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Prognostic value of epidermal growth factor receptor in node-positive breast cancer

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Summary

The prognostic significance of EGFR (epidermal growth factor receptor) was studied in a cohort of 68 node-positive patients with breast cancer, who entered a controlled protocol of adjuvant therapy between February 1980 and June 1984. EGFR radioligand binding assay was carried out on frozen stored samples. Twenty five (37%) of 68 primary sites and 9 (41%) of 19 lymph node metastases assayed were EGFR-positive with a cut off value of 5 fmol/mg membrane protein; there is no statistical difference between the two distributions. EGFR was significantly correlated to ER and histological grade. EGFR-positive tumors and high levels of EGFR were mainly found in the ER-negative group of tumors (p = 0.008) and in histological grade III (p = 0.007). Fifty five patients could be followed for 40 to 92 months. EGFR was an independent prognostic factor for survival after 40 months (p = 0.05). EGFR+/ER patients had the lowest survival probability, but statistical significance was not reached (p = 0.06). The EGFR phenotype appeared as a prognostic parameter in node-positive patients, individualizing subgroups of patients with different early outcome, with potential therapeutic implication especially in the group of ER-negative patients. These results emphasize the need for a standardized assay methodology and for further clinical studies, particularly in protocols where adjuvant hormonal therapy is prescribed on the basis of steroid hormone receptor status, in order to assess the respective prognostic worth of EGFR and ER (or PR).

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References

  1. Carpenter G, Cohen S: Epidermal growth factor. Ann Rev Biochem 48: 198–216, 1979

    Google Scholar 

  2. Fitzpatrick SL, Lachance MP, Schultz GS: Characterization of epidermal growth factor receptor and action on human breast cancer cells in culture. Cancer Res 44: 3442–3447, 1984

    PubMed  Google Scholar 

  3. Carpenter G: Properties of the receptor for epidermal growth factor. Cell 37: 357–358, 1984

    PubMed  Google Scholar 

  4. Carpenter G: Receptors for epidermal growth factor and other polypetide mitogens. Ann Rev Biochem 56: 881–914, 1987

    PubMed  Google Scholar 

  5. Roberts AB, Frolick CA, Anzano MA, Sporn MB: Transforming growth factors from neoplastic and non-neoplastic tissues. Fed Proc 42: 2621–2625, 1983

    PubMed  Google Scholar 

  6. Sporn MB, Roberts AB: Autocrine growth factors and cancer. Nature 313: 747–751, 1985

    Google Scholar 

  7. Lippman ME, Dickson RB, Bates S, Knabbe C, Huff K, Swain S, McManaway M, Bronzert D, Kassid A, Gelmann EP: Autocrine and paracrine growth regulation of human breast cancer. Breast Cancer Res Treat 7: 59–70, 1986

    PubMed  Google Scholar 

  8. Ozanne B, Shum A, Richards CS, Cassells D, Grossman D, Trent J, Gusterson B, Hendler F: Evidence for an increase of EGF receptors in epidermoid malignancies. In Cancer Cells: Growth Factors and Transformation Cold Spring Harbor Laboratory. pp 41–48, 1985

  9. Fitzpatrick SL, Brightwell J, Wittliff JL, Barrows GH, Schultz GS: Epidermal growth factor binding by breast tumor biopsies and relationship to estrogen receptor and progestin receptor levels. Cancer Res 44: 3448–3453, 1984

    PubMed  Google Scholar 

  10. Perez R, Pasqual M, Macias A, Loge A: Epidermal growth factor receptors in human breast cancer. Breast Cancer Res Treat 4: 189–193, 1984

    PubMed  Google Scholar 

  11. Sainsbury JRC, Farndon JR, Sherbet GV, Harris AL: Epidermal growth factor receptors and oestrogen receptors in human breast cancer. Lancet 1: 364–366, 1985

    PubMed  Google Scholar 

  12. Grimaux M, Remvikos Y, Magdelenat H: Récepteurs d'EGF et récepteurs hormonaux dans les tumeurs mammaires (Abstract). Bull Cancer 74: 687, 1987

    Google Scholar 

  13. Cappelletti V, Brivio M, Miodini P, Granata G, Coradini D, Di Fronzo G: Simultaneous estimation of epidermal growth factor receptors and steroid receptors in a series of 136 resectable primary breast tumors. Tumor Biol 9: 200–211, 1988

