c-erbB-2 in breast cancer.

Abstract

Over the last few years a lot of research has been carried out regarding the onset, progress and relapse of cancer. Statistical data show that breast cancer is the most common disease that afflicts the human female population. The Malta National Cancer Registry (2002) states that breast cancer is one of the most common cancers diagnosed in the Maltese female population with a high mortality rate up to 90 deaths yearly. Several genes and their products have been identified over the last years. Some of these play an active role in the development and progression of breast cancer. These genes are known as Proto-oncogenes and c-erbB-2 is one of these (Gullick et al., 1987). c-erbB-2 is also known as Her2/neu. This gene resides on chromosome 17 band 21q-22q locus 1 (Yamamoto et al., 1986). Slamon (1987) in one study reported that 26% of 189 breast cancers showed amplification of c-erbB-2 protein, which is said to be a growth factor receptor protein. Various factors are known to affect the survival of breast cancer patients. Patients with c-erbB-2 overexpression have been found to have a poorer prognosis. Worse still are the patients with gene amplification as these have an increased chance of relapse (Slamon et al., 1987). Other factors which, in conjunction with c-erbB2 over expression, affect the prognosis, are the type of cancer, node involvement, nuclear grading and cell markers (Wright et al., 1989). Patients diagnosed with breast cancer have a better chance of survival thanks to the availability of a variety of modem therapies such as chemotherapy, radiotherapy, hormonal therapy and surgery. In the case of c-erbB-2 positive patients Herceptin (Trastuzumab )monoclonal antibody therapy is used. Through unique action mechanisms, Herceptin specifically targets the persistant, aggressive nature of c-erbB-2 driven metastatic breast cancer (Sliwkowski et al., 1998). This increases the survival rate of such patients. HER2/neu amplification and overexpression are tested using either Fluorescence Insitu Hibridization or Immunohistochemistry techniques. Testing for HER2 is important to establish those patients with breast cancer who would obtain some benefit with the use of Herceptin therapy. Herceptin is a monoclonal antibody, which through it unique mechanisms of action targets the aggressive nature of the HER2 driven metastatic breast cancer (Sliwkowski et al., 1999). These mechanisms include two cytotoxic mechanisms such as potentiation of chemotherapy and facilitating immune function and a cytostatic action by inhibiting tumour cell proliferation (Pietras et al., 1994; Pegram et al., 1999; Sliwkowski et al., 1999). The aims of this study are: 1. Prevalance of c-erbB-2 positivity in the Maltese female breast cancer population. 2. To compare c-erbB-2 in cancerous tissue sections, according to tumour grade, age, node involvement and oestrogen/ progesterone status. 67 cases of invasive breast carcinoma will be reviewed and representative blocks will be chosen to be stained for c-erbB-2. Staining patterns will be assessed by the study pathologist. Using statistical analysis the results obtained will be correlated in relation with age/menopause of the patients, tumour grade, Oestrogen/ progesterone status and lymph node involvement.