Skip to main content
Log in

Changes in the hormone receptors of human breast carcinoma xenografts in nude mice by treatment with cytotoxic agents

  • Original Articles
  • Published:
The Japanese journal of surgery Aims and scope Submit manuscript

Abstract

We examined the effect of chemotherapeutic agents on the estrogen receptors (ER) of breast carcinomasin vivo using human breast carcinoma strains (Br-10, T-61) serially transplanted into nude mice. When the tumor size reached approximately 1×1×1 cm, mitomycin C (MMC) at doses of 1, 2 and 4.5 mg/kg and cyclophosphamide (CPA) at a dose of 120 mg/kg, were administered once intraperitoneally, and the ERs of the tumors were measured sequentially by the dextran-coated charcoal method. Four days after the MMC administration at above doses, the binding sites of ER in Br-10 were not reduced and binding affinity was not affected. When the changes in ER content with time after the treatment with 4.5 mg/kg MMC and 120 mg/kg CPA were investigated, the ER content was found to be stable until 4 days after the treatment with both drugs, although the growth of T-61 had been significantly inhibited by the drugs. From these findings, it seems reasonable to initiate chemotherapy before endocrine therapy, since the chemotherapeutic agents did not reduce the ER content of the breast cancer strains.

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

Access this article

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

Instant access to the full article PDF.

Similar content being viewed by others

References

  1. Cooper R. Combination chemotherapy in human resistant breast cancer. Proc Am Assoc Cancer Res 1969; 10: 15.

    Google Scholar 

  2. Bonadonna G, Valagussa P, Rossi A, Tancini G, Brambila C, Zambetti M, Veronesi U. Ten year experience with CMF-based adjuvant chemotherapy in resectable breast cancer. Breast Cancer Res 1985; 5: 95–115.

    Article  CAS  Google Scholar 

  3. Abe O, Izuo M, Enomoto K, Kubo K, Koyama H, Sakai K, Terasawa T, Tominaga K, Nomura Y. Combination chemotherapy of cyclophosphamide, adriamycin and 5-fluorouracil (CAF) in advanced and recurrent breast cancer. Gan to Kagaku Ryohou (Jpn J Cancer Chemother) 1982; 9: 866–873. (in Japanese)

    CAS  Google Scholar 

  4. Nomura Y, Takatani O, Sugano H, Matsumoto K. Oestrogen and progesterone receptors and response to endocrine therapy in Japanese breast cancer. J Steroid Biochem 1980; 13: 565–566.

    Article  PubMed  CAS  Google Scholar 

  5. Mouridsen HT, Palshof T, Patterson J, Battersby L. Tamoxifen in advanced breast cancer. Cancer Treat Rev 1978; 5: 131–141.

    PubMed  CAS  Google Scholar 

  6. Pannuti F, DiMarco A, Martoni A. Medroxyprogesterone acetate in treatment of metastatic breast cancer. In: Role of medroxyprogesterone in endocrine-related tumors. New York: Raven Press 1982; 73–92.

    Google Scholar 

  7. Allegra JC, Barlock A, Huff KK, Lippman ME. Changes in multiple or sequential ER determinations in breast cancer. Cancer 1980; 45: 792–794.

    Article  PubMed  CAS  Google Scholar 

  8. Raam S, Nemeth E, Obrian S, Tamura H, Cohen JL. Immunohistochemical localization of estrogen receptors in human breast carcinoma using antireceptors antibodies. Proc Am Assoc Cancer Res 1981; 22: 10.

    Google Scholar 

  9. Yang KP, Samaan NA. Reduction of estrogen receptor concentration in MCF-7 human breast carcinoma cells following exposure to chemotherapeutic drugs. Cancer 1983; 43: 3534–3538.

    CAS  Google Scholar 

  10. Clarke R, Morwood J, van den Berg H, Nelson J, Murphy R. Effect of cytotoxic drugs on estrogen receptor expression and response to tamoxifen in MCF-7 cells, Cancer Res 1986; 46: 6116–6119.

    PubMed  CAS  Google Scholar 

  11. Kubota T, Shimosato Y, Nagai K. Experimental chemotherapy of carcinoma of the stomach and colon serially transplanted in nude mice. Gann 1977; 69: 299–309.

    Google Scholar 

  12. Hirohashi S, Shimosato Y, Kameya T, Nagai K, Tsunematsu R. Hormone dependency of a serially transplantable human breast cancer (Br-10) in nude mice. Cancer Res 1977; 37: 3184–3189.

    PubMed  CAS  Google Scholar 

  13. Kubota T, Kubouchi K, Koh J, Enomoto K, Ishibiki K, Abe O. Human breast carcinoma (MCF-7) serially transplanted into nude mice. Jpn J Surg 1983; 13: 381–384.

    Article  PubMed  CAS  Google Scholar 

  14. Brünner N, Spang-Thomsen M, Skovgaard SA, Engelholm A, Nielsen A, Vindelov L. Endocrine sensitivity of receptor positive T-61 human breast carcinoma serially grown in nude mice. Int J Cancer 1985; 35: 59–64.

