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Vol. 57, No. 4, 1999
Issue release date: November 1999
Oncology 1999;57:330–340
(DOI:10.1159/000012052)

Plasma Insulin-Like Growth Factor-I and Serum IGF-Binding Protein 3 Can Be Associated with the Progression of Breast Cancer, and Predict the Risk of Recurrence and the Probability of Survival in African-American and Hispanic Women

Vadgama J.V. · Wu Y. · Datta G. · Khan H. · Chillar R.
Department of Medicine, Divisions of Laboratory Research and Development and Hematology/Oncology, Charles R. Drew University of Medicine and Science, and UCLA School of Medicine, Los Angeles, Calif., USA

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Abstract

In vitro studies have shown that insulin-like growth factor (IGF) is a mitogen for breast cancer cells. However, the associations of plasma IGF-I with tumor histopathology in high-risk groups need further investigation. We hypothesize that plasma IGF-I and serum IGFBP3 concentrations in breast cancer patients may provide useful information on the progression of their disease, and determine the probability of recurrence and survival. We have carried out a retrospective study on 130 minority breast cancer patients. Plasma IGF-I and serum IGFBP3 were correlated with tumor histopathology, menopausal status, treatment modality, recurrence rates, and probability of survival. Plasma IGF-I and serum IGFBP3 were measured by radioimmunoassay. Our studies show that breast cancer patients have elevated plasma IGF-I and serum IGFBP3 levels. In addition we observed the following: IGF-I did not correlate with age and nodal stage. IGF-I and IGFBP3 increased with tumor size (T4). IGF-I did not correlate with estrogen receptor status, but did increase in progesterone-receptor-positive patients. IGF-I levels were higher in premenopausal patients and in women with cancer recurrence. Tamoxifen reduced IGF-I levels significantly and reduced the risk of recurrence. The survival probability was greater in patients with plasma IGF-I levels <120 ng/ml. In conclusion, lowering of plasma IGF-I may offer the following benefits: (a) reduce the risk of developing breast cancer in high-risk groups; (b) slow the progression of breast cancer in patients at early stages of cancer; (c) lower the risk of recurrence, and (d) increase the probability of survival.

Copyright © 1999 S. Karger AG, Basel



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References

  1. Daughaday WH, Rotwein P: Insulin-like growth factors I and II. Peptide, messenger ribonucleic acid and gene structures, serum, and tissue concentrations. Endocr Rev 1989;10:68–91.
  2. Werner H, Adamo M, Roberts CT Jr, LeRoith D: Molecular and cellular aspects of insulin-like growth factor action. Vitam Horm 1994;48:1–58.
  3. Shimatsu A, Rotwein P: Mosaic evolution of the insulin-like growth factors. Organization, sequence and expression of the rat insulin-like growth factor I gene. J Biol Chem 1987;262:7894–7900.
  4. Clemmons D: IGF binding proteins: Regulation of cellular actions. Growth Regul 1992;2:80–87.
  5. Werner H, Woloschack M, Stannard B, Shen-Orr Z, Roberts CT Jr, LeRoith D: The insulin-like growth factor I receptor: Molecular biology, heterogeneity, and regulation; in LeRoith D (ed): Insulin-Like Growth Factors: Molecular and Cellular Aspects. Boca Raton, CRC Press, 1991, pp 17–47.
  6. Werner H, LeRoith D: The role of the insulin-like growth factor system in human cancer; in Vande Woude GF, Klein G (eds): Advances in Cancer Research. New York, Academic Press, 1996, vol 68, pp 184–223.
  7. Pratt SE, Pollack MN: Estrogen and antiestrogen modulation of human breast cancer cell proliferation is associated with specific alterations in accumulation of insulin-like growth factor-binding proteins in conditioned media. Cancer Res 1993;53:5193–5198.
  8. Yee D, Jackson JG, Kozelsky TW, Figueroa JA: Insulin-like growth factor binding protein I expression inhibits insulin-like growth factor-I action in MCF-7 breast cancer cells. Cell Growth Differ 1994;5:73–77.
  9. Lee AV, Yee D: Insulin-like growth factors and breast cancer. Biomed Pharmacother 1995;49:415–421.
  10. Hankinson SE, Willett WC, Colditz GA, Hunter DJ: Circulating concentrations of insulin-like growth factor-1 and risk of breast cancer. Lancet 1998;351:1393–1396.
  11. Chan JM, Stampfer MJ, Giovannucci E, et al: Plasma insulin-like growth factor-I and prostate cancer risk: A prospective study. Science 1998;279:563–566.
  12. Barinaga M: Study suggests new way to gauge prostate cancer risk. Science 1998;279:475.
  13. Holly J: Insulin-like growth factor-1 and new opportunities for cancer prevention. Lancet 1998;351:1373–1374.

