This Article Full Text Full Text (PDF) Erratum (v21,p4469) 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 Weiss, R. B. Articles by Norton, L. Search for Related Content PubMed PubMed Citation Articles by Weiss, R. B. Articles by Norton, L. Social Bookmarking                            What's this?

Natural History of More Than 20 Years of Node-Positive Primary Breast Carcinoma Treated With Cyclophosphamide, Methotrexate, and Fluorouracil–Based Adjuvant Chemotherapy: A Study by the Cancer and Leukemia Group B

Raymond B. Weiss, Susan H. Woolf, Erin Demakos, James F. Holland, Donald A. Berry, Geoffrey Falkson, Constance T. Cirrincione, Alice Robbins, Sandra Bothun, I. Craig Henderson, Larry Norton

From the Walter Reed Army Medical Center, and Georgetown University Medical Center, Washington, DC; Cancer and Leukemia Group B Statistical and Data Management Centers, Duke University, Durham, NC; Mt Sinai School of Medicine, and Memorial Sloan-Kettering Cancer Center, New York, NY; West Virginia University Medical Center, Morgantown, WV; University of California at San Francisco, San Francisco, CA; and University of Pretoria, Pretoria, South Africa.

Address reprint requests to Raymond B. Weiss, MD, 15304 Narcissus Way, Rockville, MD 20853-1744; email: RayWeissMD{at}aol.com.

Purpose: Breast cancer heterogeneity dictates lengthy follow-up to assess outcomes. Efficacy differences for three regimens that are based on adjuvant cyclophosphamide, methotrexate, and fluorouracil (CMF) are presented in this article, but cancer recurrence sites, time of relapse, subsequent primary cancers, and causes of death in the natural history of node-positive breast cancer are emphasized.

Patients and Methods: Beginning in 1975, 905 patients with node-positive cancer were randomly assigned to receive CMF or two regimens of CMF plus other agents. Median follow-up is 22.6 years. The natural-history analysis was performed on a subset of 814 patients.

Results: Eighty percent of the 599 women known to have died, died of metastatic breast cancer. Only 8.5% of the deceased women died of a cause other than breast cancer, a second or third cancer, or adjuvant chemotherapy toxicity. One hundred five women (12.8%) developed other primary cancers, with 49 (46.6%) occurring in the contralateral breast. Therapeutic efficacy differences of the CMF regimens reported earlier have been maintained more than 20 years later. For certain subsets, the five-drug regimen had advantages over CMF. Bone was the most common recurrence site. The longest interval to relapse has been 23.5 years, and 18% of those who relapsed did so more than 10 years later.

Conclusion: Despite adjuvant chemotherapy, a large majority (80%) of women with node-positive breast cancer die of the disease, and many recurrences develop more than 10 years later. CMF plus vincristine and prednisone provides a benefit compared with CMF, but the magnitude varies with the number of involved nodes. Outcome trends in earlier analyses of this study were maintained even years later.

Supported in part by the following grant nos. CA 26806, CA 31946, CA 33601, CA 04457, CA 28562, CA 60138, CA 77597, and CA 77651 from the National Cancer Institute, Bethesda, MD, to the Cancer and Leukemia Group B.

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

This article has been cited by other articles:

				S. E. Wolowacz, D. A. Cameron, H. C. Tate, and A. Bagust Docetaxel in Combination With Doxorubicin and Cyclophosphamide As Adjuvant Treatment for Early Node-Positive Breast Cancer: A Cost-Effectiveness and Cost-Utility Analysis J. Clin. Oncol., February 20, 2008; 26(6): 925 - 933. [Abstract] [Full Text] [PDF]

				M.-C. Le Deley, F. Suzan, B. Cutuli, S. Delaloge, A. Shamsaldin, C. Linassier, S. Clisant, F. de Vathaire, P. Fenaux, and C. Hill Anthracyclines, Mitoxantrone, Radiotherapy, and Granulocyte Colony-Stimulating Factor: Risk Factors for Leukemia and Myelodysplastic Syndrome After Breast Cancer J. Clin. Oncol., January 20, 2007; 25(3): 292 - 300. [Abstract] [Full Text] [PDF]

				C. A. Hudis and E. P. Winer Cancer and leukemia group B breast committee: decades of progress and plans for the future. Clin. Cancer Res., June 1, 2006; 12(11): 3576s - 3580s. [Abstract] [Full Text] [PDF]

				E. Espinosa, J.A. F. Vara, A. Redondo, J.J. Sanchez, D. Hardisson, P. Zamora, F. G. Pastrana, P. Cejas, B. Martinez, A. Suarez, et al. Breast Cancer Prognosis Determined by Gene Expression Profiling: A Quantitative Reverse Transcriptase Polymerase Chain Reaction Study J. Clin. Oncol., October 10, 2005; 23(29): 7278 - 7285. [Abstract] [Full Text] [PDF]

				H. B. Muss, S. Woolf, D. Berry, C. Cirrincione, R. B. Weiss, D. Budman, W. C. Wood, I. C. Henderson, C. Hudis, E. Winer, et al. Adjuvant Chemotherapy in Older and Younger Women With Lymph Node-Positive Breast Cancer JAMA, March 2, 2005; 293(9): 1073 - 1081. [Abstract] [Full Text] [PDF]

				J. A. Low, A. W. Berman, S. M. Steinberg, D. N. Danforth, M. E. Lippman, and S. M. Swain Long-Term Follow-Up for Locally Advanced and Inflammatory Breast Cancer Patients Treated With Multimodality Therapy J. Clin. Oncol., October 15, 2004; 22(20): 4067 - 4074. [Abstract] [Full Text] [PDF]