This Article Full Text Full Text (PDF) Purchase Article View Shopping Cart Alert me when this article is cited Alert me if a correction is posted Services Email this article to a colleague Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Save to my personal folders Download to citation manager Rights & Permissions Citing Articles Citing Articles via HighWire Citing Articles via Google Scholar Google Scholar Articles by Nieto, Y. Articles by Jones, R. B. Search for Related Content PubMed PubMed Citation Articles by Nieto, Y. Articles by Jones, R. B. Social Bookmarking                            What's this?

Evaluation of the Predictive Value of Her-2/neu Overexpression and p53 Mutations in High-Risk Primary Breast Cancer Patients Treated With High-Dose Chemotherapy and Autologous Stem-Cell Transplantation

From the University of Colorado Bone Marrow Transplant Program and Departments of Pathology and Biostatistics, University of Colorado, Denver, CO.

Address reprint requests to Yago Nieto, MD, University of Colorado Health Sciences Center, B# 190, 4200 East Ninth Avenue, Denver, CO 80262; email yago.nieto{at}uchsc.edu

PURPOSE: To ascertain the predictive value of Her-2/neu overexpression and p53 mutations, assessed by immunohistochemistry, in high-risk primary breast cancer (HRPBC) treated with high-dose chemotherapy (HDCT).

PATIENTS AND METHODS: We obtained paraffin-embedded tumor blocks from 146 HRPBC patients previously enrolled at our program onto clinical trials of HDCT for four to nine involved axillary lymph nodes, 10 involved axillary nodes, or inflammatory carcinoma. All patients received the same HDCT regimen, with cyclophosphamide, cisplatin, and carmustine (STAMP-I), followed by autologous stem-cell transplantation. Median follow-up was 42 months (range, 5 to 90 months). The same pathologist, blinded to clinical outcome, reviewed all immunostained slides.

RESULTS: Positive results for Her-2/neu and p53 were found in 44.5% and 34% of the patients, respectively. Positivity for Her-2/neu was significantly associated with increased risk of relapse and death. No correlation was found between p53 mutations and relapse-free survival (RFS) or overall survival (OS). Multivariate analyses included Her-2/neu overexpression and the following variables previously identified as independent predictors of outcome in this population: tumor size, nodal ratio (number of involved nodes/number of dissected nodes), and hormone receptor status. All four variables had independent value.

CONCLUSION: Her-2/neu overexpression is an independent negative predictor of RFS and OS in HRPBC treated with HDCT. Its inclusion in our previously described predictive model increases the predictive capacity of this model for the low-risk subgroup. In contrast, p53 mutations lack predictive value in this setting.

Presented in part at the Thirty-Fifth Annual Meeting of the American Society of Clinical Oncology, Atlanta, GA, May 15-18, 1999. Y.N. is an American Society of Clinical Oncology Merit Award recipient.

CiteULike    Complore    Connotea    Del.icio.us    Digg    Facebook    Reddit    Technorati    Twitter    What's this?

This article has been cited by other articles:

				G. Somlo, P. Chu, P. Frankel, W. Ye, S. Groshen, J. H. Doroshow, K. Danenberg, and P. Danenberg Molecular profiling including epidermal growth factor receptor and p21 expression in high-risk breast cancer patients as indicators of outcome Ann. Onc., November 1, 2008; 19(11): 1853 - 1859. [Abstract] [Full Text] [PDF]

				O. Gluz, U. A. Nitz, N. Harbeck, E. Ting, R. Kates, A. Herr, W. Lindemann, C. Jackisch, W. E. Berdel, H. Kirchner, et al. Triple-negative high-risk breast cancer derives particular benefit from dose intensification of adjuvant chemotherapy: results of WSG AM-01 trial Ann. Onc., May 1, 2008; 19(5): 861 - 870. [Abstract] [Full Text] [PDF]

				Y. Nieto, F. Nawaz, R. B. Jones, E. J. Shpall, and S. Nawaz Prognostic Significance of Overexpression and Phosphorylation of Epidermal Growth Factor Receptor (EGFR) and the Presence of Truncated EGFRvIII in Locoregionally Advanced Breast Cancer J. Clin. Oncol., October 1, 2007; 25(28): 4405 - 4413. [Abstract] [Full Text] [PDF]

				N. Kroger, K. Milde-Langosch, S. Riethdorf, C. Schmoor, M. Schumacher, A. R. Zander, and T. Loning Prognostic and Predictive Effects of Immunohistochemical Factors in High-Risk Primary Breast Cancer Patients Clin. Cancer Res., January 1, 2006; 12(1): 159 - 168. [Abstract] [Full Text] [PDF]

				A. Schneeweiss, I. Diel, M. Hensel, S. Kaul, H.-P. Sinn, K. Unnebrink, C. Rudlowski, I. Lauschner, F. Schuetz, G. Egerer, et al. Micrometastatic bone marrow cells at diagnosis have no impact on survival of primary breast cancer patients with extensive axillary lymph node involvement treated with stem cell-supported high-dose chemotherapy Ann. Onc., November 1, 2004; 15(11): 1627 - 1632. [Abstract] [Full Text] [PDF]

