Prospective evaluation of early cardiac damage induced by epirubicin-containing adjuvant chemotherapy and locoregional radiotherapy in breast cancer patients.
OBJECTIVE
To evaluate prospectively the cardiotoxic effects of epirubicin-containing adjuvant chemotherapy in breast cancer patients.


METHODS
Patients (median age, 46 years; range, 28 to 55 years) were treated with five cycles of fluorouracil, epirubicin (90 mg/m2), and cyclophosphamide (FEC) (group I, n = 21) or with four cycles of FEC followed by high-dose chemotherapy consisting of cyclophosphamide, thiotepa, and carboplatin (group II, n = 19). Locoregional radiotherapy was applied subsequently. Cardiac evaluation was performed before chemotherapy (T0), 1 month after chemotherapy, 1 month after radiotherapy (T2), and 1 year after start of chemotherapy (T3). Left ventricular ejection fraction (LVEF) was determined by radionuclide ventriculography and diastolic function by echocardiography. Autonomic function was assessed by 24-hour ECG registration for heart rate variability (HRV) analysis. Time-corrected QT (QTc) was assessed and N-terminal atrial natriuretic peptide (NT-ANP) and brain natriuretic peptide (BNP) were measured as biochemical markers of cardiac dysfunction.


RESULTS
No patient developed overt congestive heart failure (CHF) and the mean LVEF declined from 0.61 at T0 to 0.54 at T3 (P =.001), resulting in an LVEF below 0.50 (range, 0.42 to 0.49) in 17% of the patients, whereas 28% had a decline of more than 0.10. Plasma NT-ANP levels increased gradually from 237 pmol/L at T0 to 347 pmol/L at T3 (P <.01), whereas plasma BNP levels increased from 2.9 pmol/L to 5.1 pmol/L (P =.04). Mean QTc increased from 406 msec at T0 to 423 msec at T3 (P <.01). No persistent alterations were found in diastolic function and HRV.


CONCLUSIONS
Relatively low doses of epirubicin in adjuvant chemotherapy for breast cancer results in mild subclinical myocardial damage demonstrated by a decline in LVEF, an increase in natriuretic peptide levels, and an increase in QTc, which may indicate a long-term risk of CHF.
Meinardi
M T
MT
Department of Medical Oncology, University Hospital, Groningen, The Netherlands.
van Veldhuisen
D J
DJ
Gietema
J A
JA
Dolsma
W V
WV
Boomsma
F
F
van den Berg
M P
MP
Volkers
C
C
Haaksma
J
J
de Vries
E G
EG
Sleijfer
D T
DT
van der Graaf
W T
WT
D000328:Adult; D000903:Antibiotics, Antineoplastic / Q000009:adverse effects* / Q000627:therapeutic use; D009320:Atrial Natriuretic Factor / Q000097:blood; D001943:Breast Neoplasms / Q000188:drug therapy* / Q000532:radiotherapy*; D009202:Cardiomyopathies / Q000139:chemically induced* / Q000000981:diagnostic imaging; D017024:Chemotherapy, Adjuvant / Q000009:adverse effects*; D004562:Electrocardiography; D015251:Epirubicin / Q000009:adverse effects* / Q000627:therapeutic use; D005260:Female; D006801:Humans; D008875:Middle Aged; D011446:Prospective Studies; D014463:Ultrasonography; D015646:Ventriculography, First-Pass
D000903:Antibiotics, Antineoplastic; D015251:Epirubicin; D009320:Atrial Natriuretic Factor