Authors

• Ivo Darko Gabrić — University Hospital Centre “Sestre milosrdnice”, Zagreb, Croatia — ORCID: 0000-0003-4719-4634
• Ljubica Vazdar — University Hospital Centre “Sestre milosrdnice”, Zagreb, Croatia — ORCID: 0000-0001-6264-3675
• Angela Prgomet — University Hospital Centre “Sestre milosrdnice”, Zagreb, Croatia — ORCID: 0000-0002-7830-8481

Keywords

cardiotoxicity, trastuzumab, reversibility

DOI

Full Text

**Purpose:** Cardiotoxicity is the most important side effect of trastuzumab, humanized monoclonal antibody to the HER2 protein, in use for immunotherapy of breast cancer. It is mainly manifested as a reduction in left ventricular contractility and the process is therefore mostly reversible. Temporary cessation of therapy often leads to recovery of cardiac function, and it is possible to continue the oncology treatment. (1-3) **Patients and Methods:** Since the beginning of 2009 until the end of 2015, we have analyzed 496 patients (pts) with non-metastatic breast cancer, treated with trastuzumab for one year with the standard adjuvant therapy protocol. Cardiotoxicity was defined with the reduction of left ventricular ejection fraction (LVEF) by 15% from the baseline or by 10% of normal values. Echocardiography was performed before the beginning and in three months period during therapy. If cardiotoxicity was established, pts were suspended from the trastuzumab therapy, with monthly echocardiography controls. **Results:** Cardiotoxicity was established in 54 pts (10.88%), most commonly in the first 6 months of starting treatment. Complete recovery of the cardiac function was found in 28 pts (51.85%) and they managed to finish trastuzumab protocol. Due to only partial recovery of the cardiac function or cardiotoxicity after readministration, trastuzumab therapy was not finished in 26 pts (48.14%). At the time when diagnosis of the cardiotoxicity were established average LVEF was 44.18% (20-52%). Pts with irreversible cardiotoxicity had significantly greater reduction of LVEF (15:27%, p<0.0001), higher mean serum level of NT-proBNP (134.7:92.3 ng/L, p=0.01) and in those pts trastuzumab was started earlier after prior chemotherapy (27:33.5 days, p=0.037). Only 6 pts had symptomatic moderate or severe heart failure. **Conclusion:** Trastuzumab cardiotoxicity occurs in about 10% of patients mainly in the first 6 months of therapy. It is more likely to be irreversible in pts with a more extensive decrease of the LVEF and a higher serum NT-proBNP level. The time between prior chemotherapy and administration of trastuzumab shorter than 30 days is more often associated with irreversible cardiac impairment.

Literature

1. Gabrić ID, Vazdar LJ, Pintarić H, Planinc D, Štefanović M, Trbušić M, et al. Risk factors for the occurrence and irreversibility of cardiotoxicity caused by trastuzumab therapy. Eur J Heart Fail. 2015;17 Suppl. 1:123.
2. Zamorano JL, Lancellotti P, Rodriguez Muńoz D, Aboyans V, Asteggiano R, Galderisi M, et al. Authors/Task Force Members; ESC Committee for Practice Guidelines (CPG); Document Reviewers. 2016 ESC Position Paper on cancer treatments and cardiovascular toxicity developed under the auspices of the ESC Committee for Practice Guidelines: The Task Force for cancer treatments and cardiovascular toxicity of the European Society of Cardiology (ESC). Eur J Heart Fail. 2016 Aug 27;•••: [Epub ahead of print]. https://doi.org/10.1002/ejhf.654
3. Gabrić ID, Vazdar L, Planinc D, Vinter O, Trbušić M, Bulj N, et al. Standard parameters on initial echocardiography cannot predict cardiotoxicity caused by trastuzumab. Eur Heart J Cardiovasc Imaging. 2013;14 Suppl 2:ii190.