The Correlation between HER-2/neu Overexpression and Prognostic and Predictive Factor in Primary Breast Cancer
Keywords:
Breast Cancer, HER-2/neu/c-erb B2, Estrogen Receptor, Progesterone Receptor, Immunohistochemistry (IHC)Abstract
Background: An over-expression of HER-2/neu protein has been reported to be associated with a poor clinical outcome in breast cancer. However, its prognostic value is important, especially in patients with node status, and in relation to the estrogen receptor (ER) and progesterone receptor (PR) status.
Objectives: To determine the correlation between HER-2/neu expression and several known, well- accepted prognostic indicators of invasive breast carcinoma.
Materials and Methods: This study analyzed data from 251 women with primary invasive breast cancer at Rajavithi Hospital (tertiary care hospital of Ministry of Public Health), Bangkok, Thailand. The pathological detection of Iymph node metastasis and the detection of HER-2/neu protein, estrogen and progesterone receptor expression were performed using immunochemistry.
Results: Twenty-five percent of patients (61/251) showed HER.2/neu over-expression. HER-2/neu- positive tumors were not correlated with age and number of positive nodes (p value = 0.544 and 0.272, respectively) but there was an association between HER. 2/neu-positive tumors and estrogen-negative tumors and progesterone-negative tumors (p value = 0.031 and 0.022, respectively).
Conclusion: There was good correlation between HER-2/neu expression and several known, well. accepted prognostic indicators of invasive breast carcinoma such as nodal status, estrogen receptor status and progesterone receptor status.
References
1. Fukushige S, Matsubara K, Yoshida M, et al. Localization of a novel v-erbB-related gene, c-erbB-2, on human chromosome 17 and its amplification in a gastric cancer cell line. Mol Cell Biol 1986; 6: 955-8.
2. Coussens L, Yang-Feng TL, Liao YC, rt al. Tyrosine kinase receptor with extensive homology to EGF receptor shares chromosomal location with neu oncogene. Science 1985; 230(4730): 1132-9.
3. Schechter AL, Stern DF, Vaidyanathan L, et al. The neuoncogene: an erb-B-related gene encoding a 185,000-Mr tumour antigen. Nature 1984;312(5994): 513-6
4. Yamamoto T, Ikawa S, Akiyama T, et al. Similarity of protein encoded by the human c-erb-B-2 gene to epidermal growth factor receptor. Nature 1986; 319(6050): 230-4.
5. Pegram M, Slamon D. Biological rationale for HER2/neu (c-erbB2) as a target for monoclonal antibody therapy. Semin Oncol 2000; 27 (Suppl 9): 13-9.
6. Wang SC, Zhang L, Hortobagyi GN, Hung MC. Targeting HER2: recent developments and future directions for breast cancer patients. Semin Oncol 2001; 28 (Suppl 18): 21-9
7. Cobleigh MA, Vogel CL, Tripathy D, et al. Efficacy and safety of Herceptin (humanized anti-HER2 antibody) as a single agent in 222 women with HER2 overexpression who relapsed following chemotherapy for metastatic breast cancer. Proc Am Soc Clin Oncol 1998; 17: 97A.
8. Slamon D, Leyland-Jones B, Shak S, et al. Addition of Herceptin (humanized anti-HER2 antibody) to first line chemotherapy for HER2 overexpressing metastatic breast cancer (HER+/MBC) markedly increases anticancer activity: A randomized, multinational controlled phase lll trial. Proc Am Soc Clin Oncol 1998; 17: 98a.
9. Pegram MD, Lipton A, Hayes DF, et al. Phase ll study of receptor-enhanced chemosensitivity using recombinant humanized anti-p185HER2/neu monoclonal antibody plus cisplatin in patients with HER2 /neu-overexpressing metastatic breast cancer refractory to chemotherapy treatment, J Clin Oncol 1998; 16: 2659-71.
10. Slamon DJ, Godolphin W, Jones LA, et al. Studies of the HER-2/neuproto-oncogene in human breast and ovarian cancer. Science 1989; 244(4905): 707-12
11. Slamon DJ, Clark GM, Wong SG, et al. Human breast cancer: correlation of relapse and survival with amplification of the HER-2/neu oncogene. Science 1987; 235:177-82.
12. Revillion F, Bonneterre J, Peyrat JP. ERBB2 oncogene in human breast cancer and its clinical significance, Eur J Cancer 1998; 34:791-808.
