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Long-Term Cardiac Sequelae in Operable Breast Cancer Patients Given Adjuvant Chemotherapy With or Without Doxorubicin and Breast Irradiation

From the Istituto Nazionale Tumori, Milan, Italy.

Address reprint requests to Luca Gianni, MD, Istituto Nazionale Tumori, Via Venezian 1, 20133 Milano, Italy; email gianni@ istitutotumori.mi.it.

PURPOSE: To investigate long-term cardiac sequelae associated with anthracycline use in adjuvant chemotherapy of patients with early breast cancer.

PATIENTS AND METHODS: All 1,000 patients from three prospective trials of adjuvant chemotherapy containing doxorubicin (n = 637, median total dose of 294 mg/m²) or not containing the anthracycline (cyclophosphamide, methotrexate, and fluorouracil [CMF] regimen alone, n = 363) were analyzed for the relative incidence of congestive heart failure (CHF) and myocardial infarction (MI) during 14 years of follow-up. The 462 women continuously free of disease as of February 1996 were recalled, and 355 consented to undergo evaluation including 12-lead ECG and cardiac ultrasound with determination of left ventricular ejection fraction (LVEF) to assess the relative incidence of abnormalities in long-term survivors.

RESULTS: Among the 1,000 patients, there were six cases of CHF and three cases of MI. Cumulative cardiac mortality accounted for 0.4% (doxorubicin-treated = 0.6%; CMF-treated = 0). Eighteen (5%) of the 355 patients undergoing cardiac evaluation after median 11 years of follow-up presented systolic dysfunction as defined by pathologic (< 50%, n = 8) or borderline (50% to 55%, n = 10) LVEF. Systolic dysfunction was higher in doxorubicin-treated (15 of 192; 8%) than in CMF-treated patients (three of 150; 2%). Breast irradiation had a significant impact on the occurrence of early CHF (four of 116; 3%), but not on systolic dysfunctions.

CONCLUSION: At longer than 10 years of follow-up, the use of doxorubicin at a total dose commonly applied in regimens of adjuvant chemotherapy does not lead to cardiac clinical sequelae that counter-balance the benefit of treatment in patients with operable breast cancer who may be cured of their disease.

Presented in part at the Thirty-Fifth Annual Meeting of the American Society of Clinical Oncology, Atlanta, GA, May 15-18, 1999.

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