medigraphic.com
ISSN 0016-3813 (Print)

2002, Number 1

<< Back Next >>

Gac Med Mex 2002; 138 (1)

Biomarkers on Prognosis and Response to Treatment in Breast Cancer.

Gerson R, Serrano A, Villalobos A, Sánchez-Forgach E, Sánchez BC, Murillo A, Ortiz-Hidalgo C

Language: Spanish
References: 57
Page: 15-24
PDF size: 85.49 Kb.


ABSTRACT

Purpose: To determine the prognostic value of c-erbB-2, p53, hormone receptors and angiogenesis, on recurrence free time and its relationship to treatment in breast cancer patients. Methods: Women with histologic diagnosis of breast cancer and immunohistochemical determination of biologic factors. Clinic, histologic, molecular factors and recurrence free time were registered. Results: 101 patients, ages 51.98 ± 11.5 years. Follow-up 32.52 ± 24.3 months. Tumor recurred in 31, (30.69%); 15 (48.33%) had tumor size above 2.1cm, 19 (61.29%) showed positive estrogen receptors and 18 (58.07%) for progesterone; 20 (64.51 %) to c-erbB-2 expression (64.51%); 18 to p53; average microvessels 24.48 ± 17.27. Tumor size related to recurrence, p = 0.008. Kruskal-Wallis test did not show a difference when correlating survival free time and biologic factors. 24 pts. (77.41%) received hormones; 20 (64.5%) chemotherapy (61.29%); 19 (61.29%) radiotherapy. Response prediction to hormones with estrogen receptor positive, p = 0.059; to chemotherapy in angiogenesis under 40 vessels/field = 0.024. Conclusions: Tumor size has prognostic implications. A clear positive tendency was observed with p53 and higher microvessel density. Estrogen receptors offer predictive response value to hormone treatment and lower vascular density to chemotherapy, treatment indicators of possible therapeutic association.


REFERENCES

  1. Registro Histopatológico de Neoplasias en México. Departamento de Epidemiología de la Secretaría de Salud.1996.

  2. Harris JR, Lippman ME, Veronesi U, et al. Breast Cancer. N Engl J Med 1992;327:319-328.

  3. Smith BL. Approaches to breast cancer staging. N Engl J Med 2000;342:580-81.

  4. Heimann R, Ferguson D, Recant WM, et al. Predicción del fenotipo metastático del cáncer mamario con los marcadores histológicos tumorales. Cancer J Sci 1997;3:224-29.

  5. van der Vijver MJ, Petersen JL, Mooi WJ, et al. Neu-Protein overexpression in breast cancer association between comedo-type ductal carcinoma in situ and limited prognostic value, in stage II breast cancer. N Engl J Med 1988;319:1239-45.

  6. Gasparini G, Gullick WJ, Bevilarqua P, et al. Human breast cancer: prognostic significance of the c-erbB-2 oncoprotein expression compared with epidermal growth factor receptor DNA policy and conventional pathologic features. J Clin Oncol 1992;10(5):686-95.

  7. King CR, Kraus MH, Aaronson SA. Amplification of a novel c-erbB-2 related gene in a human mammary carcinoma. Science 1985;229:974-76.

  8. Hall P. p53: The challenge of linking basic science and patient management. The Oncologist 1999;3:218.

  9. Kastan MB. p53 and ATM: Tumor supressor genes that have an impact on therapeutic responses. Sem Oncol 1997:53.

  10. Pudla JM. Tumor associated angiogenesis: mechanisms, clinical implications, and the therapeutic strategies. Sem Oncol 1997;24(2):203-18.

  11. Klagsbrun M, Amore PA. Regulators of angiogenesis. Ann RevPhysiol 1991;53:217-39.

  12. Weidner L. The relationship of tumor angiogenesis and metastasis with emphasis on invasive breast carcinoma. Advances in Pathology and Laboratory Medicine, vol. 5 1992,101-21.

  13. Watson JC, Redmann JG, Meyers MO, et al. Breast cancer increases initiation of angiogenesis without accelerating neovessel growth rate. Surgery 1997;122: 508-13.

  14. Ross JS, Fletcher JA. The HER-2neu oncogen in breast cancer: Prognostic factor, predictive factor and target for therapy. The Oncologist 1998;3:237.