13. Tsutsui S, Ohno S, Murakami S, Hachitanda Y, Oda S. Prognostic value of c-erbB2 expression in breast cancer. J Surg Oncol 2002; 79: 216-23.
14. Hanna W, Kahn HJ, Trudeau M. Evaluation of HER-2/neu (erbB-2) status in breast cancer: from bench to bedside. Mod Pathol 1999; 12: 827-34.
15. Quenel N, Wafflart J, Bonichon F, et al. The prognostic value of c-erbB2 in primary breast carcinomas; a study on 942 cases. Breast Cancer Res Treat 1995; 35: 283-91.
16. Press MF, Bernstein L, Thomas PA, et al. HER-2/neu gene amplification characterized by fluorescence in
situ hybridization; poor prognosis in node-negative breast carcinomas. J Clin Oncol 1997:15: 2894-904.
17. Orvieto E, Dei Tos AP. Measurement of HER-2/neu in breast cancer. which methodologic approach? Pathologica 2001; 93:183-8
18. Tetu B, Brisson J, Plante V, et al. p53 and c-erbB-2 as markers of resistance to adjuvant chemotherapy in breast cancer. Mod Pathol 1998; 11: 823-30.
19. Stal O, Sullivan S, Wingren S, et al. c-erbB-2 expression and benefit from adjuvant chemotherapy and radiotherapy of breast cancer. Eur J Cancer 1995: 31A: 2185-90.
20. Bitran JD, Samuels B, Trujillo Y, et al. Her2/ neu overexpression is associated with treatment failure in women with high-risk stage ll and stage IIA breast cancer (> 10 involved lymph nodes) treated with high-dose chemotherapy and autologous hematopoietic progenitor cell support following standard-dose adjuvant chemotherapy. Clin Cancer Res 1996; 2: 1509-13.
21. Berns EM, Foekens JA, van Staveren IL, et al. Oncogene amplification and prognosis in breast cancer: relationship with systemic treatment. Gene 1995; 159: 11-8.
22. Carlomagno C, Perrone F, Gallo C, et al, c-erb B2 overexpression decreases the benefit of adjuvant tamoxifen in early-stage breast cancer without axillary lymph node metastases. J Clin Oncol 1996;14: 2702-8.
23. Sjogren S, Inganas M, Lindgren A, et al. Prognostic and predictive value of c-erbB-2 overexpression in primary breast cancer, alone and in combination with other prognostic markers. J Clin Oncol 1998; 16: 462-9.
24. Jacobs TW, Gown AM, Yaziji H, Barnes MJ, Schnitt SJ. Comparison of fluorescence in situ hybridization and immunohistochemistry for the evaluation of HER-2/neu in breast cancer. J Clin Oncol 1999; 17: 1974-82.
25. Yaziji H, Goldstein LC, Barry TS, et al. HER-2 testing in breast cancer using parallel tissue-based methods. JAMA 2004;291: 1972-7.
26. Sampatanukul P, Wannakrairot P, Thanakit V, et al. Immunohistochemical detections of ER, PR and HER2 status of invasive mammary carcinoma: a synopsis on current staining protocol, interpretation criteria and quality control measures by the breast pathology group. J R C Pathol Thai 2003;2:112-7.
27. Thomson TA, Hayes MM, Spinelli JJ, et al. HER-2/neu in breast cancer: interobserver variability and performance of immunohistochemistry with 4 antibodies compared with fluorescent in situ hybridization, Mod Pathol 2001; 14: 1079-86.
28. S Selvarajan, BH Bay, MJ Chng, PH Tan. The HercepTest and Routine C-erbB2 Immunohistochemistry in breast cancer: any difference? Ann Acad Med Singapore 2004; 33: 473-6
29. Jacobs TW, Gown AM, Yaziji H, Barnes MJ, Schnitt SJ. HER-2/ neu protein expression in breast cancer evaluated by immunohistochemistry. A study of interlaboratory agreement. Am J Clin Pathol 2000; 113: 251-8.
30. Chen Y, Dong J, Lu Y, McGee JO. Quantitative detection of amplification of proto-oncogenes in breast cancer. Chin Med J (Engl) 1995; 108: 849-54.
31. Valeron PF, Chirino R, Fernandez L, et al. Validation of a differential PCR and an ELISA procedure in studying HER-2/neu status in breast cancer. Int J Cancer 1996;65:129-33.
