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 Journal Article


Authors: Weiss, R. B.; Woolf, S. H.; Demakos, E.; Holland, J. F.; Berry, D. A.; Falkson, G.; Cirrincione, C. T.; Robbins, A.; Bothun, S.; Henderson, I. C.; Norton, L.
Article Title: 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
Abstract: 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. © 2003 by American Society of Clinical Oncology.
Keywords: adult; controlled study; aged; middle aged; leukemia; major clinical study; prednisone; clinical trial; disease course; anamnesis; cancer localization; cancer recurrence; fluorouracil; drug efficacy; bone metastasis; cancer adjuvant therapy; chemotherapy, adjuvant; methotrexate; follow up; follow-up studies; lymph node metastasis; antineoplastic agent; lymphatic metastasis; lymph node excision; lymphadenectomy; metastasis; controlled clinical trial; neoplasm recurrence, local; mastectomy; randomized controlled trial; antineoplastic combined chemotherapy protocols; cyclophosphamide; vincristine; pathology; breast neoplasms; cause of death; drug fatality; disease progression; multicenter study; tumor recurrence; adjuvant chemotherapy; breast tumor; lymph node; breast carcinoma; neoplasm metastasis; medical society; cancer relapse; axilla; cmf regimen; humans; human; female; priority journal; article
Journal Title: Journal of Clinical Oncology
Volume: 21
Issue: 9
ISSN: 0732-183X
Publisher: American Society of Clinical Oncology  
Date Published: 2003-05-01
Start Page: 1825
End Page: 1835
Language: English
DOI: 10.1200/jco.2003.09.006
PUBMED: 12721260
PROVIDER: scopus
DOI/URL:
Notes: Export Date: 12 September 2014 -- Source: Scopus
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  1. Larry Norton
    758 Norton