Anti Her2 Therapy. clinical trials

Cardiotoxicity in Metastatic Her 2 Positive Patients Treated With Trastuzumab ,Pertuzumab and Taxanes

Approximately 15-25% of all breast cancers are human epidermal growth factor receptor 2 (HER2) positive and it has been well known that HER2 overexpression is associated with more aggressive phenotype and poor prognosis with resistance to certain chemotherapeutic agents. Trastuzumab administration as an adjuvant and in metastatic HER2 positive breast cancer is associated with both symptomatic and asymptomatic cardiotoxicity. The incidence of trastuzumab-mediated cardiotoxicity were 27% with antracycline combination and 13% when it was administered with paclitaxel . Pertuzumab, a recombinant humanized monoclonal antibody binding to the HER2 dimerization domain, prevents dimerization of HER2 with other HER receptors (HER3,HER1, and HER4) especially with HER3. Blocking HER2-HER3 dimerization is postulated to be the most clinically relevant action of pertuzumab and this can effectively block her2-mediated cell signaling. Pertuzumab is indicated in combination with trastuzumab and docetaxel for the treatment of patients with HER2-positive metastatic breast cancer who have not received prior anti-HER2 therapy or chemotherapy for metastatic disease. Treatment of breast cancer with pertuzumab plus trastuzumab plus docetaxel as first line treatment until disease progression might be complicated by cardiotoxicity in up to 14.5% of the Patients. Cardinale et al showed that troponin I (TNI) positive identifies trastuzumab-treated patients who are at risk for cardiotoxicity and are unlikely to recover from cardiac dysfunction despite HF therapy. There is very little data about the reversibility and identification of patients at risk for cardiotoxicity of the pertuzumab plus trastuzumab plus docetaxel regimen and of those who will not recover from cardiac dysfunction,this information is crucial. The usefulness of troponin I (TNI) and Brain natriuretic peptide (BNP) in the identification of patients at risk for PT cardiotoxicity and in the prediction of LVEF recovery has never been investigated. based on this background , this study aim is to evaluate the cardiotoxicity of pertuzumab plus trastuzumab plus docetaxel regimen and the application of troponin I (TNI) and Brain natriuretic peptide (BNP) in this setting.