymic lymph node complex: a new in vivo metastatic model in rats. Anticancer Research, 29, 2121–2126.

    PubMed  Google Scholar 

  28. Kamperdijk, E. W. A., van den Berg, M., & Hoefsmit, E. C. M. (1984). Lymph node accessory cells in the immune response. The primary response to paratyphoid vaccine in rat parathymic lymph nodes. Cell and Tissue Research, 237, 39–42.

    Article  PubMed  CAS  Google Scholar 

  29. Trencsenyi, G., Juhasz, T., Bako, F., Marian, T., Pocsi, I., Kertai, P., Hunyadi, J., & Banfalvi, G. (2010). Comparison of the tumorigenic potential of liver and kidney tumors induced by N-nitrosodimethylamine. Histology and Histopathology, 25, 309–320.

    PubMed  CAS  Google Scholar 

  30. Steer, H. W., & Foot, R. A. (1987). Changes in the medulla of the parathymic lymph nodes of the rat during acute gastro-intestinal inflammation. Journal of Anatomy, 152, 23–36.

    PubMed  CAS  Google Scholar 

  31. Nandi, S., Guzman, R. C., & Yang, J. (1995). Hormones and mammary carcinogenesis in mice, rats and humans: a unifying hypothesis. Proceeding of the National Academy of Sciences, USA, 92, 3650–3657.

    Article  CAS  Google Scholar 

  32. Patsikas, M. N., & Dessiris, A. (1996). The lymph drainage of the mammary glands in the Bitch: a lymphographic study. Part II: the 3rd mammary gland. Anatomia, Histologia, Embryologia, 25, 139–143.

    Article  PubMed  CAS  Google Scholar 

  33. Jardines, L., Goyal, S., Royce, M., Jaiyesimi, I., & Shari B. Goldfarb, S. B. (2012). Stages III and IV breast cancer. In: D. G. Haller, L. D. Wagman, K. A. Camphausen, & William J. Hoskins (Eds.), Cancer management: a multidisciplinary approach (14th Edition). Norwalk, CT, UBM Medica, 2012. http://www.ubmmedica.com

  34. Suwatanapongched, T., & Gierada, D. S. (2006). CT of thoracic lymph nodes. Part I: anatomy and drainage. British Journal of Radiology, 79, 922–928.

    Article  PubMed  CAS  Google Scholar 

  35. Boorman, G., & Everitt, J. (2005). Neoplastic disease in the laboratory rat. In M. Suckow, S. Weisbroth, & C. Franklin (Eds.), 2nd Edition American College of Laboratory Animal Medicine. Toronto: Academic.

    Google Scholar 

  36. MacLennan, M. B., Anderson, B. M., & Ma, D. W. L. (2011). Differential mammary gland development in FVB and C57Bl/6 mice: implications for breast cancer research. Nutrients, 3, 929–936.

    Article  PubMed  CAS  Google Scholar 

  37. Akewanlop, C., Watanabe, M., Singh, B., Walker, M., Kufe, D. W., & Hayes, D. F. (2001). Phagocytosis of breast cancer cells mediated by anti-MUC-1 monoclonal antibody, DF3, and its bispecific antibody. Cancer Research, 61, 4061–4065.

    PubMed  CAS  Google Scholar 

  38. Hsieh, C. C., & Trichopoulos, D. (1991). Breast size, handedness and breast cancer risk. European Journal of Cancer, 27, 131–135.

    Article  PubMed  CAS  Google Scholar 

  39. Ford, D., Easton, D. F., & Peto, J. (1995). Estimates of the gene frequency of BRCA1 and its contribution to breast and ovarian cancer incidence. American Journal of Human Genetics, 57, 1457–1462.

    PubMed  CAS  Google Scholar 

  40. Anglian Breast Cancer Study Group. (2000). Prevalence and penetrance of BRCA1 and BRCA2 mutations in a population-based series of breast cancer cases. British Journal of Cancer, 83, 1301–1308.

    Article  Google Scholar 

  41. Rozsa, D., Trencsenyi, G., Kertai, P., Marian, T., Nagy, G., & Banfalvi, G. (2009). Lymphatic spread of mesenchymal renal tumor to metastatic parathymic lymph nodes. Histolology and Histopathology, 24, 1367–1379.

    Google Scholar 

  42. Wood, K., Cameron, M., & Fitzgerald, K. (2008). Breast size, bra fit and thoracic pain in young women: a correlational study. Chiropractic and Osteopathy, 16, 1–7.

    Article  PubMed  Google Scholar 

  43. Vendrell-Torné, E., Setoain-Quinquer, J., & Domenech-Torné, F. M. (1972). Study of normal mammary lymphatic drainage using radioactive isotopes. Journal of Nuclear Medicine, 13, 801–805.

    PubMed  Google Scholar 

  44. Johnson, D., & Shah, P. (2005). Thorax. In S. Standring (Ed.), Gray’s anatomy (39th ed., pp. 951–1079). Edinburgh: Churchill Livingstone.

    Google Scholar 

Download references

Acknowledgments

This work was supported by the Hungarian Scientific Research Grant (OTKA Grant) T 42762 grant to G.B.

Author information

Authors and Affiliations

  1. Department of Microbial Biotechnology and Cell Biology, University of Debrecen, 1 Egyetem Square, Debrecen, 4010, Hungary

    Gaspar Banfalvi

Authors
  1. Gaspar Banfalvi
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to Gaspar Banfalvi.

Rights and permissions

Reprints and permissions

About this article

Cite this article

Banfalvi, G. Metastatic view of breast cancer. Cancer Metastasis Rev 31, 815–822 (2012). https://doi.org/10.1007/s10555-012-9392-6

Download citation

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s10555-012-9392-6

Keywords

Search

Navigation