  15. Sahin AA, Valero V. Prognostic factors for invasive breast cancer. In: Breast Cancer. Ed. Eva Singletary. Springer, New York, 1999:93-119.

  16. Baselga J, Seidman A, Rosen PP. HER2 overexpression and paclitaxel sensitivity in breast cancer: therapeutic implications, Oncology 1997;11(supl 2):43.

  17. Gasparini G, Weidner N, Bevilacqua P, et al. Tumor microvessel density, p53 expression, tumor size, and peritumoral lymphatic vessel invasion are relevant prognostic markers in node negative breast carcinoma. J Clin Oncol 1994;12:454.

  18. Weiss MC, Kelsten. Biologic markers of breast cancer prognosis. In: Breast cancer treatment. A comprehensive guide to management. Ed. Fowble B, Goodman R. Mosby Yearbook, Saint Louis Mo. 1991.

  19. Slamon DJ, Clark GM. Amplification of c-erbB-2 and aggresive human breast tumors. Science 1988;240:1795-1798.

  20. Ravdin PM. Prognostic factors in breast cancer. Educational Book, ASCO 1997;217-27.

  21. Seshadri R, Firgaira FA, Horsfall DJ, et al. Clinical significance of HER-2/neu oncogene amplification in primary breast cancer. J Clin Oncol 1993; 11(10): 1936-1942.

  22. Felipe E, Del Campo JM, Rubio D, et al. Overexpression of c-erbB-2 in epithelial ovarian cancer. Prognostic value and relationship with response to chemotherapy. Cancer 1995;75:2147-52.

  23. Ravdin PM, Green S, Melink-dorr T. Prognostic significance of progesteron receptor levels in estrogen receptor positive in patients with metastatic breast cancer treated with tamoxifen J Clin oncol 1992;10:1284.

  24. Leitzel K, Teramoto Y, Konrad K, et al. Elevated serum c-erbB-2 antigen levels and decreased response to hormone therapy of breast cancer. J Clin Oncol 1995;13:1129.

  25. Yamauchi H, O’Neill A, Gelman R, et al. Prediction of response to antiestrogen therapy in advanced breast cancer patients by pretreatment circulating levels of extracellular domain of the HER-2/C-neu protein. J Clin Oncol 1997;15:2518.

  26. Cobleigh MA, Vogel CL, Tripathy D, et al. Efficacy and safety of Herceptin (Humanized anti-her-2 antibody) as a single agent in 222 women with HER-2 overexpression who relapsed following chemotherapy for metastatic breast cancer. Proc ASCO 1998;97a:376.

  27. Siamon D, Jones L, Shak S, et al. Addition of herceptin (Humanized anti-HER-2 antibody) to first line chemotherapy for HER-2 overexpressing metastatic breast cancer) markedly increases anticancer activity. Proc ASCO 1998;98a:377.

  28. Nigro JM, Baker JS, Preisinger, et al. Mutations in the p53 gene occur in diverse human tumor types. Nature 1989;342:105.

  29. Gasparini G, Toi M, Gion M, et al. Prognostic significance of vascular endothelial growth factor protein in node negative breast cancer. J Natl Cancer lnst 1997;89:139.

  30. Nigro JM, Baker JS, Preisinger, et al. Mutations in the p53 gene occur in diverse human tumor types. Nature 1989;342:105.

  31. Phillips A. NK, Ozcelik H, et al. Frequency of p53 mutations in breast carcinoma from ashkenazi jewish carriers of BRCA-1 mutations. J Natl Cancer Inst 1999;91:469.

  32. Mackay HJ, Cameron D, Rahilly M, et al. Reduced MLHI expression in breast tumors after primary chemotherapy predicts disease free survival. J Clin Oncol 2000;18:87.

  33. Dameron KM, Volpert 0V, Tainsky MA, et al. Control of angiogenesis in fibroblasts by p53 regulation of thrompospondin-1. Science 1994;265:1582-85.

  34. Insa A, Lluch A, Prosper F, et al. Prognostic factors predicting survival from first recurrence in patients with metastatic breast cancer: analysis of 439 patients. Breast Cancer Research and Treatment 1999;67.

  35. Barbi GP, Marroni P, Bruzzi F, et al. Correlation between steroid hormone receptors and prognostic factors in human breast cancer. Oncology 1987;44:265.

