ProANP and NT-proBNP levels to prospectively assess cardiac function in breast cancer patients treated with cardiotoxic chemotherapy.
BACKGROUND
Cardiac function impairment is a known side effect of epirubicin-based chemotherapy. Activation of natriuretic peptides is demonstrated in patients with heart failure.


OBJECTIVE
To identify prospectively the cardiotoxic profile of epirubicin-based chemotherapy in breast cancer patients and to evaluate the sensitivity of proANP and NT-proBNP as early biochemical markers of cardiac dysfunction.


METHODS
Forty cancer patients divided in two nonrandomized groups received either epirubicin and paclitaxel (Group A, n=26) or mitoxantrone and docetaxel (Group B, n=14). Control groups, Group C (n=13) and Group D (n=20), consisted of female patients with heart failure and healthy women respectively. Natriuretic peptides and LVEF were determined in all patients.


RESULTS
A statistically significant difference was recorded regarding LVEF before and after treatment in Group A patients (p=0.0001). Three patients had a significant LVEF decline between 10% and 18% from baseline values, while three reached an LVEF value below 50%. All of them presented an increase in proANP and NT-proBNP values (mean increase 270.31+/-124 fmol/ml and 303.57+/-108 fmol/ml, respectively). A significant correlation between the increase in plasma proANP (r=0.8, p<0.0001), as well as NT-proBNP (r=0.7, p<0.0001) and the decrease in LVEF was observed. Regarding Group A, levels of proANP increased from 192.25 fmol/ml before treatment to 287.84 fmol/ml after treatment (p=0.0001), whereas NT-proBNP increased from 152.50 to 242 fmol/ml (p<0.0001) respectively. During follow up, two Group A patients developed congestive heart failure twelve and fourteen months after the completion of chemotherapy respectively. A significant LVEF decline was recorded in both patients during the episode. Regarding Group B, no statistically significant differences were demonstrated.


CONCLUSIONS
ProANP and NT-proBNP levels might be used as reliable and sensitive markers in the detection of early cardiac impairment caused by epirubicin-based chemotherapy.
Kouloubinis
Alexandros
A
Onassis Cardiac Surgery Center, 2nd Department of Cardiology, 356 Siggrou Avenue, 17674, Athens, Greece.
Kaklamanis
Loukas
L
Ziras
Nikolaos
N
Sofroniadou
Sofia
S
Makaritsis
Konstantinos
K
Adamopoulos
Stamatios
S
Revela
Ioanna
I
Athanasiou
Athanasios
A
Mavroudis
Dimitrios
D
Georgoulias
Vasillios
V
D000328:Adult; D000970:Antineoplastic Agents / Q000633:toxicity*; D009320:Atrial Natriuretic Factor / Q000097:blood*; D015415:Biomarkers / Q000097:blood; D001943:Breast Neoplasms / Q000097:blood* / Q000188:drug therapy; D002318:Cardiovascular Diseases / Q000097:blood* / Q000139:chemically induced; D005260:Female; D006801:Humans; D008875:Middle Aged; D020097:Natriuretic Peptide, Brain / Q000097:blood*; D010446:Peptide Fragments / Q000097:blood*; D011446:Prospective Studies; D011498:Protein Precursors / Q000097:blood*
D000970:Antineoplastic Agents; D015415:Biomarkers; D010446:Peptide Fragments; D011498:Protein Precursors; C109794:pro-brain natriuretic peptide (1-76); C055659:atrial natriuretic factor prohormone (1-98); D020097:Natriuretic Peptide, Brain; D009320:Atrial Natriuretic Factor