C-myc amplification in breast cancer: a meta-analysis of its occurrence and prognostic relevance

Abstract

Data from basic research suggests that amplification of the proto-oncogene c-myc is important in breast cancer pathogenesis, but its frequency of amplification and prognostic relevance in human studies have been inconsistent. In an effort to clarify the clinical significance of c-myc amplification in breast cancer, we conducted a comprehensive literature search and a meta-analysis in which 29 studies were evaluated. The weighted average frequency of c-myc amplification in breast tumours was 15.7% (95% CI = 12.5-18.8%), although estimates in individual studies exhibited significant heterogeneity, P<0.0001. C-myc amplification exhibited significant but weak associations with tumour grade (RR = 1.61), lymph-node metastasis (RR = 1.24), negative progesterone receptor status (RR = 1.27), and postmenopausal status (RR = 0.82). Amplification was significantly associated with risk of relapse and death, with pooled estimates RR = 2.05 (95% CI = 1.51-2.78) and RR = 1.74 (95% CI = 1.27-2.39), respectively. This effect did not appear to be merely a surrogate for other prognostic factors. These results suggest that c-myc amplification is relatively common in breast cancer and may provide independent prognostic information. More rigorous studies with consistent methodology are required to validate this association, and to investigate its potential as a molecular predictor of specific therapy response.

References 49

1. 1.

   Adnane J., Gaudray P., Simon M. P., Simony-Lafontaine J., Jeanteur P., Theillet C. Proto-oncogene amplification and human breast tumor phenotype. Oncogene. 1989;4(11):1389-1395.

   Not in our library

2. 2.

   Alitalo K., Schwab M., Lin C. C., Varmus H. E., Bishop J. M. Homogeneously staining chromosomal regions contain amplified copies of an abundantly expressed cellular oncogene (c-myc) in malignant neuroendocrine cells from a human colon carcinoma. Proc Natl Acad Sci U S A. 1983;80(6):1707-1711.

   Not in our library10.1073/pnas.80.6.1707

3. 3.

   Berns E. M., Klijn J. G., van Putten W. L., van Staveren I. L., Portengen H., Foekens J. A. c-myc amplification is a better prognostic factor than HER2/neu amplification in primary breast cancer. Cancer Res. 1992;52(5):1107-1113.

   Not in our library

4. 4.

   Berns E. M., Klijn J. G., van Staveren I. L., Portengen H., Noordegraaf E., Foekens J. A. Prevalence of amplification of the oncogenes c-myc, HER2/neu, and int-2 in one thousand human breast tumours: correlation with steroid receptors. Eur J Cancer. 1992;28(2-3):697-700.

   Not in our library10.1016/s0959-8049(05)80129-7

5. 5.

   Bièche I., Champème M. H., Lidereau R. A tumor suppressor gene on chromosome 1p32-pter controls the amplification of MYC family genes in breast cancer. Cancer Res. 1994;54(16):4274-4276.

   Not in our library

6. 6.

   Bonilla M., Ramirez M., Lopez-Cueto J., Gariglio P. In vivo amplification and rearrangement of c-myc oncogene in human breast tumors. J Natl Cancer Inst. 1988;80(9):665-671.

   Not in our library10.1093/jnci/80.9.665

7. 7.

   Borg A., Baldetorp B., Fernö M., Olsson H., Sigurdsson H. c-myc amplification is an independent prognostic factor in postmenopausal breast cancer. Int J Cancer. 1992;51(5):687-691.

   Not in our library10.1002/ijc.2910510504

8. 8.

   Brouillet J. P., Theillet C., Maudelonde T., Defrenne A., Simony-Lafontaine J., Sertour J., Pujol H., Jeanteur P., Rochefort H. Cathepsin D assay in primary breast cancer and lymph nodes: relationship with c-myc, c-erb-B-2 and int-2 oncogene amplification and node invasiveness. Eur J Cancer. 1990;26(4):437-441.

   Not in our library10.1016/0277-5379(90)90012-i

9. 9.

   Champème M. H., Bièche I., Hacène K., Lidereau R. Oncogene amplification per se: an independent prognostic factor in human breast cancer. Mol Carcinog. 1994;11(4):189-191.