  36. Shingakowinta A, Potter HG, Buroker TR, et al. Estrogen receptor and the natural course of breast cancer. Ann Surg 1976;183:184.

  37. Mason BH, Holdaway IM, Nullins PR, et al. Progesteron and estrogen receptors as prognostic variables in breast cancer. Cancer Research 1983;43:2985-90.

  38. Allegra J, Lippman M, Simon R, et al. Association between steroid hormone receptor status and disease free survival interval in breast cancer. Cancer Treat Rep 1979;63:1271-77.

  39. Kinne DW, Ashikari R, Butler A, et al. Estrogen receptor protein in breast cancer as a predictor of recurrence. Cancer 1981;47:2364.

  40. Robertson JRF, Cannon PM, Nicholson Rl, et al. Oestrogen and progesteron receptors as prognostic variables in hormonally treated breast cancer. International J Biological Markers 1996;11:29.

  41. Pichon MF, Broet P, Magdelenat H, et al. Prognostic value of steroid receptors after long term follow-up of 2257 operable breast cancers. Br J Cancer 1996;73: 1545.

  42. Arteaga CL, Koli KM, Dugger TC, et al. Reversal of tamoxifen resistance of human breast carcinomas in vivo by neutralizing antibodies to transforming growth factor-beta. J Natl Cancer lnst 1999;91:46.

  43. Horak E, Leek R, Klenk N, et al. Angiogenesis assessed by platelet 1 endothelial cell adhesion molecule antibodies, as indicator of node metastases and survival in breast cancer. Lancet 1992;340:1120-24.

  44. Gerson R, Serrano A, Villalobos A, et al. Angiogenesis in breast cancer. Proc ASCO 1999;629a:2433.

  45. Van Hoef MEHM, Knox WF, Dhesi SS, et al. Assessment of tumor vascularity as a prognostic factor in lymph node negative invasive breast cancer. Eur J Cancer 1993;29A:1141-45.

  46. Hall NR, Fish DE, Hunt N, et al. Is the relationship between angiogenesis and metastasis in breast cancer real? Surg Oncol 1992;1:223-29.

  47. Heimann R, Ferguson D, Powers C, et al. Angiogenesis as a predictor of long-term survival for patients wit node-negative breast cancer. J Natl Cancer lnst 1996;88:1764-9.

  48. Guinebretiere JM, Monique GL, Gavoille A, et al. Angiogenesis and risk of breast cancer in women with fibrocystic disease. J Natl Cancer lnst 1994;86(8):635.

  49. Ellis LM, Fidler IJ. Angiogenesis and breast cancer metastasis. The Lancet 1995;346:388-90.

  50. Harris AL, Fox S, Leek R, et al. Breast cancer angiogenesis: Therapy target and prognostic factor. Eur J Cancer 1995;31A(5):831-32.

  51. Eckhardt SG, Pluda JM. Development of angiogenesis inhibitors for cancer therapy. lnvest New Drugs 1997;15:1-3.

  52. Locopo N, Fanelli M, Gasparini G. Clinical significance of angiogenic factors in breast cancer. Breast Cancer Res Treat 1998;52:159-73.

  53. Balsan A, Maier JA, Colnaghi Ml, Menard S. Correlation between tumoral vascularity, vascular endothelial growth factor production by tumor cells, serum vascular endothelial growth factor levels, and serum angiogenic activity in patients with breast carcinoma. Lab lnvest 1999;79:897-902.

  54. Heimann R, Ferguson D, Gray S, Hellman S. Assessment of intratumoral vascularization (angiogenesis) in breast cancer prognosis. Breast Cancer Res Treat 1998;52:147-58.

  55. Quiet CA, Ferguson DJ, Weichselbaum RR, et al. Natural history of node negative breast cancer: A study of 826 patients with long term follow-up. J Clin Oncol 1995;13:1144.

  56. Quiet CA, Ferguson DJ, Wichselbaum RR, et al. Natural history of breast cancer; the curability of small cancers with a limited number of positive nodes. J Clin Oncol 1996;14:3105.

  57. Heimann R, Helíman S. Clinical progression of breast cancer malignant behaviour : what to expect and when to expect it. J Clin Oncol; 2000;18:591-599.




2020     |     www.medigraphic.com