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According to recent results presented at the 25th annual San Antonio Breast Cancer Symposium, the anthracycline-based regimen referred to as CEF demonstrates long-term superiority over the chemotherapy regimen CMF in patients with early-stage breast cancer, particularly those with 4 or more positive lymph nodes.

Breast cancer is the second leading cause of cancer deaths of women in the United States. Breast cancer that has not spread to distant sites in the body, but may have spread to local axillary (under the arm) lymph nodes, is considered early stage. Following surgical removal of their cancer, patients with early stage breast cancer are often offered chemotherapy as an adjuvant therapy in order to kill any remaining cancer cells that may have not been removed by surgery. Researchers continue to compare different chemotherapy combinations as adjuvant therapy for breast cancer, as new chemotherapy agents emerge into the clinical setting. However, the results of direct comparisons often take years to truly determine survival benefits.

The chemotherapy combination consisting of cyclophosphamide, methotrexate, and fluorouracil (CMF) was a commonly used adjuvant therapy for the treatment of breast cancer; however, only approximately 10% of oncology centers are currently utilizing CMF. Chemotherapy agents known as anthracyclines (Ellence® (epirubicin) and doxorubicin (Adriamycin®) have demonstrated significant anti-cancer activity in breast cancer and researchers initiated a clinical trial directly comparing CMF to CEF (cyclophosphamide, Ellence®, fluorouracil). This trial involved women who were not postmenopausal and had early-stage breast cancer with positive axillary nodes. Patients were randomly selected to receive CMF or CEF. At 106 month follow-up, cancer was 15% less likely to recur following treatment with CEF compared to CMF. In addition, overall estimated survival rates at 10 years following therapy were 62% for patients treated with CEF, compared to 58% for those treated with CMF.

When subgroups were analyzed, the 10-year cancer-free survival rate for women with just 1-3 positive axillary nodes was 60% for patients treated with CEF, compared to 56% for patients treated with CMF. However, the 10-year cancer-free survival rate for women with 4 or more positive axillary nodes was 40% for patients treated with CEF, compared to 28% for patients treated with CMF. Survival benefits of treatment with CEF occurred in both estrogen receptor-positive and estrogen receptor-negative breast cancer. Congestive heart failure (a condition that often leads to heart failure and may be caused by anthracyclines) occurred in 1.1% of patients treated with CEF, compared to 0.3% of patients treated with CMF. The rate of acute leukemias occurred in 1.1% of patients treated with CEF, compared to 0.4% of patients treated with CMF.

These researchers concluded that long-term outcomes of treatment with CEF appears superior to CMF as adjuvant therapy in early-stage, lymph node-positive breast cancer, particularly in patients with four or more positive nodes. Clinical trials are ongoing to compare different chemotherapy regimens, including the taxanes, as adjuvant therapy in breast cancer to determine optimal regimens. In addition, researchers are evaluating specific patient subgroups (i.e. patients who are HER2-positive or have a specific genetic profile) and their responses to different therapies. Patients with early-stage breast cancer may wish to speak with their physician about the risks and benefits of an anthracycline-based regimen or the participating in a clinical trial further evaluating adjuvant therapies. Two sources of information regarding ongoing clinical trials include the National Cancer Institute ( and also provides personalized clinical trial searches on behalf of patients.

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1.Levine M, Bramwell V, Pritchard K, et al. Randomized trial of intensive cyclophosphamide, epirubicin, and fluorouracil chemotherapy compared with cyclophosphamide, methotrexate, and fluorouracil in premenopausal women with node-positive breast cancer. National Cancer Institute of Canada Clinical Trials Group.

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2.Pritchard et al. Proceedings from the 25th annual San Antonio Breast Cancer Symposium. San Antonio, Texas. December 11-14, 2002.

3.Laino C, Carlson R. CEF anthracyline-based regimen continues demonstrated superiority to CMF. Oncology Times. Special Edition coverage of the 25th San Antonio Breast Cancer Symposium. February 2003.

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