    PubMed  Google Scholar 

  15. Geran RI, Greenberg NH, Macdonald MM, Shumacher AM, Abott BJ. Protocols for screening chemical and natural products against animal tumors and other biological systems. Cancer Chemother Rep 1972; 3: 51–61.

    Google Scholar 

  16. Yamasaki T. Estrogen receptor in malignant and benign breast tumors and normal tissues of Japanese patients. Jpn J Clin Oncol 1978; 8: 37–47.

    Google Scholar 

  17. Scatchard G. The attractions of proteins for small molecules and ions. Ann Sci 1949; 51: 660–672.

    CAS  Google Scholar 

  18. Ikeda T. Studies on progesterone receptors in malignant and benign breast tumors and normal breast tissues—in relation to estrogen receptor—. Keio Igaku (Journal of the Keio Medical Society) 1983; 60: 489–501. (in Japanese)

    CAS  Google Scholar 

  19. Clarke R, Morwood J, Nelson J, van den Berg H, Murphy R. The influence of vincristine on the oestrogen-binding capacity of two human breast cancer cell linesin vitro. Biochem Soc Trans 1986; 14: 449–450.

    CAS  Google Scholar 

  20. Cocconi G, De Lisi V, Boni C, Mori P, Malacarne P, Amadori D, Giovanelli E. Chemotherapyversus combination of chemotherapy and endocrine therapy in advanced breast cancer, a prospective randomized study. Cancer 1983; 51: 581–588.

    Article  PubMed  CAS  Google Scholar 

  21. Mouridsen HT, Palshof T, Engelman E, Sylvester R. CMFversus CMF plus tamoxifen in advanced breast cancer in postmenopausal woman. An EORTC trial. In: Mouridsen HT, Palshof T, eds. Breast cancer-experimental and clinical aspects. Oxford: Pergamon Press 1980; 119–123.

    Google Scholar 

  22. Fisher B, Redmond C, Brown A, Wolmark N, Wittliff J, Fisher E, Plotkin D, Bowman D, Sachs S, Wolter J, Frelik R, Desser R, Licalzi N, Geggie P, Campbell T, Elias GE, Prager D, Koontz P, Volk H, Dimitrov N, Gardner B, Lerner H, Shibata H. Treatment of primary breast cancer with chemotherapy and tamoxifen. N Engl J Med 1981; 305: 1–6.

    Article  PubMed  CAS  Google Scholar 

  23. Hubay CA, Pearson OH, Marshall JS, Stellato TA, Rhodes RS, DeBanne SM, Rosenblatt J, Mansour EG, Hermann RE, Jones JC, Flynn WJ, Eckert C, McGuire WL. Adjuvant therapy of stage II breast cancer 48-month follow-up of a prospective randomized clinical trial. Breast Cancer Res Treat 1981; 1: 77–82.

    Article  PubMed  CAS  Google Scholar 

  24. Kardinal CG, Perry MC, Weinberg V, Wood W, Ginsberg S, Raju RN. Chemoendocrine therapyvs chemotherapy alone for advanced breast cancer in postmonopausal woman. Breast Cancer Res Treat 1983; 3: 365–372.

    Article  PubMed  CAS  Google Scholar 

  25. Bezwoda WR, Derman D, DeMoor NG, Lange M, Levin J. Treatment of metastatic breast cancer in estrogen receptor positive patients, a randomized trial comparing tamoxifen aloneversus tamoxifen plus CMF. Cancer 1982; 50: 2747–2750.

    Article  PubMed  CAS  Google Scholar 

  26. Kubota T, Kubouchi K, Koh J, Asanuma F, Enomoto K, Ishibiki K, Abe Ol Combined cytotoxic and endocrine therapy for human breast carcinoma (Br-10) serially transplanted into nude mice. Jpn J Surg 1984; 14: 78–84.

    Article  PubMed  CAS  Google Scholar 

  27. Koh J. Experimental chemo and chemoendocrine therapy of human breast carcinomas serially transplanted into nude mice. Nippon Geka Gakkai Zasshi (J Jpn Surg Soc) 1988; 89: 91–102. (in Japanese with English Abst.)

    PubMed  CAS  Google Scholar 

  28. Enomoto K, Abe O. The evaluation of adjuvant chemoendocrine therapy for breast cancers. —Comparison of tegafur and tegafur+tamoxifen — Gan no Rinsho (Jpn J Cancer Clinic) 1987; suppl. 13: 165–181. (in Japanese)

    Google Scholar 

Download references

Author information

Authors and Affiliations

Authors

Rights and permissions

Reprints and permissions

About this article

Cite this article

Koh, Ji., Shiina, E., Hosoda, Y. et al. Changes in the hormone receptors of human breast carcinoma xenografts in nude mice by treatment with cytotoxic agents. The Japanese Journal of Surgery 20, 89–96 (1990). https://doi.org/10.1007/BF02470719

Download citation

  • Received:

  • Issue Date:

  • DOI: https://doi.org/10.1007/BF02470719

Key Words

Navigation