By using N-terminal proatrial natriuretic peptide (proANP) in serum as a marker of cardiac function, we compared the cardiac side effects of two intensive adjuvant treatment regimens for breast cancer. Patients received either 9 cycles of FEC (5-fluorouracil, epirubicin and cyclophosphamide) where the doses of epirubicin and cyclophosphamide were escalated according to the leucocyte nadir (n = 49, FEC-group) or three cycles of FEC followed by high-dose chemotherapy with alkylating agents (n = 56, CTCb-group) given with the support of peripheral blood stem cells support. Both groups received adjuvant radiotherapy. Serial measurements of proANP were performed up to three years after treatment. Mean proANP values in the FEC-group was on average 19% higher than in the CTCb-group (p = 0.002). The proANP levels showed a significant association with the cumulative dose of epirubicin (p < 0.001) but not with cyclophosphamide (p = 0.151) and 5-FU (p = 0.160). The pharmacokinetics of epirubicin was studied at the first and third chemotherapy course. The proANP levels after treatment were significantly related to the AUC (p = 0.034) and Cmax(p = 0.037) of epirubicin. Left-sided chest irradiation was associated with on average 12% higher proANP values than right-sided (p = 0.031). We conclude that dose-escalated FEC causes a stronger increase in proANP than 3 FEC followed by high-dose CTCb-treatment. Increase of proANP levels might represent an early sign of cardiotoxicity secondary to chemotherapy and radiation treatment. Long-time follow-up is necessary to determine the clinical significance of these findings.