Journal of Clinical Oncology, Vol 15, 2882-2893, Copyright © 1997 by American Society of Clinical Oncology

ARTICLES

High-dose chemotherapy and stem-cell rescue in the treatment of high- risk breast cancer: prognostic indicators of progression-free and overall survival

G Somlo, JH Doroshow, SJ Forman, T Odom-Maryon, J Lee, W Chow, V Hamasaki, L Leong, R Morgan Jr, K Margolin, J Raschko, S Shibata, M Tetef, Y Yen, J Simpson and A Molina
Department of Medical Oncology and Therapeutics Research, City of Hope National Medical Center, Duarte, CA 91010, USA. gsomlo@smtplink.coh.org

PURPOSE: To examine the predictive value of tumor- and treatment- specific prognostic indicators of relapse-free survival (RFS) and overall survival (OS) in patients with high-risk breast cancer (HRBC) treated with high-dose chemotherapy (HDCT) and stem-cell rescue. PATIENTS AND METHODS: Between June 1989 and September 1994, 114 patients with HRBC (stage II with > or = 10 axillary lymph nodes involved, stage IIIA, and stage IIIB inflammatory carcinoma) received adjuvant chemotherapy followed by HDCT with etoposide, cyclophosphamide, and either doxorubicin (CAVP) or cisplatin (CCVP). Variables analyzed included stage, tumor size, number of axillary nodes involved, grade and receptor status, and types of adjuvant chemotherapy and radiation therapy and HDCT. RESULTS: With a median follow-up time of 46 months (range, 23 to 93), Kaplan-Meier estimates of 3.5-year OS for stage II, IIIA, and IIIB HRBC are 82% (95% confidence interval [CI], 67% to 97%), 79% (95% CI, 67% to 91%), and 72% (95% CI, 53% to 91%); RFS estimates are 71% (95% CI, 56% to 85%), 57% (95% CI, 43% to 72%), and 50% (95% CI, 29% to 71%) irrespective of the HDCT regimen. In univariate analysis, the risk of relapse was lower for patients with progesterone receptor (PR)-positive tumors (risk ratio [RR], 0.43; 95% CI, 0.22 to 0.81; P = .01) and higher for patients with inflammatory carcinoma (RR, 2.20; 95% CI, 1.02 to 4.76; P = .05). OS was better for patients with PR (RR, 0.16; 95% CI, 0.05 to 0.55; P = .003) and estrogen receptor (ER)-positive tumors (RR, 0.42; 95% CI, 0.17 to 1.02; P = .05); OS was worse for patients with high-grade primary tumors (RR, 4.08; 95% CI, 1.21-13.7; P = .02). In multivariate analysis, PR positivity was associated with improved RFS (P = .01) and OS (P = .001). CONCLUSION: HDCT in selected patients with HRBC is safe and warrants further evaluation. Patients with receptor-negative, high- grade, or inflammatory tumors require improvement in their therapeutic options. Better assessment of the role of HDCT awaits completion of ongoing randomized trials.

This article has been cited by other articles:

				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]

				M. S. Tallman, R. Gray, N. J. Robert, C. F. LeMaistre, C. K. Osborne, W. P. Vaughan, W. J. Gradishar, T. M. Pisansky, J. Fetting, E. Paietta, et al. Conventional Adjuvant Chemotherapy with or without High-Dose Chemotherapy and Autologous Stem-Cell Transplantation in High-Risk Breast Cancer N. Engl. J. Med., July 3, 2003; 349(1): 17 - 26. [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]

				P. Fumoleau, F. Chauvin, M. Namer, R. Bugat, M. Tubiana-Hulin, J. P. Guastalla, T. Delozier, P. Kerbrat, Y. Devaux, J. Bonneterre, et al. Intensification of Adjuvant Chemotherapy: 5-Year Results of a Randomized Trial Comparing Conventional Doxorubicin and Cyclophosphamide With High-Dose Mitoxantrone and Cyclophosphamide With Filgrastim in Operable Breast Cancer With 10 or More Involved Axillary Nodes J. Clin. Oncol., February 1, 2001; 19(3): 612 - 620. [Abstract] [Full Text] [PDF]

				Y. Nieto, P. J. Cagnoni, S. Nawaz, E. J. Shpall, R. Yerushalmi, B. Cook, P. Russell, J. McDermit, J. Murphy, S. I. Bearman, et al. 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 J. Clin. Oncol., May 10, 2000; 18(10): 2070 - 2080. [Abstract] [Full Text] [PDF]

				G. N. Hortobagyi, A. U. Buzdar, R. L. Theriault, V. Valero, D. Frye, D. J. Booser, F. A. Holmes, S. Giralt, I. Khouri, B. Andersson, et al. Randomized Trial of High-Dose Chemotherapy and Blood Cell Autografts for High-Risk Primary Breast Carcinoma J Natl Cancer Inst, February 2, 2000; 92(3): 225 - 233. [Abstract] [Full Text] [PDF]

				R. B. Weiss The Randomized Trials of Dose-Intensive Therapy for Breast Cancer: What Do They Mean for Patient Care and Where Do We Go From Here? Oncologist, December 1, 1999; 4(6): 450 - 458. [Abstract] [Full Text]

				Y. Nieto, P. J. Cagnoni, E. J. Shpall, X. Xu, J. Murphy, J. Vredenburgh, N. J. Chao, S. I. Bearman, and R. B. Jones 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., November 1, 1999; 5(11): 3425 - 3431. [Abstract] [Full Text] [PDF]

				D. Adkins, R. Brown, K. Trinkaus, R. Maziarz, S. Luedke, C. Freytes, B. Needles, D. Wienski, P. Fracasso, T. Pluard, et al. Outcomes of High-Dose Chemotherapy and Autologous Stem-Cell Transplantation in Stage IIIB Inflammatory Breast Cancer J. Clin. Oncol., July 1, 1999; 17(7): 2006 - 2006. [Abstract] [Full Text] [PDF]

				G. Somlo, I. Sniecinski, A. ter Veer, J. Longmate, G. Knutson, S. Vuk-Pavlovic, R. Bhatia, W. Chow, L. Leong, R. Morgan, et al. Recombinant Human Thrombopoietin in Combination With Granulocyte Colony-Stimulating Factor Enhances Mobilization of Peripheral Blood Progenitor Cells, Increases Peripheral Blood Platelet Concentration, and Accelerates Hematopoietic Recovery Following High-Dose Chemotherapy Blood, May 1, 1999; 93(9): 2798 - 2806. [Abstract] [Full Text] [PDF]

				R. L. Basser, L. B. To, J. P. Collins, C. G. Begley, D. Keefe, J. Cebon, J. Bashford, S. Durrant, J. Szer, D. Kotasek, et al. Multicycle High-Dose Chemotherapy and Filgrastim-Mobilized Peripheral-Blood Progenitor Cells in Women With High-Risk Stage II or III Breast Cancer: Five-Year Follow-Up J. Clin. Oncol., January 1, 1999; 17(1): 82 - 82. [Abstract] [Full Text] [PDF]