PMID- 26321502
OWN - NLM
STAT- MEDLINE
DCOM- 20160401
LR  - 20191210
IS  - 1879-0852 (Electronic)
IS  - 0959-8049 (Linking)
VI  - 51
IP  - 17
DP  - 2015 Nov
TI  - Cardiac assessment of early breast cancer patients 18 years after treatment with 
      cyclophosphamide-, methotrexate-, fluorouracil- or epirubicin-based chemotherapy.
PG  - 2517-24
LID - S0959-8049(15)00801-1 [pii]
LID - 10.1016/j.ejca.2015.08.011 [doi]
AB  - 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 x 60 mg/m(2)) and higher-dose epirubicin and 
      cyclophosphamide (HDE) (8 x 100 mg/m(2))]. 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.
CI  - Copyright (c) 2015 Elsevier Ltd. All rights reserved.
FAU - de Azambuja, Evandro
AU  - de Azambuja E
AD  - Department of Medicine, Institut Jules Bordet, Universite Libre de Bruxelles, 
      Brussels, Belgium. Electronic address: evandro.azambuja@bordet.be.
FAU - Ameye, Lieveke
AU  - Ameye L
AD  - Data Centre, Institut Jules Bordet, Universite Libre de Bruxelles, Brussels, 
      Belgium.
FAU - Diaz, Marie
AU  - Diaz M
AD  - Department of Oncology, Hopital Ambroise Pare, Mons, Belgium.
FAU - Vandenbossche, Sandrine
AU  - Vandenbossche S
AD  - Neuropsychologue CHIREC, Brussels, Belgium.
FAU - Aftimos, Philippe
AU  - Aftimos P
AD  - Department of Medicine, Institut Jules Bordet, Universite Libre de Bruxelles, 
      Brussels, Belgium.
FAU - Bejarano Hernandez, Sara
AU  - Bejarano Hernandez S
AD  - Department of Medicine, Institut Jules Bordet, Universite Libre de Bruxelles, 
      Brussels, Belgium.
FAU - Shih-Li, Chao
AU  - Shih-Li C
AD  - Department of Radiology, Institut Jules Bordet, Universite Libre de Bruxelles, 
      Brussels, Belgium.
FAU - Delhaye, Francois
AU  - Delhaye F
AD  - Cardiology Department, Institut Jules Bordet, Universite Libre de Bruxelles, 
      Brussels, Belgium.
FAU - Focan, Christian
AU  - Focan C
AD  - Department of Oncology, CHC-Clinique Saint-Joseph, Liege, Belgium.
FAU - Cornez, Nathalie
AU  - Cornez N
AD  - Department of Oncology, CHU Tivoli - GOHH, La Louviere, Belgium.
FAU - Vindevoghel, Anita
AU  - Vindevoghel A
AD  - Clinique Ste-Elisabeth, Namur, Belgium.
FAU - Beauduin, Marc
AU  - Beauduin M
AD  - Department of Oncology, Hopital de Jolimont, Haine St Paul, Belgium.
FAU - Lemort, Marc
AU  - Lemort M
AD  - Department of Radiology, Institut Jules Bordet, Universite Libre de Bruxelles, 
      Brussels, Belgium.
FAU - Paesmans, Marianne
AU  - Paesmans M
AD  - Data Centre, Institut Jules Bordet, Universite Libre de Bruxelles, Brussels, 
      Belgium.
FAU - Suter, Thomas
AU  - Suter T
AD  - Swiss Cardiovascular Center, Inselspital, Bern University Hospital, Bern, 
      Switzerland.
FAU - Piccart-Gebhart, Martine
AU  - Piccart-Gebhart M
AD  - Department of Medicine, Institut Jules Bordet, Universite Libre de Bruxelles, 
      Brussels, Belgium.
LA  - eng
SI  - ClinicalTrials.gov/NCT01554943
PT  - Clinical Trial, Phase III
PT  - Journal Article
PT  - Multicenter Study
PT  - Randomized Controlled Trial
PT  - Research Support, Non-U.S. Gov't
DEP - 20150827
PL  - England
TA  - Eur J Cancer
JT  - European journal of cancer (Oxford, England : 1990)
JID - 9005373
RN  - 3Z8479ZZ5X (Epirubicin)
RN  - 8N3DW7272P (Cyclophosphamide)
RN  - U3P01618RT (Fluorouracil)
RN  - YL5FZ2Y5U1 (Methotrexate)
SB  - IM
MH  - Adult
MH  - Antineoplastic Combined Chemotherapy Protocols/adverse effects/*therapeutic use
MH  - Breast Neoplasms/*drug therapy/mortality
MH  - Chemotherapy, Adjuvant/methods
MH  - Cyclophosphamide/administration & dosage/adverse effects
MH  - Disease-Free Survival
MH  - Dose-Response Relationship, Drug
MH  - Echocardiography
MH  - Epirubicin/administration & dosage/adverse effects
MH  - Female
MH  - Fluorouracil/administration & dosage/adverse effects
MH  - Follow-Up Studies
MH  - Heart Failure/chemically induced/diagnostic imaging/physiopathology
MH  - Humans
MH  - Methotrexate/administration & dosage/adverse effects
MH  - Middle Aged
MH  - Neoplasm Recurrence, Local
MH  - Outcome Assessment, Health Care/methods/statistics & numerical data
MH  - Prognosis
MH  - Proportional Hazards Models
MH  - Survival Rate
MH  - Ventricular Dysfunction, Left/chemically induced/diagnostic 
      imaging/physiopathology
OTO - NOTNLM
OT  - Adjuvant therapy
OT  - Late cardiac toxicity
OT  - Node-positive breast cancer
EDAT- 2015/09/01 06:00
MHDA- 2016/04/02 06:00
CRDT- 2015/09/01 06:00
PHST- 2015/03/26 00:00 [received]
PHST- 2015/08/06 00:00 [revised]
PHST- 2015/08/11 00:00 [accepted]
PHST- 2015/09/01 06:00 [entrez]
PHST- 2015/09/01 06:00 [pubmed]
PHST- 2016/04/02 06:00 [medline]
AID - S0959-8049(15)00801-1 [pii]
AID - 10.1016/j.ejca.2015.08.011 [doi]
PST - ppublish
SO  - Eur J Cancer. 2015 Nov;51(17):2517-24. doi: 10.1016/j.ejca.2015.08.011. Epub 2015 
      Aug 27.