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Researchers from Italy have evaluated three breast cancer studies performed between 1973 and 1985 and concluded that adjuvant CMF (cyclophosphamide, methotrexate and fluorouracil) “benefits patients at risk of relapse of distant disease without evidence of detrimental effects in any of the examined groups.” The details of this report appeared in the February issue of the British Journal of Medicine.

Adjuvant chemotherapy is an established treatment modality for women with localized breast cancer at risk of relapse. However, there have been few if any long-term studies to determine if side effects of chemotherapy may cause long-term effects that might decrease survival. Such side effects could be myelodysplastic syndromes, cardiac damage, premature menopause or other unknown problems.

Researchers from Milan have evaluated the long-term outcomes of women enrolled in three trials. The first trial randomized patients with node-positive breast cancer to receive no further therapy of CMF after mastectomy. The second trial allocated pre-menopausal women to receive 6 or 12 cycles of CMF and the third trial was in women with node-negative, estrogen receptor-negative tumors. The median follow-up of these women was 28.5 years. The researchers concluded that relapse-free and overall survival was improved by CMF therapy, with 12 cycles of CMF not being superior to 6 cycles. Importantly, the trial in node-negative, estrogen-negative women also showed a survival benefit. Further analyses in estrogen-positive patients suggested that CMF works by a direct cytotoxic effect and not entirely by producing premature menopause. These authors concluded that the effects of adjuvant chemotherapy “are long lasting and may benefit patients with favorable and unfavorable prognostic indicators.”

This is a very important follow-up study, which will need to be repeated in more recently treated patients who have received more toxic regimens involving anthracyclines and taxanes. The long-term benefits of adjuvant chemotherapy should reassure women who have qualms about undergoing such treatment.

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Reference: Bonadonna G, Moliterni A, Zambetti M, et al. 30 years’ follow up of randomized studies of adjuvant CMF in operable breast cancer: cohort study. British Medical Journal. 2005;330:220-223.

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