    Google Scholar 

  14. Delarue JC, Friedman S, Mouriesse H, May-Levin F, Sancho-Garnier H, Contesso G: Epidermal growth factor receptor in human breast cancers: correlation with estrogen and progesterone receptors. Breast Cancer Res Treat 11: 173–178, 1988

    PubMed  Google Scholar 

  15. Sainsbury JRC, Malcolm AJ, Appleton DR, Farndon JR, Harris AL: Presence of epidermal growth factor receptor as an indicator of poor prognosis in patients with breast cancer. J Clin Pathol 38: 1225–1228, 1985

    PubMed  Google Scholar 

  16. Skoog L, Macias A, Azavedo E, Lombardero J, Klintenberg C: Receptors for EGF and oestradiol and thymidine kinase activity in different histological subgroups of human mammary carcinomas. Br J Cancer 54: 271–276, 1986

    PubMed  Google Scholar 

  17. Walker RA, Camplejohn RS: DNA flow cytometry of human breast carcinomas and its relationship to transferrin and epidermal growth factor receptors. J Pathol 150: 37–42, 1986

    PubMed  Google Scholar 

  18. Macias A, Azavedo E, Hägerstrom T, Klintenberg C, Perez R, Skoog L: Prognostic significance of the receptor for epidermal growth factor in human mammary carcinomas. Anticancer Res 7: 459–464, 1987

    PubMed  Google Scholar 

  19. Spitzer E, Grosse R, Kunde D, Schmidt HE: Growth of mammary epithelial cells in breast-cancer biopsies correlates with EGF binding. Int J Cancer 39: 279–282, 1987

    PubMed  Google Scholar 

  20. Cattoretti G, Rilke F, Andreola S, D'Amato L, Delia D: P53 expression in breast cancer. Int J Cancer 41: 178–183, 1988

    PubMed  Google Scholar 

  21. Sainsbury JCR, Farndon JR, Needham GK, Malcolm AJ, Harris AL: Epidermal growth factor receptor status as predictor of early recurrence of and death from breast cancer. Lancet 1: 1398–1402, 1987

    PubMed  Google Scholar 

  22. Rios MA, Macias A, Pérez R, Lage A, Skoog L: Receptors for epidermal growth factor and estrogen as predictors of relapse in patients with mammary carcinoma. Anticancer Res 8: 173–176, 1988

    PubMed  Google Scholar 

  23. Koenders A, Thorpe SM: Standardisation of steroid receptor assay in human breast III. Selection of reference material for intra and inter laboratory quality control. Eur J Cancer Clin Oncol 22: 939–944, 1986

    PubMed  Google Scholar 

  24. Grimaux M, Magdelenat H, Poisson M, Chamouard JM, Barritault D, Foncin JF, Philippon J: Récepteurs d'EGF (Epidermal growth factor) et de stéroïdes dans les méningiomes humains. Rev Neurol (Paris) 144: 96–103, 1988

    Google Scholar 

  25. Fiszer-Szafarz B, Szafarz D, Guevava de Murillo A: A general fast and sensitive micromethod for DNA determination. Analyt Biochem, 110: 165–170, 1981

    PubMed  Google Scholar 

  26. Bradford MM: A rapid and sensitive method for the quantitation of microgram quantities of protein utilizing the principle of protein-dye binding. Analyt Biochem 72: 248–254, 1976

    PubMed  Google Scholar 

  27. Savage CR, Cohen S: Epidermal growth factor and a new derivative. Rapid isolation procedures and biological and chemical characterization. J Biol Chem 247: 7609–7611, 1972

    PubMed  Google Scholar 

  28. Elson SD, Browne CA, Thorburn GD: Extraction and purification of murine epidermal growth factor. Biochem Internat 8: 427–435, 1984

    Google Scholar 

  29. Weisman AS, Raguet SS, Kelly PA: Characterization of the epidermal growth factor receptor in human meningioma. Cancer Res 47: 2172–2176, 1987

    PubMed  Google Scholar 

  30. Fabricant RN, DeLarco JE, Todaro GJ: NGF receptors on human melanoma cells in culture. Proc Natl Acad Sci USA 74: 565–569, 1977

    PubMed  Google Scholar 

  31. Kendall MG: Rank Correlation Methods (3rd ed). Hafner, New York, 1962

    Google Scholar 

  32. Young IT: Proof without prejudice. Use of the Kolmogorov-Smirnov test for the analysis of histograms from flow systems and other sources. J Histochem Cytochem 25: 935–941, 1977

