Long-term heart function after adjuvant epirubicin chemotherapy for breast cancer.
BACKGROUND
Newer studies raise concern that adjuvant anthracycline treatment for breast cancer (BC) causes long-term heart damage. We aimed to examine whether heart failure or impairment could be demonstrated several years after low-dose epirubicin-based adjuvant treatment.


METHODS
The study-population was a historical cohort comprising 980 women who were randomized to receive one of two adjuvant regimens for treatment for BC: 7-9 cycles of cyclophosphamide-epirubicin-5-fluorouracil [CEF (600 + 60 + 600 mg/m(2))] or cyclophosphamide-methotrexate-5- fluorouracil [CMF (600 + 40 + 600 mg/m(2))]. We collected information in national registries of death and diagnoses and a sample of 77 survivors was examined with tissue-Doppler imaging (TDI), echocardiography, radionuclide ventriculography and N-terminal-pro-B-type-natriuretic peptide (NT-proBNP), an established marker for heart failure.


CONCLUSIONS
Median follow-up was 12 years (39 days-20 years). Fifty-one percent had died. Incidence of CHF was 2.6/1000/year and equal in the treatment groups. In the sample, individuals who had received CEF showed no cardiac impairment when compared to individuals who received CMF. NT-proBNP-levels were within normal limits but higher in the CEF-group than in the CMF-group (confidence limits 105-226%, p = 0.03). Results of our study seem reassuring regarding the long-term risk of cardiotoxicity following low-dose adjuvant epirubicin treatment. However, larger, longitudinal studies are needed to establish the clinical implications.
Department of Cardiology, Herlev Hospital, Copenhagen, Denmark. jomiap02@heh.regionh.dk
Jon M
JM
Appel
Bo
B
Zerahn
Susanne
S
Møller
Heidi M
HM
Christensen
Peter
P
Søgaard
Bent
B
Ejlertsen
Niels
N
Fogh-Andersen
Benny V
BV
Jensen
Dorte L
DL
Nielsen
D000328:Adult; D000368:Aged; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000008:administration & dosage* / Q000009:adverse effects*; D015415:Biomarkers / Q000097:blood; D001943:Breast Neoplasms / Q000188:drug therapy* / Q000601:surgery; D017024:Chemotherapy, Adjuvant / Q000009:adverse effects; D015331:Cohort Studies; D003520:Cyclophosphamide / Q000008:administration & dosage / Q000009:adverse effects; D003718:Denmark; D004334:Drug Administration Schedule; D004452:Echocardiography / Q000379:methods; D015251:Epirubicin / Q000008:administration & dosage / Q000009:adverse effects; D005260:Female; D005472:Fluorouracil / Q000008:administration & dosage / Q000009:adverse effects; D005500:Follow-Up Studies; D006321:Heart / Q000000981:diagnostic imaging / Q000187:drug effects*; D006333:Heart Failure / Q000097:blood / Q000139:chemically induced* / Q000000981:diagnostic imaging / Q000503:physiopathology; D006801:Humans; D008727:Methotrexate / Q000008:administration & dosage / Q000009:adverse effects; D008875:Middle Aged; D020097:Natriuretic Peptide, Brain / Q000097:blood; D010446:Peptide Fragments / Q000097:blood; D015635:Radionuclide Ventriculography; D012042:Registries; D013318:Stroke Volume / Q000187:drug effects; D013997:Time Factors
D015415:Biomarkers; D010446:Peptide Fragments; C109794:pro-brain natriuretic peptide (1-76); D020097:Natriuretic Peptide, Brain; D015251:Epirubicin; D003520:Cyclophosphamide; D005472:Fluorouracil; D008727:Methotrexate