Herceptin Essay

Oncogenes were discovered in the 1960s, when it was discovered that some animal cancers such as lymphomas were caused by viruses. Some of these viruses were notable due to the simplicity of their RNA genome. These viruses only had three distinct transcription units, involved in the replication of the virus (coat proteins and reverse transcriptase etc.), and an extra gene. This was an oncogene. When oncogenes are properly functioning they are termed proto-oncogenes (Todd R, 1999). Their normal function is to control cell proliferation. These function in growth signalling pathways, and conversely to tumour suppressing cells are activated through a gain in function rather than a loss of it. This occurs in two ways, by producing more of a product, or producing a subtly different product, as a result of a mutation similar to tumour suppressor genes (Croce, 2008). Oncogenes play a particularly strong role in the development of breast cancers. Often the normal ERBB2 and other related genes are amplified in late stage neuroblastomas and rhabdomyosarcomas. ERBB2 encodes HER2 which is a member of the epidermal growth factor

The same treatment is not used for all types of breast cancers because these cancers differ in many ways and will respond differently to treatments. There is no known treatment that will help all four types of cancer.

Cancer is the uncontrollable division and growth of abnormal cells resulting in formation of an aggressive tumour. In some forms of Breast cancer, the cells proliferate uncontrollably due to over-expression of the protein HER2 (Human Epidermal Growth Factor Receptor 2); a receptor embedded within the membrane of cells, allowing for the transfer of signals outside to inside the cell. Trastuzumab is a monoclonal antibody administered through intravenous infusion, to be taken on its own or in combination with one or more chemotherapy regimens. It reduces risk of the cancer reoccurring or spreading by inhibiting the effects of HER2, and enhancing the body’s immune system.

HER2 status. Logistic and ordinal regression analyses in addition to likelihood ratio test were used to explore

As the cells change, it begins to divide rapidly causing a tumor to form. The term “breast cancer” refers to a malignant tumor that has developed from cells in the breast. Breast cancer can begin in different areas of the breast, or in some cases, the tissues in between. There are many different types of breast cancer, including non-invasive, invasive, recurrent, metastatic breast cancer, as well as the intrinsic or molecular subtypes of breast cancer. Human epidermal growth factor receptor 2 (HER2) is overexpressed in around 20-30% of breast cancer tumors. It is associated with a more aggressive disease, higher recurrence rate, and increased mortality.

Herceptin (trastuzumab) is a therapeutic monoclonal antibody, which is specifically designed to target HER2 (human epidermal growth factor 2) receptors found on breast cells( Tan, 2010) . HER2 is a receptor protein that is a member of the epidermal growth factor receptor family and is over expressed in approximately 10-20% of breast cancers that have amplification of the HER2 gene (Jatoi, et al., 2010). Herceptin has been found to selectively apply anti-tumor effects in cancer models and patients with HER2+ breast cancer (Gajria & Chandarlapaty, n.d.). Although all normal breast cells present HER2 receptors on their surface, some cells may express more receptors, as high as two million receptors per cell (Vu & Claret, 2012), due to a mutation causing over expression of the HER2 gene. As a result of the increased number of HER2 receptors on the surface of breast cells, more hormones will bind and increased signals are given off, causing the cells to divide quicker and more frequently, resulting in HER2 positive breast cancer.

Materials and Methods Patients In this retrospective study, performed across 4 oncology centers in Saudi Arabia and Egypt, we evaluated 280 women who were diagnosed with unilateral early breast cancer from between March 2010 and October 2013. Patients received standard neoadjuvant chemotherapy (6-8 cycles of an anthracycline and Ttaxane-containingregimen) with or without trastuzumab according to the human epidermal growth factor receptor 2 (HER2) status. After excluding patients who underwent breast conservative surgery because of a possible high incidence of recurrence, the included patients underwent modified radical mastectomy with axillary clearance followed by local radiotherapy with/without hormonal treatment for Candide patients,

PREDICTORS OF PATHOLOGIC RESPONSE TO TRASTUZUMAB-BASED NEOADJUVANT TREATMENT IN A CONSECUTIVE MONOINSTITUTIONAL SERIES OF BREAST CARCINOMAS TESTED WITH FRONTLINE DUAL-COLOR HER2 FISH

The human epidermal growth factor receptor-2 (HER-2)/neu, (erbB-2) gene is localized to chromosome 17q and encodes HER2, is a 185 kDa protein (p185) and 1255 amino acids with an intracellular tyrosine kinase domain and an extracellular ligand binding domain. However, HER family is dysregulated and/or show abnormal signaling activity in a broad range of human tumors and, in particular, the HER2 receptor plays a critical role in disorders. The primary cause of HER2 overexpression in cancers is the amplification of the HER2 gene, an event rarely identified in other malignancies. The essential role of HER2 in the HER signaling cascades leads to the development of anti-HER2 monoclonal antibodies (mAbs) for cancer therapy. In particular, the humanized

from the amino acid tryptophan. This neurotransmitter is produced and released by serotonergic neurons in the brain and intestines, and it can also be found in the bowels and blood platelets. Researchers believe that it’s contributing to our mood, self-confidence, sleep, sexual activity, emotions and appetite. (1)

According to the American Cancer Society, Each year, more than 200,000 women are diagnosed with breast cancer; furthermore Twelve percent of all women will contract the disease, and 3.5% of them will die from breast cancer (American Cancer Society, 2005). There are risk factors that may lead to breast cancer. There are 4 stages of breast cancer and several treatments, although treatments vary from types and stages of breast cancer. Breast cancer is the leading cause of death among women who are 40 to 55 years old (Breast Cancer, 2009).Cancer occurs when cells divide uncontrollably. It changes from a normal cell to cancerous cells that require gene alterations. Therefore the altered genes and the uncontrolled growth may lead to tumors.

2.43 at the first day to 0.88 μg/1 g tissue at the end of the end of the

According to Chen Xu et al,they were the first to compare HER2 expression using two tumour containing blocks with the use of all primary tumour blocks.

On comparing our results with reports in the literature that utilized technical methods other than IHC; Sáez et al. [14] using western blot analysis found that approximately 25% of the HER2-overexpressed BC patients express p185HER-2 and p95HER-2 receptors. Kallergi et al. [28] examined the expression of truncated HER2 on circulating tumor cells of BC patients using a triple-staining immunofluorescent method and recorded 11.1% and 39.1% p95HER2-positive rate for early and metastatic patients respectively. Christianson et al. [26] recorded 22.4% of BC tissues expressing p95HER2 with using western blotting and immunoprecipitations technique. Duchnowska et al. [24] using quantitative assessment of p95HER2 expression found that 33% of metastatic BC patients treated with trastuzumab were p95HER2 positive. Molina et al. [17] had reported 26.7% and 45.7% p95HER2 positivity rates in the primary HER2-positive

Antibody therapy can be used in a variety of ways to treat cancer. As described above, they may act through ADCC or CDC. An alternative approach is to conjugate the monoclonal antibody to a toxin, a cytotoxic agent, or a radioisotope. With