32. Looi LM, Cheah PL, Yap SF. Correlation between histological grade and c-erbB2 oncoprotein overexpression in infiltrating ductal carcinoma of breast. Malays J Pathol 1997;19: 35-9.
33. el-A Helal T, Khalifa A, Kamel AS, Immunohistochemical expression of p53 and c-erbB2 proteins in breast cancer in Egypt. Anticancer Res 2000; 20(3B): 2145-50.
34. DiGiovanna MP, Stern DF, Edgerton SM, et al. Relationship of epidermal growth factor expression to ErbB-2 signaling activity and prognosis in breast cancer patients. J Clin Oncol 2005;23: 1152-60.
2. Coussens L, Yang-Feng TL, Liao YC, rt al. Tyrosine kinase receptor with extensive homology to EGF receptor shares chromosomal location with neu oncogene. Science 1985; 230(4730): 1132-9.
3. Schechter AL, Stern DF, Vaidyanathan L, et al. The neuoncogene: an erb-B-related gene encoding a 185,000-Mr tumour antigen. Nature 1984;312(5994): 513-6
4. Yamamoto T, Ikawa S, Akiyama T, et al. Similarity of protein encoded by the human c-erb-B-2 gene to epidermal growth factor receptor. Nature 1986; 319(6050): 230-4.
5. Pegram M, Slamon D. Biological rationale for HER2/neu (c-erbB2) as a target for monoclonal antibody therapy. Semin Oncol 2000; 27 (Suppl 9): 13-9.
6. Wang SC, Zhang L, Hortobagyi GN, Hung MC. Targeting HER2: recent developments and future directions for breast cancer patients. Semin Oncol 2001; 28 (Suppl 18): 21-9
7. Cobleigh MA, Vogel CL, Tripathy D, et al. Efficacy and safety of Herceptin (humanized anti-HER2 antibody) as a single agent in 222 women with HER2 overexpression who relapsed following chemotherapy for metastatic breast cancer. Proc Am Soc Clin Oncol 1998; 17: 97A.
8. Slamon D, Leyland-Jones B, Shak S, et al. Addition of Herceptin (humanized anti-HER2 antibody) to first line chemotherapy for HER2 overexpressing metastatic breast cancer (HER+/MBC) markedly increases anticancer activity: A randomized, multinational controlled phase lll trial. Proc Am Soc Clin Oncol 1998; 17: 98a.
9. Pegram MD, Lipton A, Hayes DF, et al. Phase ll study of receptor-enhanced chemosensitivity using recombinant humanized anti-p185HER2/neu monoclonal antibody plus cisplatin in patients with HER2 /neu-overexpressing metastatic breast cancer refractory to chemotherapy treatment, J Clin Oncol 1998; 16: 2659-71.
10. Slamon DJ, Godolphin W, Jones LA, et al. Studies of the HER-2/neuproto-oncogene in human breast and ovarian cancer. Science 1989; 244(4905): 707-12
11. Slamon DJ, Clark GM, Wong SG, et al. Human breast cancer: correlation of relapse and survival with amplification of the HER-2/neu oncogene. Science 1987; 235:177-82.
12. Revillion F, Bonneterre J, Peyrat JP. ERBB2 oncogene in human breast cancer and its clinical significance, Eur J Cancer 1998; 34:791-808.
13. Tsutsui S, Ohno S, Murakami S, Hachitanda Y, Oda S. Prognostic value of c-erbB2 expression in breast cancer. J Surg Oncol 2002; 79: 216-23.
14. Hanna W, Kahn HJ, Trudeau M. Evaluation of HER-2/neu (erbB-2) status in breast cancer: from bench to bedside. Mod Pathol 1999; 12: 827-34.
15. Quenel N, Wafflart J, Bonichon F, et al. The prognostic value of c-erbB2 in primary breast carcinomas; a study on 942 cases. Breast Cancer Res Treat 1995; 35: 283-91.
16. Press MF, Bernstein L, Thomas PA, et al. HER-2/neu gene amplification characterized by fluorescence in
situ hybridization; poor prognosis in node-negative breast carcinomas. J Clin Oncol 1997:15: 2894-904.
17. Orvieto E, Dei Tos AP. Measurement of HER-2/neu in breast cancer. which methodologic approach? Pathologica 2001; 93:183-8
18. Tetu B, Brisson J, Plante V, et al. p53 and c-erbB-2 as markers of resistance to adjuvant chemotherapy in breast cancer. Mod Pathol 1998; 11: 823-30.
