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Breast Cancer

Overexpression of erb B2 remains a major risk factor in non-metastatic breast cancers treated with high-dose alkylating agents and autologous stem cell transplantation

Bone Marrow Transplantation volume 29, pages 753–757 (2002)Cite this article

Abstract

The importance of dose intensity has been strongly emphasized in high-risk breast cancer. Overexpression of erb B2 is clearly correlated with an overall poor prognosis which could be limited in patients receiving intensive chemotherapy with alkylating agents and autologous stem cell transplants (SST). Thirty-five patients with high-risk non-metastatic breast cancer (>4 involved lymph nodes), treated with high-dose chemotherapy (HDC) followed by SST were analyzed. All were previously treated by four cycles of standard-dose anthracycline or anthracene dione. Nine had erb B2 overexpression. Minimum follow-up duration was 41 months (median 68 months). At 5 years, the actuarial relapse-free survival is 57.4% and actuarial overall survival 67.4%. Patients with overexpression of erb B2 had significantly lower disease-free survivals (P: 0.021) and overall survivals (P: 0.001). On multivariate analysis, erb B2 overexpression appeared to be the single independent poor prognosis factor for relapse (RR 3.25, range 1.12 to 9.45) and overall (RR 5.28, range 1.74 to 16.03) survival. These results suggest that poor prognosis of erb B2 overexpression is unchanged after HDC with alkylating agents but a possible benefit may exist in these patients with the additional monoclonal antibody, herceptin.

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References

  1. Jacquemier J, Moles JP, Penault-Lorca F et al. P53 immunohistochemical analysis in breast cancer with four monoclonal antibodies, comparison of staining and PCR-SSCP results Br J Cancer 1994 69: 846 852

    Article  CAS  Google Scholar 

  2. Paik S, Bryant J, Park C et al. ErbB-2 and response to doxorubicin in patients with axillary lymph node-positive, hormone receptor-negative breast cancer J Natl Cancer Inst 1998 90: 1361 1370

    Article  CAS  Google Scholar 

  3. Paik S, Bryant J, Tan-Chiu E et al. Her2 and choice of adjuvant chemotherapy for invasive breast cancer: national surgical adjuvant breast and bowel project protocol b-15 J Natl Cancer Inst 2000 92: 1991 1998

    Article  CAS  Google Scholar 

  4. Slamon DJ, Godolphin W, Jones LA et al. Studies of the HER-2/neu proto-oncogene in human breast and ovarian cancer Science 1989 244: 707 712

    Article  CAS  Google Scholar 

  5. Muss HB, Thor AD, Berry D et al. C-erbB-2 expression and response to adjuvant therapy in women with node-positive early breast cancer New Engl J Med 1994 330: 1260 1266

    Article  CAS  Google Scholar 

  6. Nieto Y, Nawaz S, Jones RB et al. Prognostic model for relapse after high dose chemotherapy with autologous stem cell transplantation for stage IV oligometastatic breast cancer J Clin Oncol 2002 20: 707 718

    Article  CAS  Google Scholar 

  7. Fountzilas G, Polichronis A, Katsohis K et al. Cyclophosphamide, mitoxantrone, fluorouracil versus conventional CMF as adjuvant treatment in node-positive breast cancer patients. A Hellenic Cooperative Oncology Group Study Oncology 1996 53: 137 146

    Article  CAS  Google Scholar 

  8. Williams SF, Mick R, Desser R et al. High dose consolidation therapy with autologous stem cell rescue in stage IV breast cancer J Clin Oncol 1989 7: 1824 1830

    Article  CAS  Google Scholar 

  9. Richard B, Launay-Iliadis MC, Iliadis A et al. Pharmacokinetics of mitoxantrone in cancer patients treated by high-dose chemotherapy and autologous bone marrow transplantation Br J Cancer 1992 65: 399 404

    Article  CAS  Google Scholar 

  10. Penault-Llorca F, Adelaide J, Houvenaeghel G et al. Optimization of immunohistochemical detection of ERB B2 in human breast cancer: impact of fixation J Pathol 1994 173: 65 75