    External Resources

  14. Editorial: IGF binding protein-3 protease regulation: How sweet it is! J Clin Endocrinol Metab 1995;80:2279–2281.
  15. Jones JI, Clemmons DR: Insulin-like growth factors and their binding proteins: Biological actions. Endocr Rev 1995;16:3–16.
  16. Lahti EI, Knip M, Laatikainen TJ: Plasma insulin-like growth factor I and its binding proteins 1 and 3 in postmenopausal patients with breast cancer receiving long term tamoxifen. Cancer 1994;74:618–624.

    External Resources

  17. Rocha RL, Hilsenbeck S, Jackson J, et al: Insulin-like growth factor binding protein-3 and insulin receptor substrate-1 in breast cancer: Correlation with clinical parameters and disease free survival. Clin Cancer Res 1997;3:103–109.
  18. Rocha RL, Hilsenbeck SG, Jackson JG, et al: Correlation of insulin-like growth factor-binding protein-3 messenger RNA with protein expression in primary breast cancer tissues: Detection of higher levels in tumors with poor prognostic features. J Natl Cancer Inst 1996;88:601–606.

    External Resources

  19. Pratt S, Pollak M: Insulin-like growth factor binding protein 3 (IGFBP3) inhibits estrogen-stimulated breast cancer cell proliferation. Biochem Biophys Res Commun 1994;198:292–297.
  20. Buckbinder L, Talbott R, Velasco-Miguel S, et al: Induction of the growth inhibitor IGF-binding protein 3 by p53. Nature 1995;377:646–649.
  21. Huynh H, Yang X, Pollak M: A role for insulin-like growth factor binding protein 5 in the antiproliferative action of the antiestrogen ICI 182780. Cell Growth Differ 1996;7:1501–1506.

    External Resources

  22. Gucev Z, Oh Y, Kelley K, et al: Insulin-like growth factor binding protein 3 mediates retinoic acid- and transforming growth factor beta 2-induced growth inhibition in human breast cancer cells. Cancer Res 1996;56:1545–1550.
  23. Underwood LE, Murphy MG: Radioimmunoassay of the somatomedins/insulin-like growth factors; in Patrano C, Peskar BA (eds): Radioimmunoassay in Basic and Clinical Pharmacology. Berlin, Springer, 1987, pp 561–574.
  24. Chatelain PG, Van Wyk JJ, Copeland CC, et al: Effects of in vitro action of serum proteases or exposure to acid on measurable immunoreactive somatomedin C in serum. J Clin Endocrinol Metab 1983;56:376–383.

    External Resources

  25. Clemmons DR, Underwood LE, Chatelain PG, et al: Liberation of immunoreactive somatomedin-C from its binding proteins by proteolytic enzymes and heparin. J Clin Endocrinol Metab 1983;56:384–389.

    External Resources

  26. Daughaday WH, Kapadia M, Moriz I: Serum somatomedin binding proteins: Physiologic significance and interference in radioligand assay. J Lab Clin Med 1987;109:355–363.

    External Resources

  27. Daughaday WH, Mariz IK, Blethen SL: Inhibition of access of basic somatomedin to membrane receptors and immunobinding sites. A comparison of radioreceptor and radioimmunological somatomedin in native and acid-ethanol extracted serum. J Clin Endocrinol Metab 1980;51:781–788.

