Serum NT-proBNP in the early detection of doxorubicin-induced cardiac dysfunction.
OBJECTIVE
Cardiac dysfunction is a major limitation of anthracycline treatment in cancer patients. There are several useful serum markers in other types of cardiomyopathy, including N-terminal pro-brain-natriuretic peptide (NT-proBNP), troponin-T and creatine kinase MB isoform. We investigated the potential application of these serum biomarkers in cancer patients receiving treatment with anthracycline.


METHODS
We collected data from 52 female breast cancer patients receiving doxorubicin and cyclophosphamide every 3 weeks for four cycles. Cardiac function evaluations by echocardiography were done at baseline and at the end of the fourth cycle of chemotherapy. Patients' blood samples were serially measured for cardiac biomarkers.


RESULTS
The mean cumulative dose of doxorubicin in this study was 237 mg/m(2) . No symptomatic heart failure was detected during the study period. However, there were significant asymptomatic reductions of left ventricular ejection fraction (LVEF) from mean ± SD 70.7 ± 6% at baseline to 67.0 ± 5% (P < 0.001). By clinical toxicity criteria the LVEF decline was grade I in 18% and grade II in 4%. After one dose of chemotherapy, a significant rise of serum NT-proBNP occurred in patients who subsequently developed an LVEF reduction compared with patients with normal LVEF (P = 0.04). A correlation analysis demonstrated that the reduction of fractional shortening was significantly associated with elevated NT-proBNP (r = -0.016, P = 0.014).


CONCLUSIONS
Asymptomatic reductions in cardiac function are common in breast cancer patients treated with doxorubicin. NT-proBNP may serve as a convenient serum biomarker for the early detection of cardiotoxicity induced by anthracycline.
Division of Medical Oncology, Department of Medicine, Faculty of Medicine, Chulalongkorn University and King Chulalongkorn Memorial Hospital, Bangkok, Thailand.
Annop
A
Kittiwarawut
Yongkasem
Y
Vorasettakarnkij
Suebpong
S
Tanasanvimon
Sopark
S
Manasnayakorn
Virote
V
Sriuranpong
D000328:Adult; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000009:adverse effects*; D015415:Biomarkers / Q000097:blood*; D001943:Breast Neoplasms / Q000175:diagnosis / Q000453:epidemiology / Q000401:mortality*; D003520:Cyclophosphamide / Q000008:administration & dosage; D004317:Doxorubicin / Q000008:administration & dosage; D042241:Early Diagnosis; D004452:Echocardiography; D005260:Female; D005500:Follow-Up Studies; D006331:Heart Diseases / Q000139:chemically induced / Q000175:diagnosis*; D006801:Humans; D008875:Middle Aged; D020097:Natriuretic Peptide, Brain / Q000097:blood*; D009367:Neoplasm Staging; D010446:Peptide Fragments / Q000097:blood*; D011379:Prognosis; D011446:Prospective Studies
D015415:Biomarkers; D010446:Peptide Fragments; C109794:pro-brain natriuretic peptide (1-76); D020097:Natriuretic Peptide, Brain; D004317:Doxorubicin; D003520:Cyclophosphamide