				Y. Nieto, J. J. Vredenburgh, E. J. Shpall, S. I. Bearman, P. A. McSweeney, N. Chao, D. Rizzieri, C. Gasparetto, S. Matthes, A. E. Baron, et al. Phase II Feasibility and Pharmacokinetic Study of Concurrent Administration of Trastuzumab and High-Dose Chemotherapy in Advanced HER2+ Breast Cancer Clin. Cancer Res., November 1, 2004; 10(21): 7136 - 7143. [Abstract] [Full Text] [PDF]

				Y. Nieto, E. J. Shpall, I. K. McNiece, S. Nawaz, J. Beaudet, S. Rosinski, J. Pellom, V. Slat-Vasquez, P. A. McSweeney, S. I. Bearman, et al. Prognostic Analysis of Early Lymphocyte Recovery in Patients with Advanced Breast Cancer Receiving High-Dose Chemotherapy with an Autologous Hematopoietic Progenitor Cell Transplant Clin. Cancer Res., August 1, 2004; 10(15): 5076 - 5086. [Abstract] [Full Text] [PDF]

				G. Somlo, P. Frankel, W. Chow, L. Leong, K. Margolin, R. Morgan Jr, S. Shibata, P. Chu, S. Forman, D. Lim, et al. Prognostic Indicators and Survival in Patients With Stage IIIB Inflammatory Breast Carcinoma After Dose-Intense Chemotherapy J. Clin. Oncol., May 15, 2004; 22(10): 1839 - 1848. [Abstract] [Full Text] [PDF]

				Y. Nieto, S. Nawaz, E. J. Shpall, S. I. Bearman, J. Murphy, and R. B. Jones Long-Term Analysis and Prospective Validation of a Prognostic Model for Patients with High-Risk Primary Breast Cancer Receiving High-Dose Chemotherapy Clin. Cancer Res., April 15, 2004; 10(8): 2609 - 2617. [Abstract] [Full Text] [PDF]

				P. J. Wild, A. Reichle, R. Andreesen, G. Rockelein, W. Dietmaier, J. Ruschoff, H. Blaszyk, F. Hofstadter, and A. Hartmann Microsatellite Instability Predicts Poor Short-Term Survival in Patients with Advanced Breast Cancer after High-Dose Chemotherapy and Autologous Stem-Cell Transplantation Clin. Cancer Res., January 15, 2004; 10(2): 556 - 564. [Abstract] [Full Text] [PDF]

				S. Rodenhuis, M. Bontenbal, L. V.A.M. Beex, J. Wagstaff, D. J. Richel, M. A. Nooij, E. E. Voest, P. Hupperets, H. van Tinteren, H. L. Peterse, et al. High-Dose Chemotherapy with Hematopoietic Stem-Cell Rescue for High-Risk Breast Cancer N. Engl. J. Med., July 3, 2003; 349(1): 7 - 16. [Abstract] [Full Text] [PDF]

				M. Hensel, A. D. Ho, G. Bastert, and A. Schneeweiss Prognostic markers for survival after high-dose chemotherapy with autologous stem-cell transplantation for breast cancer Ann. Onc., February 1, 2003; 14(2): 341 - 341. [Full Text] [PDF]

				J. Climent, J. A. Martinez-Climent, D. Blesa, M. J. Garcia-Barchino, R. Saez, D. Sanchez-Izquierdo, P. Azagra, A. Lluch, and J. Garcia-Conde Genomic Loss of 18p Predicts an Adverse Clinical Outcome in Patients with High-Risk Breast Cancer Clin. Cancer Res., December 1, 2002; 8(12): 3863 - 3869. [Abstract] [Full Text] [PDF]

				J. G. Schrama, I. F. Faneyte, J. H. Schornagel, J. W. Baars, J. L. Peterse, M. J. van de Vijver, O. Dalesio, H. van Tinteren, E. J. T. Rutgers, D. J. Richel, et al. Randomized trial of high-dose chemotherapy and hematopoietic progenitor-cell support in operable breast cancer with extensive lymph node involvement: final analysis with 7 years of follow-up Ann. Onc., May 1, 2002; 13(5): 689 - 698. [Abstract] [Full Text] [PDF]

				Y. Nieto, S. Nawaz, R. B. Jones, E. J. Shpall, P. J. Cagnoni, P. A. McSweeney, A. Baron, C. Razook, S. Matthes, and S. I. Bearman Prognostic Model for Relapse After High-Dose Chemotherapy With Autologous Stem-Cell Transplantation for Stage IV Oligometastatic Breast Cancer J. Clin. Oncol., February 1, 2002; 20(3): 707 - 718. [Abstract] [Full Text] [PDF]

				Y. S. Kim, S. N. Konoplev, F. Montemurro, E. Hoy, T. L. Smith, G. Rondon, R. E. Champlin, A. A. Sahin, and N. T. Ueno HER-2/neu Overexpression As a Poor Prognostic Factor for Patients with Metastatic Breast Cancer undergoing High-dose Chemotherapy with Autologous Stem Cell Transplantation Clin. Cancer Res., December 1, 2001; 7(12): 4008 - 4012. [Abstract] [Full Text] [PDF]