Elevation of Serum NT-Pro BNP Correlates with Asymptomatic Cardiac Dysfunction Induced by Doxorubicin.

Abstract

Abstract Background: Cardiac dysfunction is one of the major limitations of anthracycline treatment in cancer patients. Current reliable investigation to detect early cardiac damage from anthracycline is not available. There are several serum cardiac markers useful in other types of cardiomyopathy including NT-pro BNP, Troponin-T, and CK-MB. We chose to investigate potential application of these serum biomarkers in the cancer patients receiving anthracycline.Patients and methods: We prospectively collected data from a cohort of 52 female breast cancer patients who receiving doxorubicin and cyclophosphamide (AC) regimen every 3 weeks for 4 cycles for preoperative or postoperative adjuvant treatment. Cardiac function evaluations by echocardiography were done at baseline and post 4th cycle chemotherapy. Patients' blood samplings were serially measured for cardiac biomarkers at baseline, after 1st cycle, and after 4th cycle chemotherapy.Results: All patients were in good performance status with ECOG scale 0-1.The mean cumulative dose of doxorubicin in this study was 236.69 mg/m2. There was no symptomatic heart failure detected during study period. However, there were significant asymptomatic reductions of left ventricular ejection fraction (LVEF) from 70.73 ± 5.97% at baseline to 66.96 ± 5.48% (p<0.001). The severities of LVEF declination were 17.4% in grade1 and 3.8% in grade 2 by clinical toxicity criteria of NCI version 2. We found significant elevation of serum NT-proBNP (p = 0.044) following the first dose of chemotherapy when compared the measurements in patients who had reduction of LVEF to those with normal LVEF. Measurement of serum Troponin-T and CK-MB showed no significant correlation with changes in LVEF. Generalized-estimating-equations correlation analysis demonstrated that the reduction of fractional shortening (FS) was significantly associated with the elevation NT-pro BNP (r = -0.016, p = 0.014). At cutoff level 45 pg/mL, serum NT-proBNP had 100% sensitivity and 66.67% specificity for the detection of cardiotoxicity in patients under 50 year-old.Conclusion: Asymptomatic reductions in cardiac function are common in patients treated with doxorubicin. NT-pro BNP may serve as a potential convenient serum biomarker for early detection of cardiotoxicity induced by anthracycline. Citation Information: Cancer Res 2009;69(24 Suppl):Abstract nr 4003.