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Factors Correlated With Progression-Free Survival After High-Dose Chemotherapy and Hematopoietic Stem Cell Transplantation for Metastatic Breast Cancer
Philip A. Rowlings, MBBS, MS;
Stephanie F. Williams, MD;
Karen H. Antman, MD;
Karen K. Fields, MD;
Joseph W. Fay, MD;
Elizabeth Reed, MD;
Corey J. Pelz, MS;
John P. Klein, PhD;
Kathleen A. Sobocinski, MS;
M. John Kennedy, MD;
Cesar O. Freytes, MD;
Philip L. McCarthy, Jr, MD;
Roger H. Herzig, MD;
Edward A. Stadtmauer, MD;
Hillard M. Lazarus, MD;
Andrew L. Pecora, MD;
Jacob D. Bitran, MD;
Steven N. Wolff, MD;
Robert Peter Gale, MD, PhD;
James O. Armitage, MD;
William P. Vaughan, MD;
Gary Spitzer, MD;
Mary M. Horowitz, MD, MS
JAMA. 1999;282:1335-1343.
Context Women with breast cancer are the most frequent recipients of high-dose chemotherapy followed by autologous hematopoietic stem cell transplantation (autotransplants) in North America. Despite widespread use, controversy exists about the benefits of and appropriate patients for this therapy.
Objective To determine factors associated with disease progression or death after autotransplantation in women with metastatic breast cancer.
Design Analysis of data collected retrospectively (January 1989 to 1992) and prospectively (1992 through January 1995) for the Autologous Blood and Marrow Transplant Registry.
Setting Sixty-three hospitals in North America, Brazil, and Russia.
Participants A total of 1188 consecutive women aged 18 to 70 years receiving autotransplants for metastatic or locally recurrent breast cancer, with a median follow-up of 29 months.
Main Outcome Measure Time to treatment failure (disease progression, disease recurrence, or death) after autotransplantation.
Results Factors associated with significantly (P<.05) increased risk of treatment failure in a Cox multivariate analysis included age older than 45 years (relative hazard, 1.17; 95% confidence interval [CI], 1.02-1.33), Karnofsky performance score less than 90% (1.27; 95% CI, 1.07-1.51), absence of hormone receptors (1.31; 95% CI, 1.15-1.51), prior use of adjuvant chemotherapy (1.31; 95% CI, 1.10-1.56), initial disease-free survival interval after adjuvant treatment of no more than 18 months (1.99; 95% CI, 1.62-2.43), metastases in the liver (1.47; 95% CI, 1.20-1.80) or central nervous system (1.56; 95% CI, 0.99-2.46 [approaches significance]) vs soft tissue, bone, or lung, 3 or more sites of metastatic disease (1.32; 95% CI, 1.13-1.54), and incomplete response vs complete response to standard-dose chemotherapy (1.65; 95% CI, 1.36-1.99). Receiving tamoxifen posttransplantation was associated with a reduced risk of treatment failure in women with hormone receptor–positive tumors (relative hazard, 0.60; 95% CI, 0.47-0.87). Women with no risk factors (n = 38) had a 3-year probability of progression-free survival of 43% (95% CI, 27%-61%) vs 4% (95% CI, 2%-8%) for women with more than 3 risk factors (n = 343).
Conclusion These data indicate that some women are unlikely to benefit from autotransplantation and should receive this treatment only after being provided with prognostic information and in the context of clinical trials attempting to improve outcome.
Author Affiliations: The Breast Cancer Working Committee of the Autologous Blood and Marrow Transplant Registry, Health Policy Institute, Medical College of Wisconsin, Milwaukee (Drs Rowlings, Klein, and Horowitz, and Mr Pelz and Ms Sobocinski); Section of Hematology/Oncology, University of Chicago Medical Center, Chicago, Ill (Dr Williams); Division of Medical Oncology, Columbia University, New York, NY (Dr Antman); Division of Bone Marrow Transplantation, H. Lee Moffitt Cancer Center, Tampa, Fla (Dr Fields); Sammons Cancer Center, Baylor University, Dallas, Tex (Dr Fay); Division of Oncology-Hematology, University of Nebraska Medical Center, Omaha (Drs Reed and Armitage); Oncology Center, Johns Hopkins Hospital, Baltimore, Md (Dr Kennedy); Adult Bone Marrow Transplant Program, University of Texas Health Science Center, San Antonio (Dr Freytes); Department of Medicine, Roswell Park Cancer Institute, Buffalo, NY (Dr McCarthy); James Graham Brown Cancer Center, University of Louisville, Louisville, Ky (Dr Herzig); Bone Marrow Transplant Program, University of Pennsylvania, Philadelphia (Dr Stadtmauer); Ireland Cancer Center, Case Western Reserve University, Cleveland, Ohio (Dr Lazarus); Hackensack University Medical Center, Hackensack, NJ (Dr Pecora); Division of Hematology/Oncology, Lutheran General Hospital Cancer Care Center, Park Ridge, Ill (Dr Bitran); Department of Medicine, Vanderbilt University, Nashville, Tenn (Dr Wolff); Division of Bone Marrow and Stem Cell Transplantation, Salick Health Care, Inc, Los Angeles, Calif (Dr Gale); Bone Marrow Transplant Program, University of Alabama, Birmingham (Dr Vaughan); and Bone Marrow Transplant Division, Georgetown University Hospital, Washington, DC (Dr Spitzer).
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