Skip to main content
Log in

Phase II evaluation of interferon added to tamoxifen in the treatment of metastatic breast cancer

  • Report
  • Published:
Breast Cancer Research and Treatment Aims and scope Submit manuscript

Abstract

This phase II trial evaluated the clinical role of interferon (IFN) in overcoming tamoxifen (TAM) resistance in breast cancer. Twenty women and 1 man received recombinant alpha interferon (5 million units per meter squared intramuscularly, 5 times per week) plus TAM (10 mg orally, twice daily) for the treatment of metastatic breast cancer, either after failing tamoxifen therapy or as frontline hormonal therapy.

Of the 9 evaluable patients with disease progression after an objective response to TAM, there were no partial or complete responses with the addition of IFN. Ten evaluable patients received TAM plus IFN as frontline hormonal therapy with 2 complete and 3 partial responses for an overall response rate (RR) of 50% (95% confidence interval =19–81), a 71% RR for ER-positive patients (95% confidence interval =29–96) and no responses in ER-unknown patients.

Sixteen patients required dose reductions of IFN and 8 patients discontinued therapy due to toxicity.

It is unlikely that the RR for TAM plus IFN is greater that than seen with TAM alone, or that the addition of IFN to TAM therapy can overcome clinical TAM resistance.

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. Kiang DJ, Kollander RE, Thomas T, Kennedy BJ: Upregulation of estrogen receptors by nonsteroidal antiestroger in human breast cancer. Cancer Res 49: 5312–5316, 1989

    Google Scholar 

  2. Allegra JC, Lippman ME, Thompson EB, Simon R, Barlock A, Green L, Huff KK, Do HMT, Aitken SC, Warren R: Estrogen receptor status: an important variable in predicting response to endocrine therapy in metastatic breast cancer. Eur J Cancer 16: 323–331, 1980

    Google Scholar 

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

    Google Scholar 

  4. Waseda N, Kato Y, Imura H, Kurata M: Effects of tamoxifen on estrogen and progesterone receptors in human breast cancer. Cancer Res 41: 1984–1988, 1981

    Google Scholar 

  5. Marth C, Mayer I, Bock G, Gastl G, Huber C, Flener R, Daxenbichler G: Effects of human interferon alpha-2 and gamma on proliferation, estrogen receptor content, and sensitivity to anti-estrogens of cultured breast cancer cells. In: Dianzani F, Rosi GB (eds) Interferon System (Vol 24). Raven Press, New York, 1981, pp 367–371

    Google Scholar 

  6. Iacobelli S, Natoli C, Arno E, Sbarigia G, Gaggini C: An antiestrogenic action of interferons in human breast cancer cells. Anticancer Res 6: 1391–1394, 1986

    Google Scholar 

  7. Sica G, Natoli V, Stella C, delBianco S: Effects of natural beta-interferon on cell proliferation and steroid receptor level in human breast cancer cells. Cancer 60: 2419–2423, 1987

    Google Scholar 

  8. Denz H, Lechleitner M, Marth C, Daxenbichler G, Gastl G, Braunsteiner H: Effect on human recombinant alpha-2 and gamma-interferon of the growth of human cell lines from solid tumors and hematologic malignancies. J Interferon Res 5: 147–157, 1985

    Google Scholar 

  9. Gutterman JU, Blumenschein GR, Alexanian R, Yap HY, Buzdar AU, Cabanillas F, Hortobagyi GN, Hersh EM, Rasmussen SL, Harmon M, Kramer M, Pestka S: Leukocyte interferon-induced tumor regression in human metastatic breast cancer, multiple myeloma and malignant lymphoma. Ann Intern Med 93: 399–406, 1980

    Google Scholar 

  10. Borden EC, Holland JF, Dao TL, Gutterman JU, Wiener L, Chang YC, Patel J: Leukocyte-derived interferon (alpha) in human breast carcinoma. Ann Intern Med 97: 1–6, 1982

    Google Scholar 

  11. Laszlo J, Hood L, Cox E, Goodwin B: A randomized trial of low doses of alpha interferon in patients with breast cancer. J Biol Resp Mod 5: 206–210, 1986