    PubMed  Google Scholar 

  33. Mantel N: Evaluation of survival data and two new rank order statistics arising in its consideration. Cancer Chemother Rep 50: 163–170, 1966

    PubMed  Google Scholar 

  34. Cox DR: Regression models and life tables. J R Stat Soc 34: 187–202, 1972

    Google Scholar 

  35. Namer M: Bilan de l'hormonothérapie adjuvante et des associations hormono-chimiothérapiques adjuvantes. In Serin D ed. Cancer du Sein. Définition du risque métastatique. Bilan des thérapeutiques adjuvantes. Masson (Paris). pp 101–125, 1988

    Google Scholar 

  36. Bonadonna G, Valagussa P: The contribution of medicine to the primary treatment of breast cancer. Cancer Res 48: 2314–2324, 1988

    PubMed  Google Scholar 

  37. Clark GM, McGuire WL: Steroid receptors and other prog-nostic factors in primary breast cancer. Seminars in Oncology 15 (2, Suppl 1): 20–25, 1988

    Google Scholar 

  38. Meyer JS, Lee JY: Relationship of S phase fraction of breast carcinoma in relapse to duration of remission, estrogen receptor content, therapeutic responsiveness, and duration of survival. Cancer Res 40: 1890–1896, 1980

    PubMed  Google Scholar 

  39. Meyer JS: Cell kinetics and stratification of patients for adjuvant therapy of breast carcinoma. NCI Monographs 1: 25–28

  40. Tubiana A, Pejovic MH, Chavaudra N, Contesso G, Malaise EP: The long term prognostic significance of the kinetics labelling index in breast cancer. Int J Cancer 33: 441–445, 1984

    PubMed  Google Scholar 

  41. Nicholson S, Sainsbury JRC, Needham GK, Chambers P, Farndon JR, Harris AL: Quantitative assay of Epidermal Growth Factor Receptor in human breast cancer: Cut-off points of clinical relevance. Int J Cancer 42: 36–41, 1988

    PubMed  Google Scholar 

  42. Macias A, Azavedo A, Perez R, Rutqvist LE, Skoog L: Receptors for epidermal growth factor in mammary carcinomas and their metastases. Anticancer Res 6: 849–852, 1986

    PubMed  Google Scholar 

  43. Opferman M, Brugal G, Vassilakos P: Cytometry of breast carcinoma: significance of ploïdy balance and proliferation index. Cytometry 8: 217–224, 1987

    PubMed  Google Scholar 

  44. Remvikos Y, Gerbault-Seurreau M, Vielh P, Zafrani B, Magdelenat H, Dutrillaux B: Relevance of DNA ploïdy as a measure of genetic deviation: a comparison of flow cytometry and cytogenetic data in 25 cases of human breast cancer. Cytometry 9: 612–618, 1988

    PubMed  Google Scholar 

  45. Dressler LG, Seamer LG, Owens MA, Clark GM, McGuire WL: DNA flow cytometry and prognostic factors in 1331 frozen breast cancer specimens. Cancer 61: 420–427, 1988

    PubMed  Google Scholar 

  46. Pekonen F, Partanen S, Mäkinen T, Rutanen EM: Receptors for epidermal growth factor and insulin-like growth factor I and their relation to steroid receptors in human breast cancer. Cancer Res 48: 1343–1347, 1988

    PubMed  Google Scholar 

  47. Fisher B, Redmond C, Fisher ER, Caplan R, and other NSABP Investigators: Relative worth of estrogen or progesterone receptor and pathologic characteristics of differentiation as indicators of prognosis in node negative breast cancer patients: findings from NSABP protocl B-06. J Clin Oncol 6: 1076–1087, 1988

    PubMed  Google Scholar 

  48. Carpenter G, Stoscheck CH, Preston YA, De Larco JE: Antibodies to the epidermal growth factor receptor block the biological effects of sarcoma growth factor. Proc Natl Acad Sci USA 80: 5627–5634

  49. Kuratomi Y, Shin-Ishi A, Ono M, Shiraishi N, Shimada T, Ohkuma S, Kuwano M: Thioridazine enhances lysosomal accumulation of epidermal growth factor and toxicity of conjugates of epidermal growth factor with Pseudomonas endotoxin. Exp Cell Res 162: 436–448, 1986

    PubMed  Google Scholar 

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Grimaux, M., Romain, S., Remvikos, Y. et al. Prognostic value of epidermal growth factor receptor in node-positive breast cancer. Breast Cancer Res Tr 14, 77–90 (1989). https://doi.org/10.1007/BF01805978

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