title: Long-term cardiac sequelae in operable breast cancer patients given adjuvant chemotherapy with or without doxorubicin and breast irradiation.
abstract: OBJECTIVE
  To investigate long-term cardiac sequelae associated with anthracycline use in adjuvant chemotherapy of patients with early breast cancer.
  
  
  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.
  
  
  CONCLUSIONS
  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.affiliation: Istituto Nazionale Tumori, Milan, Italy.
authors.forename: M
authors.initials: M
authors.lastname: Zambetti
authors.forename: A
authors.initials: A
authors.lastname: Moliterni
authors.forename: C
authors.initials: C
authors.lastname: Materazzo
authors.forename: M
authors.initials: M
authors.lastname: Stefanelli
authors.forename: S
authors.initials: S
authors.lastname: Cipriani
authors.forename: P
authors.initials: P
authors.lastname: Valagussa
authors.forename: G
authors.initials: G
authors.lastname: Bonadonna
authors.forename: L
authors.initials: L
authors.lastname: Gianni
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000903:Antibiotics, Antineoplastic / Q000009:adverse effects*; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000627:therapeutic use; D001943:Breast Neoplasms / Q000188:drug therapy* / Q000532:radiotherapy; D017024:Chemotherapy, Adjuvant / Q000009:adverse effects; D003131:Combined Modality Therapy; D004317:Doxorubicin / Q000009:adverse effects*; D005260:Female; D005500:Follow-Up Studies; D006331:Heart Diseases / Q000139:chemically induced* / Q000453:epidemiology; D006801:Humans; D015994:Incidence; D007558:Italy / Q000453:epidemiology; D008875:Middle Aged
chemical_list: D000903:Antibiotics, Antineoplastic; D004317:Doxorubicin