1. Abstract Introduction  What is a Herceptin (Trastuzumab) ?  Herceptin (Trastuzumab) is an monoclonal antibody,it is an example of targeted therapy an agent that is directed against a specific change in the cancer cell. Herceptin is approved for the adjuvant treatment of HER2-overexpressing, node-positive or node-negative (ER/PR-negative or with one high-risk feature) breast cancer. __________________________ Methods Results Conclusion  The combination of Herceptin and chemotherapy decreased the death rate by 23 percent compared with chemotherapy alone.  After a median follow-up period of 29 months, women treated with a combination of either Herceptin plus doxorubicin (or epirubicin) and cyclophosphamide (AC therapy), or Herceptin plus paclitaxel (Taxol) survived on average more than five months longer than those treated with the chemotherapy drugs alone (25.4 months vs. 20.3 months).  Quality-of-Life Increases With Herceptin Use. Cardiac toxicity in the trial was 4.1 percent for those taking trastuzumab vs. 0.8 percent for those on standard chemotherapy  The most common adverse reactions in patients receiving Herceptin are fever, nausea, vomiting, infusion reactions, diarrhea, infections, increased cough, headache, fatigue, dyspnea, rash, neutropenia, anemia, and myalgiafevernauseadiarrheacoughheadachefatiguedyspnearashanemiamyalgia Adverse reactions requiring interruption or discontinuation of Herceptin treatment include CHF, significant decline in left ventricular cardiac function, severe infusion reactions, and pulmonary toxicity ventricularcardiac  2 years herceptin administration showed no better results in OS versa 1 year herceptin administration. Corresponding author and co-authors ; Gani Oruqaj; g_oruqaj@yahoo.com, mob; +377 44 23 77 42g_oruqaj@yahoo.com Learta Pervizaj ; learta1@hotmail.com,learta1@hotmail.com Lavdim Ibrahimi; filas_med@hotmail.comfilas_med@hotmail.com Fig.no.1 Normal HER2 expression HER2 amplification leads to HER2 overexpression HER2 overexpression leads to tumour proliferation Treatment with Herceptin r Extracellular targeting Herceptin, Omnitarg, cetuximab Signal transduction to nucleus Intracellular targeting Tarceva T, gefitinib Nuclear targeting antisense oligonucleotides, ribozymes Gene activation CELL DIVISION  HER2/neu (also known as ErbB- 2, ERBB2) stands for "Human Epidermal growth factor Receptor 2" and is a protein giving higher aggressiveness in breast cancers. It is a member of the ErbB protein family, more commonly known as the epidermal growth factor receptor family. HER2/neu has also been designated as CD340 (cluster of differentiation 340) and p185.ERBB2breast cancersErbBepidermal growth factor receptor familycluster of differentiation  An increased amount of HER2 is a marker for a very aggressive form of breast cancer. Approximately 30 percent of all breast cancers overexpress HER2.  The oncogene neu is so-named because it was derived from a cell line in rat. HER2 is named because it has similar structure to human epidermal growth factor receptor, or HER1. ErbB2 was named for its similarity to ErbB (avian erythroblastosis oncogene B), the oncogene later found to code for EGFRoncogeneepidermal growth factor receptor Targeting the HER receptor 1. Extracellular targeting 2. Intracellular targeting Aim of research; Trastuzumab q3w after standard adjuvant therapy 1 vs 2 years of treatment Adverse side events that often encounter during treatment Crossover permitted after 1st interim efficacy analysis Trial ;medical records of patients treated at the Cancer Clinic-ONKOMED IHC 3+ or FISH+ Node-positive and high-risk node-negative EBC Observation 1-year trastuzumab 2-year trastuzumab 8 mg/kg loading dose  6 mg/kg q3w Surgery + standard predefined (neo)adjuvant CT + RT Trial design AC, doxorubicin 60 mg/m 2 or epirubicin 75 mg/m 2 and cyclophosphamide 600 mg/m 2 HER2, human epidermal growth factor receptor 2; IHC, immunohistochemistry, MBC;metastatic breast cancer HER2-positive MBC (IHC 3 + or 2+) No prior chemotherapy for MBC AC q3w x 6 cycles (n=138) AC q3w x 6 cycles + trastuzumab 4 mg/kg loading, then 2 mg/kg qw until disease progression (n=143) Paclitaxel 175 mg/m 2 q3w x 6 cycles (n=96) Paclitaxel 175 mg/m 2 q3w x 6 cycles + trastuzumab 4 mg/kg loading, then 2 mg/kg qw until disease progression (n=92) Prior adjuvant anthracyclines (n 42) No prior anthracyclines (n 42) -OS, overall survival Probability of survival 17.9 24.8 +40% Trastuzumab + paclitaxel Paclitaxel 0 51010 1515 2020 2525 3030 3535 4040 4545 6.9 months 1.0 0.6 0.8 0.4 0.2 0.0 Trial : OS (IHC 3+ taxane subgroup) -Patients progressing on docetaxel alone could cross over to receive trastuzumab -FISH, fluorescence in situ hybridisation; -LVEF, left ventricular ejection fraction -Patients show a better outcome in overall survival rate in the regimen docetaxel + trastuzumab,8.5 months compared to paclitaxel + trastuzumab, 6.9 months HER2-positive MBC (IHC 3+ and / or FISH+) No prior chemotherapy for MBC Baseline LVEF >50% Docetaxel 100 mg/m 2 q3w x 6 cycles ( n 42) Docetaxel 100 mg/m 2 q3w x 6 cycles + trastuzumab 4 mg/kg loading, then 2 mg/kg qw until disease progression ( n 42) Twice as many patients receiving trastuzumab survived 3 years (33% vs 16%) Trastuzumab + docetaxel (n=92) Docetaxel alone (n=94) Patients alive (%) 22.731.2 0 20 40 60 80 100 05101520253035504045 +37% Time (months ) 8.5 months OS (IHC 3+ / FISH+)  a Based on pretreatment blood counts only  SAE, serious adverse event; H, trastuzumab;  Diff, difference SAE, % Fever Heart failure Leucopenia a Febrile neutropenia Alopecia Alone (n=95) 1 5 - 26 H (n=91) 2 6 - 26 Diff 1 0 Alone (n=94) 1 0 15 17 6 H (n=92) 1 20 23 10 Diff 0 1 5 6 4 Paclitaxel Docetaxel Effect of adding trastuzumab to chemotherapy: SAEs BREAST CANCER -HERCEPTIN IMPACT AND SUCCESS IN PATIENTS WITH AGGRESSIVE BREAST CANCER AND HER 2+ PROVED BY IHC OR FISH Gani Oruqaj, Learta Pervizaj, Lavdim Ibrahimi Armend Spahiu, MD, internist and medical oncologist KOSOVO, University of Prishtina-Prishtina, Medical Faculty, Cancer Care Clinic –ONKO-MED-Prizren,Kosovo FISH Patient tumour sample Herceptin ® therapy + – 2+2+ 3+3+ 1+0 + – FISH IHC Herceptin ® therapy Interceptors of HER signalling HER2 testing algorithm Methods and Material used in the trial to find out the HER 2 positivity in women with MBC. IHC and FISH confirm Patients alive (%) 22.731.2 0 20 40 60 80 100 05101520253035504045 +37% 8.5 months 1 year Trastuzumab trial 2 years Trastuzumab trial Acknowledgements ; Cancer Care Clinic –ONKO-MED, Prizren-Kosovo, Armend Spahiu, MD, medical oncologist, ONKO-MED