19. Stal O, Sullivan S, Wingren S, et al. c-erbB-2 expression and benefit from adjuvant chemotherapy and radiotherapy of breast cancer. Eur J Cancer 1995: 31A: 2185-90.
20. Bitran JD, Samuels B, Trujillo Y, et al. Her2/ neu overexpression is associated with treatment failure in women with high-risk stage ll and stage IIA breast cancer (> 10 involved lymph nodes) treated with high-dose chemotherapy and autologous hematopoietic progenitor cell support following standard-dose adjuvant chemotherapy. Clin Cancer Res 1996; 2: 1509-13.
21. Berns EM, Foekens JA, van Staveren IL, et al. Oncogene amplification and prognosis in breast cancer: relationship with systemic treatment. Gene 1995; 159: 11-8.
22. Carlomagno C, Perrone F, Gallo C, et al, c-erb B2 overexpression decreases the benefit of adjuvant tamoxifen in early-stage breast cancer without axillary lymph node metastases. J Clin Oncol 1996;14: 2702-8.
23. Sjogren S, Inganas M, Lindgren A, et al. Prognostic and predictive value of c-erbB-2 overexpression in primary breast cancer, alone and in combination with other prognostic markers. J Clin Oncol 1998; 16: 462-9.
24. Jacobs TW, Gown AM, Yaziji H, Barnes MJ, Schnitt SJ. Comparison of fluorescence in situ hybridization and immunohistochemistry for the evaluation of HER-2/neu in breast cancer. J Clin Oncol 1999; 17: 1974-82.
25. Yaziji H, Goldstein LC, Barry TS, et al. HER-2 testing in breast cancer using parallel tissue-based methods. JAMA 2004;291: 1972-7.
26. Sampatanukul P, Wannakrairot P, Thanakit V, et al. Immunohistochemical detections of ER, PR and HER2 status of invasive mammary carcinoma: a synopsis on current staining protocol, interpretation criteria and quality control measures by the breast pathology group. J R C Pathol Thai 2003;2:112-7.
27. Thomson TA, Hayes MM, Spinelli JJ, et al. HER-2/neu in breast cancer: interobserver variability and performance of immunohistochemistry with 4 antibodies compared with fluorescent in situ hybridization, Mod Pathol 2001; 14: 1079-86.
28. S Selvarajan, BH Bay, MJ Chng, PH Tan. The HercepTest and Routine C-erbB2 Immunohistochemistry in breast cancer: any difference? Ann Acad Med Singapore 2004; 33: 473-6
29. Jacobs TW, Gown AM, Yaziji H, Barnes MJ, Schnitt SJ. HER-2/ neu protein expression in breast cancer evaluated by immunohistochemistry. A study of interlaboratory agreement. Am J Clin Pathol 2000; 113: 251-8.
30. Chen Y, Dong J, Lu Y, McGee JO. Quantitative detection of amplification of proto-oncogenes in breast cancer. Chin Med J (Engl) 1995; 108: 849-54.
31. Valeron PF, Chirino R, Fernandez L, et al. Validation of a differential PCR and an ELISA procedure in studying HER-2/neu status in breast cancer. Int J Cancer 1996;65:129-33.
32. Looi LM, Cheah PL, Yap SF. Correlation between histological grade and c-erbB2 oncoprotein overexpression in infiltrating ductal carcinoma of breast. Malays J Pathol 1997;19: 35-9.
33. el-A Helal T, Khalifa A, Kamel AS, Immunohistochemical expression of p53 and c-erbB2 proteins in breast cancer in Egypt. Anticancer Res 2000; 20(3B): 2145-50.
34. DiGiovanna MP, Stern DF, Edgerton SM, et al. Relationship of epidermal growth factor expression to ErbB-2 signaling activity and prognosis in breast cancer patients. J Clin Oncol 2005;23: 1152-60.
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Published
2005-06-30
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Kuntanapreeda K, Komindr A, Mahatharadol V. The Correlation between HER-2/neu Overexpression and Prognostic and Predictive Factor in Primary Breast Cancer. Thai J Surg [Internet]. 2005 Jun. 30 [cited 2024 Nov. 23];26(2):43-9. Available from: https://he02.tci-thaijo.org/index.php/ThaiJSurg/article/view/242144
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