   Not in our library10.1002/mc.2940110403

10. 10.

    Cline M. J., Battifora H., Yokota J. Proto-oncogene abnormalities in human breast cancer: correlations with anatomic features and clinical course of disease. J Clin Oncol. 1987;5(7):999-1006.

    Not in our library10.1200/jco.1987.5.7.999

11. 11.

    Contegiacomo A., Pizzi C., De Marchis L., Alimandi M., Delrio P., Di Palma E., Petrella G., Ottini L., French D., Frati L. High cell kinetics is associated with amplification of the int-2, bcl-1, myc and erbB-2 proto-oncogenes and loss of heterozygosity at the DF3 locus in primary breast cancers. Int J Cancer. 1995;61(1):1-6.

    Not in our library10.1002/ijc.2910610102

12. 12.

    Courjal F., Cuny M., Simony-Lafontaine J., Louason G., Speiser P., Zeillinger R., Rodriguez C., Theillet C. Mapping of DNA amplifications at 15 chromosomal localizations in 1875 breast tumors: definition of phenotypic groups. Cancer Res. 1997;57(19):4360-4367.

    Not in our library

13. 13.

    Dalla-Favera R., Wong-Staal F., Gallo R. C. Onc gene amplification in promyelocytic leukaemia cell line HL-60 and primary leukaemic cells of the same patient. Nature. 1982;299(5878):61-63.

    Not in our library10.1038/299061a0

14. 14.

    Dang C. V. c-Myc target genes involved in cell growth, apoptosis, and metabolism. Mol Cell Biol. 1999;19(1):1-11.

    Not in our library10.1128/mcb.19.1.1

15. 15.

    Dickersin K., Berlin J. A. Meta-analysis: state-of-the-science. Epidemiol Rev. 1992;14:154-176.

    Not in our library10.1093/oxfordjournals.epirev.a036084

16. 16.

    Edwards P. A., Ward J. L., Bradbury J. M. Alteration of morphogenesis by the v-myc oncogene in transplants of mammary gland. Oncogene. 1988;2(4):407-412.

    Not in our library

17. 17.

    Escot C., Theillet C., Lidereau R., Spyratos F., Champeme M. H., Gest J., Callahan R. Genetic alteration of the c-myc protooncogene (MYC) in human primary breast carcinomas. Proc Natl Acad Sci U S A. 1986;83(13):4834-4838.

    Not in our library10.1073/pnas.83.13.4834

18. 18.

    Garcia I., Dietrich P. Y., Aapro M., Vauthier G., Vadas L., Engel E. Genetic alterations of c-myc, c-erbB-2, and c-Ha-ras protooncogenes and clinical associations in human breast carcinomas. Cancer Res. 1989;49(23):6675-6679.

    Not in our library

19. 19.

    George S. L., Desu M. M. Planning the size and duration of a clinical trial studying the time to some critical event. J Chronic Dis. 1974;27(1):15-24.

    Not in our library10.1016/0021-9681(74)90004-6

20. 20.

    Guérin M., Barrois M., Terrier M. J., Spielmann M., Riou G. Overexpression of either c-myc or c-erbB-2/neu proto-oncogenes in human breast carcinomas: correlation with poor prognosis. Oncogene Res. 1988;3(1):21-31.

    Not in our library

21. 21.

    Harada Y., Katagiri T., Ito I., Akiyama F., Sakamoto G., Kasumi F., Nakamura Y., Emi M. Genetic studies of 457 breast cancers. Clinicopathologic parameters compared with genetic alterations. Cancer. 1994;74(8):2281-2286.

    Not in our library10.1002/1097-0142(19941015)74:8<2281::aid-cncr2820740812>3.0.co;2-i

22. 22.

    Hayes D. F., Trock B., Harris A. L. Assessing the clinical impact of prognostic factors: when is "statistically significant" clinically useful? Breast Cancer Res Treat. 1998;52(1-3):305-319.

    Not in our library10.1023/a:1006197805041

23. 23.

