Prospective evaluation of cardiac safety in breast cancer patients after adjuvant treatment with epirubicin, cyclophosphamide, doxetaxel and with or without trastuzumab: A single center experience

Anticancer drugs can cause cardiotoxicity. Chemotherapy with antracyclines is associated with electrocardiographic alterations including prolongation of the corrected QT (QTc) interval with the risk of life threatening arrhythmias. Among the new targeted therapies QTc aberrations were reported upon treatment with anti HER2/neu agents. The combination of the antracycline epirubicin and monoclonal antibody trastuzumab against HER2/neu positive breast cancers might potentiate this cardiotoxic effect.

In this observational study we assessed the cardiac safety in 19 adjuvant treated breast cancer patients. All 9 HER2/neu positive breast cancer patients were assigned to receive 4 cycles of E90C600 i.v. q3w followed by 4 cycles of doxetaxel100 q3w combined with trastuzumab q3w up to 18 cycles. To investigate the effect of trastuzumab we included 10 HER2/neu positive breast cancer patients receiving the same treatment without trastuzumab. Cardiac toxicity was assessed with symptoms, transthoracic echocardiography, electrocardiography and biochemical markers (brain natriuretic peptide (NT-proBNP), creatine kinase (CK) and creatine kinase-MB) at baseline, after receiving EC, after first doxetaxel before and directly after the first trastuzumab treatment and after 4 cycles of trastuzumab.

There was a significant trend towards a QTc-prolongation after the EC treatment in all patients (baseline: 426 ± 41 ms vs. 4 cycles EC: 455 ± 34 ms; p = 0,0195), which is recovering over time. No effect of trastuzumab on the QTc-interval was observed directly after application or after four cycles. A significant increase of the NT-proBNP was noted after the EC treatment (74,00 ± 54,24 ng/l vs. 138,5 ± 108,3 ng/l p = 0,03). Other biochemical markers were within normal ranges. There was no statistically significant relationship between trastuzumab treatment and the levels of biochemical markers. No clinically relevant changes in LVEF after EC and trastuzumab were observed.

This study demonstrated that EC treatment might increase QTc-prolongation and NT-proBNP levels in women with early breast cancer indicating cardiac dysfunction. However, no additional clinically relevant effects on QTc and other electrocardiogram parameters were observed in patients treated with trastuzumab. Due to the small number of patients further conclusions are limited. In summary, cardiac monitoring should be offered to patients receiving specific anticancer drugs to reduce the risk of cardiac events.