Key result
Adjuvant epirubicin-based CEF shows equal long-term CHF incidence compared to CMF.
Why the study?
Newer studies raise concern that adjuvant anthracycline treatment for breast cancer causes long-term heart damage, but evidence after low-dose epirubicin is limited.
Does low-dose adjuvant epirubicin chemotherapy increase the long-term risk of heart failure or cardiac impairment compared to a non-anthracycline regimen in women with breast cancer?
RCT (n=980)
randomized
Does low-dose adjuvant epirubicin chemotherapy increase the long-term risk of heart failure or cardiac impairment compared to a non-anthracycline regimen in women with breast cancer?
Low-dose adjuvant epirubicin treatment for breast cancer does not appear to significantly increase the long-term risk of clinical heart failure compared to non-anthracycline regimens, though mild subclinical NT-proBNP elevations may occur.
Reassuring for low-dose epirubicin cardiotoxicity in survivors; leaves open questions on subtle NT-proBNP elevation and broader applicability.
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. MATERIAL AND 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. RESULTS AND CONCLUSION: 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.
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Appel et al. (2012) conducted an RCT in breast cancer (n=980). cyclophosphamide-epirubicin-5-fluorouracil (CEF) vs. cyclophosphamide-methotrexate-5-fluorouracil (CMF) was evaluated on Incidence of congestive heart failure (CHF). Adjuvant epirubicin-based chemotherapy (CEF) resulted in an equal long-term incidence of congestive heart failure compared to CMF (2.6/1000/year in both groups) over a median 12-year follow-up.
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