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Cardiac assessment of early breast cancer patients 18 years after treatment with cyclophosphamide-, methotrexate-, fluorouracil- or epirubicin-based chemotherapy

par de Azambuja, Evandro ;Ameye, Lieveke;Diaz, Marie;Vandenbossche, Sandrine ;Aftimos, Philippe ;Hernández, Sara Bejarano;Chao, Shih-Li ;Delhaye, François ;Focan, Christian;Cornez, Nathalie ;Vindevoghel, Anita;Beauduin, Marc;Lemort, Marc ;Paesmans, Marianne ;Suter, Thomas;Piccart-Gebhart, Martine
Référence European journal of cancer, 51, 17, page (2517-2524)
Publication Publié, 2015-11

Article révisé par les pairs

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Résumé :

Background Epirubicin-based chemotherapy improves the outcome of early breast cancer (BC) patients. However, cardiotoxicity remains an important side effect. Methods We re-consented node-positive BC patients enrolled in a phase III trial between 1988 and 1996 which compared six cycles of oral cyclophosphamide, methotrexate, fluorouracil (CMF) versus two epirubicin-cyclophosphamide regimens differing by the anthracycline cumulative dose [standard-dose epirubicin and cyclophosphamide (SDE) (8 × 60 mg/m2) and higher-dose epirubicin and cyclophosphamide (HDE) (8 × 100 mg/m2)]. Eligible patients were those who were alive and free of disease and had no contra-indications to the proposed tests (cardiac evaluation). Cardiotoxicity was defined as asymptomatic systolic dysfunction (left ventricular ejection fraction (LVEF) < 50%, New York Heart Association (NYHA) Class I) or symptomatic heart failure (NYHA Class II-IV). Differences in cardiotoxicity between CMF and SDE/HDE were assessed using chi-square and Fisher Exact tests for binary variables and t-test and Wilcoxon test for continuous variables. Results Among the 777 patients, 20 cases of CHF were reported (CMF = 1, SDE = 5, HDE = 14; p < 0.001). Between September 2010 and June 2013, 82 patients (30%) out of 269 eligible patients accepted to participate in this substudy. Median follow-up was 18 years (range 15-24). Epirubicin-treated patients had significantly higher heart rate, more abnormal echocardiograms and LVEF by magnetic resonance imaging (MRI) compared to CMF-treated ones. A trend towards higher BNP was also observed in the SDE/HDE group (P = 0.08). No differences were observed in LVEF assessed by echocardiogram or troponin T levels. Conclusions Participation rate in this substudy was lower than expected highlighting the complexity of re-calling patients several years after the initial BC diagnosis. After 18 years, epirubicin-treated patients had a lower LVEF by MRI, more abnormal echocardiograms, higher heart rates compared to patients treated with CMF. However, no major delayed cardiotoxicity was observed.