Irreversible cardiotoxicity after adjuvant treatment with trastuzumab in a case of breast cancer.

To the Editor: The debate about the cardiotoxicity of trastuzumab remains alive in the literature. In patients with human epidermal growth factor receptor type 2 (HER2) positive breast cancer, trastuzumab has significantly improved the overall survival and is the gold standard treatment in association with chemotherapy. Cardiotoxicity, expressed as a decrease in the left ventricular ejection fraction (LVEF), is not rare with trastuzumab: it occurs in 7% of patients when used as a single agent, peaking up to 27% when it is combined with anthracyclines. The cardiotoxicity is, however, usually reversible1. We describe the case of a 45-year-old woman with synchronous bilateral invasive breast cancer (right pT2N3aMx, left pT1cN0Mx), hormone receptor positive and HER2 positive, without evidence of metastases at staging tests. She underwent surgical therapy followed by adjuvant chemotherapy with doxorubicin plus paclitaxel (6 courses, standard dose) and radiotherapy to the thoracic wall, until December 2005. She started adjuvant therapy with letrozole 2.5 mg plus trastuzumab (loading dose 4 mg/kg, then 6 mg/kg every 3 weeks) in January 2006. Echocardiography at baseline and in January 2006 was normal (LVEF 55%). In April, asymptomatic myocardial dysfunction developed (LVEF 45%), with negative restaging tests. Trastuzumab was stopped and letrozole maintained. Two months later, the woman was admitted for heart failure. A computed angiotomography scan excluded pulmonary embolism, while echocardiography showed a dilated and severely hypokinetic left ventricle (LVEF 24%). She responded to standard therapy with furosemide, ramipril, carvedilol and an aldosterone antagonist. An echocardiogram 2 weeks later showed an apical thrombus and treatment with warfarin was started. During the following months, she remained eupneic at rest, with persistent sinus tachycardia. In August the LVEF was 20%; a total body positron emission tomography/computed tomography scan showedno signsof cancer. At follow-up5months later, the heart function did not show any improvement despite full cardiac therapy. She received an implantable cardioverter defibrillator. Tumori, 94: 777-778, 2008