Long-term cardiac sequelae in operable breast cancer patients given adjuvant chemotherapy with or without doxorubicin and breast irradiation.

Abstract

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/m(2)) 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.

• Authors: M Zambetti, A Moliterni, C Materazzo, M Stefanelli, S Cipriani, P Valagussa, G Bonadonna, L Gianni
• Journal: Journal of clinical oncology : official journal of the American Society of Clinical Oncology (J Clin Oncol) Vol. 19 Issue 1 Pg. 37-43 (Jan 01 2001) ISSN: 0732-183X [Print] United States
• PMID: 11134193 (Publication Type: Journal Article)

Chemical References

• Antibiotics, Antineoplastic
• Doxorubicin

Topics

• Adult
• Aged
• Aged, 80 and over
• Antibiotics, Antineoplastic (adverse effects)
• Antineoplastic Combined Chemotherapy Protocols (therapeutic use)
• Breast Neoplasms (drug therapy, radiotherapy)
• Chemotherapy, Adjuvant (adverse effects)
• Combined Modality Therapy
• Doxorubicin (adverse effects)
• Female
• Follow-Up Studies
• Heart Diseases (chemically induced, epidemiology)
• Humans
• Incidence
• Italy (epidemiology)
• Middle Aged