    Article  CAS  Google Scholar 

  11. Kaplan EL, Meier P . Non-parametric estimation from incomplete observations J Am Stat Assoc 1958 53: 457 481

    Article  Google Scholar 

  12. Cox DR . Statistical significance tests Br J Clin Pharmacol 1982 14: 325 331

    Article  CAS  Google Scholar 

  13. Hortobagyi GN, Buzdar AU, Theriault RL et al. Randomized trial of high-dose chemotherapy and blood cell autografts for high-risk primary breast carcinoma J Natl Cancer Inst 2000 92: 225 233

    Article  CAS  Google Scholar 

  14. Rodenhuis S, Richel DJ, Van der Wall E et al. Randomized trial of high-dose chemotherapy and haemopoietic progenitor-cell support in operable breast cancer with extensive axillary lymph-node involvement Lancet 1998 352: 515 521

    Article  CAS  Google Scholar 

  15. Bergh J, Wiklund T, Erikstein B et al. Tailored fluorouracil, epirubicin, and cyclophosphamide compared with marrow-supported high-dose chemotherapy as adjuvant treatment for high-risk breast cancer: a randomised trial Lancet 2000 356: 1384 1391

    Article  CAS  Google Scholar 

  16. Peters WP . A prospective, randomized comparison of two doses of combination alkylating agents (AA) as consolidation after CAF in high-risk primary breast cancer involving ten or more axillary lymph nodes (LN): preliminary results of CALGB 9082/SWOG 9114/NCIC MA-13 ASCO's 35th Annual Meeting, Atlanta, GA, May 15–18 1999

    Google Scholar 

  17. Thor AD, Berry DA, Budman DR et al. ErbB-2, p53, and efficacy of adjuvant therapy in lymph node-positive breast cancer J Natl Cancer Inst 1998 90: 1346 1360

    Article  CAS  Google Scholar 

  18. Bitran JD, Samuels B, Trujillo Y et al. Her2/neu overexpression is associated with treatment failure in women with high-risk stage II and stage IIIA 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 1513

    CAS  PubMed  Google Scholar 

  19. Nieto Y, Cagnoni P, Shpall E et al. A predictive model for relapse in high-risk primary breast cancer patients treated with high-dose chemotherapy and autologous stem-cell transplant Clin Cancer Res 1999 5: 3425 3431

    CAS  Google Scholar 

  20. Hengstler JG, Lange J, Kett A et al. Contribution of c-erbB-2 and topoisomerase IIalpha to chemoresistance in ovarian cancer Cancer Res 1999 59: 3206 3214

    CAS  PubMed  Google Scholar 

  21. Pegram MD, Lopez A, Konecny G, Slamon DJ . Trastuzumab and chemotherapeutics: drug interactions and synergies Semin Oncol 2000 27 (6 Suppl. 11): 21 25

    Google Scholar 

  22. Cobleigh M, Vogel CL, Tripathy D et al. Multinational study of the efficacy and safety of humanized anti-HER2 monoclonal antibody in women who have HER2-overexpressing metastatic breast cancer that has progressed after chemotherapy for metastatic disease J Clin Oncol 1999 17: 2639 2648

    Article  CAS  Google Scholar 

  23. Slamon DJ, Leyland-Jones B, Shak S et al. Use of chemotherapy plus a monoclonal antibody against HER2 for metastatic breast cancer that overexpresses HER2 New Engl J Med 2001 344: 783 792

    Article  CAS  Google Scholar 

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Authors and Affiliations

  1. Department of Medicine, Institut Paoli-Calmettes, Marseille, France

    AC Braud, VJ Bardou, G Gravis, J Camerlo, M Begue, D Maraninchi & P Viens

  2. Department of Anatomo Pathology, Institut Paoli-Calmettes, Marseille, France

    MP Mathoulin Portier & J Jacquemier

  3. Department of Surgery, Institut Paoli-Calmettes, Marseille, France

    G Houvenaeghel

  4. Université de la Méditerranée, Marseille, France

    F Bertucci

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  1. AC Braud
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Braud, A., Mathoulin Portier, M., Bardou, V. et al. Overexpression of erb B2 remains a major risk factor in non-metastatic breast cancers treated with high-dose alkylating agents and autologous stem cell transplantation. Bone Marrow Transplant 29, 753–757 (2002). https://doi.org/10.1038/sj.bmt.1703540

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