    Google Scholar 

  12. Fentiman IS, Balkwill FR, Cuzick J, Haywad JL, Rubens RD: A trial of human alpha interferon as an adjuvant agent in breast cancer after loco-regional recurrence. Eur J Surg Oncol 13: 425–428, 1987

    Google Scholar 

  13. Dimitrov NV, Meyer CJ, Strander H, Einhorn S, Cantell K: Interferon as a modifier of estrogen receptors. Ann Clin Lab Sci 14: 32–39, 1984

    Google Scholar 

  14. van der Berg HW, Leahey WJ, Lynch M, Clarke R, Nelson J: Recombinant human interferon alpha increases oestrogen receptor expression in human breast cancer cells (ZR-75-1) and sensitises them to the anti-proliferative effect of tamoxifen. Br J Cancer 55: 255–257, 1987

    Google Scholar 

  15. Goldsteine D, Bushmeyer SM, Witt PL, Jordan VC, Borden EC: Effects of type I and II interferons on cultured human breast cells: interaction with estrogen receptors and with tamoxifen. Cancer Res 49: 2698–2702, 1989

    Google Scholar 

  16. Pouillart P, Palangie T, Jouve M, Garcia-Giralt E, Fridman WH, Magdelenat H, Falcoff E, Billiau A: Administration of fibroblast interferon to patients with advanced breast cancer: possible effects on skin metastasis and on hormone receptors. Eur J Cancer Clin Oncol 18: 929–935, 1982

    Google Scholar 

  17. Kauppila A, Cantell K, Janne O, Kokko E, Vihko R: Serum sex steroid and peptide hormone concentrations, and endometrial estrogen and progestin receptor levels during administration of human leukocyte interferon. Int J Cancer 29: 291–294, 1982

    Google Scholar 

  18. Hayward JL, Carbone PP, Heuson JC, Kamaoka S, Segaloff A, Rubens RD: Assessment of response to therapy in advanced breast cancer. Cancer 39: 1289–1294, 1977

    Google Scholar 

  19. Gehan EA: The determination of the number of patients required in a preliminary and a follow-up trial of a new chemotherapeutic agent. J Chron Dis 12: 346–353, 1961

    Google Scholar 

  20. Darbre PD, Glover JF, King RJ: Effects of steroids and their antagonists on breast cancer cells: therapeutic implications. In: Eppenberger U, Goldhirsch A (eds) Endocrine Therapy and Growth Regulation of Breast Cancer (Vol 14). Springer Verlag, Berlin, 1989, pp 16–28

    Google Scholar 

  21. Robinson SP, Jordan VC: Antiestrogen action of toremifene on hormone-dependent,-independent, and heterogeneous breast tumor growth in the athymic mouse. Cancer Res 49: 1758–1762, 1989

    Google Scholar 

  22. Darbre PD, King RJ: Progression to steorid insensitivity can occur irrespective of the presence of functional steroid receptors. Cell 51: 521–528, 1987

    Google Scholar 

  23. Reddel RR, Alexander IE, Koga M, Shrine J, Sutherland RL: Genetic instability and the development of steorid hormone insensitivity in cultured T47D human breast cancer cells. Cancer Res 48: 4340–4347, 1988

    Google Scholar 

  24. Robinson SP, Goldstein D, Witt PL, Borden EC, Jordan VC: Inhibition of hormone-dependent and independent breast cancer cell growthin vivo andin vitro with the antiestrogen toremifene and recombinant human interferon alpha. Breast Cancer Res Treat 15: 95–101, 1990

    Google Scholar 

Download references

Author information

Authors and Affiliations

Authors

Rights and permissions

Reprints and permissions

About this article

Cite this article

Macheledt, J.E., Buzdar, A.U., Hortobagyi, G.N. et al. Phase II evaluation of interferon added to tamoxifen in the treatment of metastatic breast cancer. Breast Cancer Res Tr 18, 165–170 (1991). https://doi.org/10.1007/BF01990032

Download citation

  • Issue Date:

  • DOI: https://doi.org/10.1007/BF01990032

Key words

Navigation