Role of renal function on the development of cardiotoxicity associated with trastuzumab-based adjuvant chemotherapy for early breast cancer

Abstract

Anthracyclines, taxanes and trastuzumab are used for therapy in early breast cancer (EBC) overexpressing Human Epidermal Growth Factor 2 (HER2+). These drugs, considered alone, do not present potential nephrotoxicity. However, renal dysfunction (RD) may increase the myocardial sensibility to the insult of these chemotherapies used in combination. The aim of the study is to assess the role of RD on the development of cardiotoxicity associated with trastuzumab-based adjuvant therapy (aTrastC) for EBC. Clinical and echocardiographic data of 499 women with ERB2+ EBC were analyzed. At 12-month evaluation, any symptoms of heart failure or decrease in left ventricular ejection fraction (LVEF) were recorded. Patients who had cardiotoxicity (n = 130, 26 %) were older (57 ± 11 vs. 55 ± 11 years; p = 0.03), had lower glomerular filtration rate (GFR) (76 ± 15 vs. 83 ± 19 ml/min/1.73 m(2); p = 0.003), higher LVEF (69 ± 6 vs. 63 ± 5 %; p < 0.001) and received more frequent doses of doxorubicin (18 vs. 9 %; p = 0.01) than those who did not. In patients with GFR 60-90 and <60 ml/min/1.73 m(2), the 1-year event rate of cardiotoxicity was 25 and 38 %, respectively. ROC analysis showed that the best cut-off point of GFR for predicting cardiotoxicity was 78 ml/min/1.73 m(2) (AUC = 0.66, [95 % CI 0.57-0.74]). Multiple logistic regression revealed that GRF <78 ml/min/1.73 m(2) was the strongest predictor of cardiotoxicity (OR 3.32 [CI = 1.30-8.65]), independent of doxorubicin treatment and left ventricular ejection fraction. A reduced renal function represents a condition of higher risk of developing cardiotoxicity at 12-month follow-up in patients with HER2 + EBC treated with aTrastC.