    Janocko L. E., Lucke J. F., Groft D. W., Brown K. A., Smith C. A., Pollice A. A., Singh S. G., Yakulis R., Hartsock R. J., Shackney S. E. Assessing sequential oncogene amplification in human breast cancer. Cytometry. 1995;21(1):18-22.

    Not in our library10.1002/cyto.990210106

24. 24.

    Jenkins R. B., Qian J., Lieber M. M., Bostwick D. G. Detection of c-myc oncogene amplification and chromosomal anomalies in metastatic prostatic carcinoma by fluorescence in situ hybridization. Cancer Res. 1997;57(3):524-531.

    Not in our library

25. 25.

    Kreipe H., Feist H., Fischer L., Felgner J., Heidorn K., Mettler L., Parwaresch R. Amplification of c-myc but not of c-erbB-2 is associated with high proliferative capacity in breast cancer. Cancer Res. 1993;53(8):1956-1961.

    Not in our library

26. 26.

    Leder A., Pattengale P. K., Kuo A., Stewart T. A., Leder P. Consequences of widespread deregulation of the c-myc gene in transgenic mice: multiple neoplasms and normal development. Cell. 1986;45(4):485-495.

    Not in our library10.1016/0092-8674(86)90280-1

27. 27.

    Little C. D., Nau M. M., Carney D. N., Gazdar A. F., Minna J. D. Amplification and expression of the c-myc oncogene in human lung cancer cell lines. Nature. 1983;306(5939):194-196.

    Not in our library10.1038/306194a0

28. 28.

    Lönn U., Lönn S., Nilsson B., Stenkvist B. Prognostic value of erb-B2 and myc amplification in breast cancer imprints. Cancer. 1995;75(11):2681-2687.

    Not in our library10.1002/1097-0142(19950601)75:11<2681::aid-cncr2820751107>3.0.co;2-r

29. 29.

    Mertens F., Johansson B., Höglund M., Mitelman F. Chromosomal imbalance maps of malignant solid tumors: a cytogenetic survey of 3185 neoplasms. Cancer Res. 1997;57(13):2765-2780.

    Not in our library

30. 30.

    Meyers S. L., O'Brien M. T., Smith T., Dudley J. P. Analysis of the int-1, int-2, c-myc, and neu oncogenes in human breast carcinomas. Cancer Res. 1990;50(18):5911-5918.

    Not in our library

31. 31.

    Münzel P., Marx D., Köchel H., Schauer A., Bock K. W. Genomic alterations of the c-myc protooncogene in relation to the overexpression of c-erbB2 and Ki-67 in human breast and cervix carcinomas. J Cancer Res Clin Oncol. 1991;117(6):603-607.

    Not in our library10.1007/bf01613296

32. 32.

    Nagayama K., Watatani M. Analysis of genetic alterations related to the development and progression of breast carcinoma. Jpn J Cancer Res. 1993;84(11):1159-1164.

    Not in our library10.1111/j.1349-7006.1993.tb02816.x

33. 33.

    Nass S. J., Dickson R. B. Defining a role for c-Myc in breast tumorigenesis. Breast Cancer Res Treat. 1997;44(1):1-22.

    Not in our library10.1023/a:1005858611585

34. 34.

    Ottestad L., Andersen T. I., Nesland J. M., Skrede M., Tveit K. M., Nustad K., Børresen A. L. Amplification of c-erbB-2, int-2 and c-myc genes in node-negative breast carcinomas. Relationship to prognosis. Acta Oncol. 1993;32(3):289-294.

    Not in our library10.3109/02841869309093597

35. 35.

    Prados J., Melguizo C., Fernández A., Aránega A. E., Alvarez L., Aránega A. Inverse expression of mdr 1 and c-myc genes in a rhabdomyosarcoma cell line resistant to actinomycin d. J Pathol. 1996;180(1):85-89.

    Not in our library10.1002/(sici)1096-9896(199609)180:1<85::aid-path626>3.0.co;2-7

36. 36.

    Riva-Lavieille C. Chimiorésistance, oncogènes et anti-oncogènes dans les tumeurs épithéliales. Bull Cancer. 1994;81(Suppl 2):105s-111s.

    Not in our library

37. 37.

