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Background/aim: Two effective cytotoxic agents, doxorubicin and trastuzumab, are associated with potentially life-threatening cardiotoxicity. The present study was designed to investigate cardiotoxicity aggravated by the timing of administration of trastuzumab and doxorubicin in rats., Materials and Methods: Twenty-four rats were randomly assigned to one of four groups. These received one of the following treatment drug regimens administered via intraperitoneal injection: (i) 0.9% saline control (n=6); (ii) doxorubicin (5 mg/kg) on day 1 then trastuzumab 10 mg/kg on day 15 (n=6); (iii) trastuzumab 10 mg/ kg on day 1 then doxorubicin (5 mg/kg) on day 15 (n=6) or (iv) doxorubicin (5 mg/kg) on day 1 and trastuzumab 10 mg/ kg on day 1 (n=6). On the 30th day, the hearts were processed for pathological analysis by electron microscopy., Results: Electron microscopy revealed an ultrastructurally normal heart tissue in the control group. At electron microscopic examination of the tissue samples in the second and fourth group, a mild degree of dilation was observed in the peri-nuclear cisternae of some heart muscle cells. In the third group, pathological changes were detected in mitochondria. These exhibited prominent cristae, which also showed a mild degree of ultrastructural pathology in mitochondria., Conclusion: Based on electron microscopy findings, sequential administration of anthracycline first, followed by trastuzumab is safer in terms of cardiotoxicity, while the most toxic schedule for the rat heart was trastuzumab first, followed by anthracycline., (Copyright© 2015 International Institute of Anticancer Research (Dr. John G. Delinassios), All rights reserved.)

Introduction: Trastuzumab is the first anti-HER-2 humanized monoclonal antibody. The benefit of adjuvant trastuzumab has been shown in randomized phase III trials. Despite trastuzumab being recommended for 52 weeks in the adjuvant treatment of HER-2 positive breast cancer according to the current breast cancer guidelines, there is still no consensus on the optimal duration of adjuvant trastuzumab. The aim of our study is to investigate the efficacy and safety of adjuvant trastuzumab for 9 weeks and 52 weeks in axillary lymph node positive HER-2 positive breast cancer patients., Patients and Methods: A total of 271 HER-2 and axillary node positive breast cancer patients who received trastuzumab in adjuvant treatment between the years 2005 and 2013 were retrospectively analyzed. Patients with axillary node positive HER-2 positive breast cancer who were non-metastatic were enrolled to the study. Patients were allocated to the 9 week trastuzumab group (n = 155) or the 52 week trastuzumab group (n = 116). Kaplan-Meier survival analysis was carried out for disease free survival (DFS) and overall survival (OS). Two-sided p values of <0.05 were considered statistically significant. The most important limitation of our manuscript is the retrospective design., Results: The median follow-up time for this analysis was 34 (4-95) months. Patients' clinical and pathological characteristics were well balanced between the two treatment arms. In the 9 week trastuzumab treatment group, the DFS rate was 96.7%, 84.8% and 74.9% in the first, third and fifth years respectively, whereas in the 52 week trastuzumab treatment group it was 94.3%, 80.0% and 80.0% (P = 0.76). In the 9 week trastuzumab treatment group, the OS rate was 99.3%, 92.2% and 88.3% in the first, third and fifth years respectively, whereas in the 52 week trastuzumab treatment group it was 99.0%, 94.7% and 78.6% (P = 0.99). In both groups, symptomatic heart failure was not reported but asymptomatic left ventricular ejection fraction (LVEF) decline was observed 3 (1.9%) and 18 (15.5%) patients in the 9 week and 52 week trastuzumab treatment groups, respectively (P < 0.001)., Conclusion: In our study, the efficacy of trastuzumab for 52 weeks and 9 weeks was similar in node-positive HER-2 positive breast cancer. Cardiotoxicity was significantly increased in the 52 week trastuzumab arm compared to the 9 week trastuzumab arm.

Bevacizumab is a recombinant humanized monoclonal antibody that selectively blocks the activity of vascular endothelial growth factor (VEGF) receptor and it is used in metastatic colorectal patients. We present here a case of fatal necrotizing fasciitis in a patient during bevacizumab treatment for colorectal cancer. In our review of the literature, necrotizing fasciitis was not reported before or during bevacizumab treatment.

