IM - ORIGINAL Role of renal function on the development of cardiotoxicity associated with trastuzumab-based adjuvant chemotherapy for early breast cancer Giulia Russo • Giovanni Cioffi • Andrea Di Lenarda • Fausto Tuccia • Daniella Bovelli • Giuseppe Di Tano • Gianfranco Alunni • Stefania Gori • Pompilio Faggiano • Luigi Tarantini Received: 7 February 2012 / Accepted: 26 May 2012 / Published online: 20 June 2012 Ó SIMI 2012 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 myocar- dial 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 trast- uzumab-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 func- tion represents a condition of higher risk of developing car- diotoxicity at 12-month follow-up in patients with HER2 ? EBC treated with aTrastC. Keywords Trastuzumab Á Renal dysfunction Á Glomerular filtration rate Á Chemotoxicity Á Women Á Early breast cancer Introduction Chemotherapy with anthracyclines and taxanes followed by trastuzumab is largely used as adjuvant therapy in patients with early breast cancer (EBC) overexpressing Human Epidermal Growth Factor 2 (HER2?). However, such che- motherapeutic medications are potentially cardiotoxic, and may cause, in some cases, a decrease in left ventricular On behalf of ICARO (Italian CARdio-Oncologic) network. G. Russo (&) Á A. Di Lenarda Centro Cardiovascolare ASS1 Triestina, Via Slataper 9 34125 Trieste, Italy e-mail: giulia.russo@ass1.sanita.fvg.it G. Cioffi Department of Cardiology, Villa Bianca Hospital, Trento, Italy F. Tuccia Department of Oncology, ‘‘S. Martino’’ Hospital of Belluno, Belluno, Italy D. Bovelli Department of Cardiology, Santa Maria Hospital, Terni, Italy G. Di Tano Department of Cardiology, Ospedale Civile, Cremona, Italy G. Alunni Á S. Gori Department of Cardiology, Ospedale S.M. della Misericordia, Perugia, Italy P. Faggiano Department of Cardiology, Spedali Civili, Brescia, Italy L. Tarantini Department of Cardiology, ‘‘S. Martino’’ Hospital of Belluno, Belluno, Italy 123 Intern Emerg Med (2012) 7:439–446 DOI 10.1007/s11739-012-0794-9