    External Resources

  28. Baxter RC, Martin JL: Radioimmunoassay of growth factor hormone-dependent insulin-like growth factor binding protein in human plasma. J Clin Invest 1986;78:1504–1512.
  29. Yee D, Paik S, Lebovic GS, Marcus RR, Favoni RE, Cullen KJ, et al: Analysis of insulin-like growth factor I gene expression in malignancy: Evidence for a paracrine role in human breast cancer. Mol Endocrinol 1989;3:509–517.
  30. Dickson RB, Lippman M: Growth factors in breast cancer. Endocr Rev 1995;16:559–589.
  31. Clemmons DR, Underwood LE: Clinical Review 59: Uses of human insulin-like growth factor-I in clinical conditions. J Clin Endocrinol Metab 1994;79:4–6.
  32. Macaulay VM: Insulin-like growth factors and cancer. Br J Cancer 1992;65:311–320.
  33. LeRoith D, Baserga R, Helman L, Roberts CT: Insulin-like growth factor and cancer. NIH Conference. Ann Intern Med 1995;22:54–59.
  34. Pollak MN: Endocrine effects of IGF-I on normal and transformed breast epithelial cells. Breast Cancer Res Treat 1998;47:209–217.
  35. Yee D: The insulin-like growth factors and breast cancer – revisited. Breast Cancer Res Treat 1998;47:197–199.
  36. Pollak M, Costantino J, Polychronakos C, et al: Effect of tamoxifen on serum insulin-like growth factor I levels in stage I breast cancer patients. J Natl Cancer Inst 1990;82:1693–1697.
  37. Favoni RE, de Cupis A, Perrotta A, Sforzini S, Amoroso A, Pensa F, et al: Insulin-like growth factor-I (IGF-I) and IGF-binding proteins blood serum levels in women with early- and late-stage breast cancer: Mutual relationship and possible correlations with patients’ hormonal status. J Cancer Res Clin Oncol 1995;121:674–682.
  38. Peyrat JP, Bonneterre J, Hecquet B, Vennin P, Louchez MM, Fournier C, et al: Plasma insulin-like growth factor-I (IGF-I) concentrations in human breast cancer. Eur J Cancer 1993;29A:492–497.
  39. Friedl A, Jordan CV, Pollak M: Suppression of serum insulin-like growth factor I levels in breast cancer patients during adjuvant tamoxifen therapy. Eur J Cancer 1993;29A:1368–1372.
  40. Yamamoto H, Sohmiya M, Oka N, Kato Y: Effect of aging and sex on plasma insulin-like growth factor I (IGF-I) levels in normal adults. Acta Endocrinol (Copenh) 1991;124:497–500.
  41. Pekonen F, Partanen S, Makinen T, et al: Receptors for epidermal growth factor and insulin-like growth factor I and their relation to steroid receptors in human breast cancer. Cancer Res 1988;48:1343–1347.
  42. Peyrat JP, Bonneterre J, Beuscart R, et al: Insulin-like growth factor I receptors in human breast cancer and their relation to estradiol and progesterone receptors. Cancer Res 1988;48:6429–6433.
  43. Lippman ME, Bolan G: Oestrogen-responsive human breast cancer in long-term tissue culture. Nature (Lond) 1975;256:592–593.

    External Resources

  44. Cole M, Jones CT, Todd IDH: A new antiestrogenic agent in late breast cancer: An early clinical appraisal of ICI 46,474. Br J Cancer 1971;25:270–275.
  45. Colletti RB, Roberts JD, DeVlin JT, Copeland KC: Effect of tamoxifen on plasma insulin-like growth factor I in patients with breast cancer. Cancer Res 1989;49:1882–1884.
  46. Helle SI, Holly JM, Tally M, et al: Influence of treatment with tamoxifen and change in tumor burden on the IGF-system in breast cancer patients. Int J Cancer 1996;69:335–339.
  47. Helle SI, Anker GB, Tally M, et al: Influence of droloxifene on plasma levels of insulin-like growth factor (IGF)-I, Pro-IGF-IIE, insulin-like growth factor binding (IGFBP)-1 and IGFBP-3 in breast cancer patients. J Steroid Biochem Mol Biol 1996;57:167–171.

    External Resources

  48. Kawamura I, Lacey E, Mizota T, et al: The effect of droloxifene on the insulin-like growth factor-I-stimulated growth of breast cancer cells. Anticancer Res 1994;14:427–431.

    External Resources

  49. Bajetta E, Ferrai L, Celio L, et al: The aromatase inhibitor letrozole in advanced breast cancer: Effects on serum insulin-like growth factor (IGF)-I and IGF-binding protein-3 levels. J Steroid Biochem Mol Biol 1997;63:261–267.

    External Resources

  50. Frost VJ, Helle SI, Lonning PE, et al: Effects of treatment with megestrol acetate, aminoglutethimide, or formestane on insulin-like growth factor (IGF) I and II, IGF-binding proteins (IGFBPs), and IGFBP-3 protease status in patients with advanced breast cancer. J Clin Endocrinol Metab 1996;81:2216–2221.
  51. Guvakova M, Surmacz E: Tamoxifen interferes with the insulin-like growth factor-I receptor (IGF-IR) signaling pathway in breast cancer cells. Cancer Res 1997;57:2606–2610.

    External Resources

  52. Dunn SE, Hardman RA, Kari FW, Barrett JC: Insulin-like growth factor I (IGF-I) alters drug sensitivity of HBL100 human breast cancer cells by inhibition of apoptosis induced diverse anticancer drugs. Cancer Res 1997;57:2687–2693.
  53. Helle SI, Lonning PE: Insulin-like growth factors in breast cancer. Acta Oncol 1996;35(suppl 5):19–22.


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