Background: Trastuzumab emtansine (T-DM1), a novel drug developed for the treatment of HER2-positive breast cancer, is a human epidermal growth factor receptor (HER2) targeted antibody drug conjugate, composed of trastuzumab, a stable thioether linker, and the potent cytotoxic agent DM1 (derivative of maytansine). It has been shown that, in preclinical studies, it has anti-tumor activity in trastuzumab refractory cancer cells. In this review, we aim to show the clinical data about trastuzumab-DM1 (T-DM1) therapy and to discuss the therapy advantages for the management of patients with HER2-positive breast cancer., Scope: T-DM1 showed positive results in clinical studies of HER2-positive metastatic breast cancer. PubMed database, ASCO and San Antonio Breast Cancer Symposium Meeting abstracts were searched up to September 2012 by using the terms 'trastuzumab emtansine (T-DM1) and anti-HER2 treatment'; papers which were considered relevant for the aim of this review were selected by the authors., Findings: The phase III randomized trial EMILIA has shown that T-DM1 provided objective tumor responses and significantly improved progression free survival and overall survival compared to lapatinib and capacitabine combination in HER2-positive metastatic breast cancer patients treated with a prior taxane and trastuzumab regimen. It is believed that T-DM1 will play a role in the management of patients with advanced and early stage HER2-positive breast cancer, but this awaits further study. In particular, the ongoing phase III trials MARIANNE and TH3RESA will further give information about the place of T-DM1 in the treatment algorithms for HER2-positive disease., Conclusion: The trials of T-DM1 as a single agent and in combination with other chemotherapies have shown clinical activity and a favorable safety profile in patients with HER2-positive metastatic breast cancer. There are ongoing studies of T-DM1 showing an increasing tendency towards moving the study of these agents to earlier stages of HER2-positive breast cancer.

Background: Lack of response in some patients and relapse during the course of therapy in the treatment of HER2-positive early breast cancer and metastatic breast cancer continue to challenge researchers and clinicians towards a better understanding of the fundamental mechanisms of trastuzumab action and new therapies for HER2. The aim of this review is to discuss current and future treatment options with pertuzumab in the light of new insights into HER2-positive breast cancer., Scope: Pertuzumab showed positive results in clinical studies and agents in routine clinical usage are updated. The PubMed database, ASCO and San Antonio Breast Cancer Symposium Meeting abstracts were searched up to June 2012 by using the terms 'pertuzumab' and 'anti-HER2 treatment'; papers which were considered relevant for the aim of this review were selected by the authors., Findings: The presented trials of phase II and phase III randomized trials of CLEOPATRA, NEOSPHERE and TRYPHAENA have showed pertuzumab action to be complementary to trastuzumab without increasing adverse events. Adding pertuzumab to trastuzumab in the first line of HER2-positive metastatic breast cancer and in the neoadjuvant treatment of locally advanced HER2-positive breast cancer is usually well tolerated. The evaluation of health-related quality of life showed that combining pertuzumab with docetaxel and trastuzumab compared to placebo have no detrimental effect with adding pertuzumab., Conclusion: Pertuzumab is the first HER dimerization inhibitor with a mechanism of action complementary to trastuzumab. Studies with anti-HER2 combination treatments indicate that the use of more than one HER2-targeted therapy was superior to one of these agents alone. Pertuzumab has produced impressive anti-tumor activity in combination with trastuzumab. There are ongoing studies with pertuzumab with an increasing tendency towards moving the study of these agents to earlier stages of the disease, namely in the adjuvant and neoadjuvant setting.

Human epidermal growth factor receptor (HER) 2 overexpression, observed in 20-25 percent of invasive breast cancers, is well known to be associated with a more aggressive phenotype and poor prognosis, with resistance to certain chemotherapeutic agents. The majority of patients with metastatic breast cancer who initially respond to trastuzumab, demonstrate disease progression within 1 year of treatment initiation. Furthermore, lack of response in some patients and relapse during the course of therapy, continue to challenge researchers and clinicians. A better understanding of the fundamental mechanisms of trastuzumab action is required so that new therapies directed at HER2 can be developed. We present here findings for mechanisms, both of Trastuzumab action and clinical resistance or escape.