    Roux-Dosseto M., Romain S., Dussault N., Desideri C., Piana L., Bonnier P., Tubiana N., Martin P. M. c-myc gene amplification in selected node-negative breast cancer patients correlates with high rate of early relapse. Eur J Cancer. 1992;28A(10):1600-1604.

    Not in our library10.1016/0959-8049(92)90050-c

38. 38.

    Scorilas A., Yotis J., Gouriotis D., Keramopoulos A., Ampela K., Trangas T., Talieri M. Cathepsin-D and c-erb-B 2 have an additive prognostic value for breast cancer patients. Anticancer Res. 1993;13(5C):1895-1900.

    Not in our library

39. 39.

    Scorilas A., Yotis J., Stravolemos K., Gouriotis D., Keramopoulos A., Ampela K., Talieri M., Trangas T. c-erbB-2 overexpression may be used as an independent prognostic factor for breast cancer patients. Anticancer Res. 1995;15(4):1543-1547.

    Not in our library

40. 40.

    Sierra A., Castellsague X., Escobedo A., Moreno A., Drudis T., Fabra A. Synergistic cooperation between c-Myc and Bcl-2 in lymph node progression of T1 human breast carcinomas. Breast Cancer Res Treat. 1999;54(1):39-45.

    Not in our library10.1023/a:1006120006471

41. 41.

    Soengas M. S., Alarcón R. M., Yoshida H., Giaccia A. J., Hakem R., Mak T. W., Lowe S. W. Apaf-1 and caspase-9 in p53-dependent apoptosis and tumor inhibition. Science. 1999;284(5411):156-159.

    Not in our library10.1126/science.284.5411.156

42. 42.

    Tavassoli M., Quirke P., Farzaneh F., Lock N. J., Mayne L. V., Kirkham N. c-erbB-2/c-erbA co-amplification indicative of lymph node metastasis, and c-myc amplification of high tumour grade, in human breast carcinoma. Br J Cancer. 1989;60(4):505-510.

    Not in our library10.1038/bjc.1989.303

43. 43.

    Trock B. J., Leonessa F., Clarke R. Multidrug resistance in breast cancer: a meta-analysis of MDR1/gp170 expression and its possible functional significance. J Natl Cancer Inst. 1997;89(13):917-931.

    Not in our library10.1093/jnci/89.13.917

44. 44.

    Tsuda H., Hirohashi S., Shimosato Y., Hirota T., Tsugane S., Yamamoto H., Miyajima N., Toyoshima K., Yamamoto T., Yokota J. Correlation between long-term survival in breast cancer patients and amplification of two putative oncogene-coamplification units: hst-1/int-2 and c-erbB-2/ear-1. Cancer Res. 1989;49(11):3104-3108.

    Not in our library

45. 45.

    Varley J. M., Swallow J. E., Brammar W. J., Whittaker J. L., Walker R. A. Alterations to either c-erbB-2(neu) or c-myc proto-oncogenes in breast carcinomas correlate with poor short-term prognosis. Oncogene. 1987;1(4):423-430.

    Not in our library

46. 46.

    Varmus H. E. The molecular genetics of cellular oncogenes. Annu Rev Genet. 1984;18:553-612.

    Not in our library10.1146/annurev.ge.18.120184.003005

47. 47.

    Walker T. L., White J. D., Esdale W. J., Burton M. A., DeCruz E. E. Tumour cells surviving in vivo cisplatin chemotherapy display elevated c-myc expression. Br J Cancer. 1996;73(5):610-614.

    Not in our library10.1038/bjc.1996.105

48. 48.

    Yamashita H., Kobayashi S., Iwase H., Itoh Y., Kuzushima T., Iwata H., Itoh K., Naito A., Yamashita T., Masaoka A. Analysis of oncogenes and tumor suppressor genes in human breast cancer. Jpn J Cancer Res. 1993;84(8):871-878.

    Not in our library10.1111/j.1349-7006.1993.tb02060.x

49. 49.

    Zhou D. J., Ahuja H., Cline M. J. Proto-oncogene abnormalities in human breast cancer: c-ERBB-2 amplification does not correlate with recurrence of disease. Oncogene. 1989;4(1):105-108.

    Not in our library

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