Herceptin® – from laboratory to cure in breast cancer? (page 1 of 8)
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Breast cancer remains the second most common cancer in the world (after lung cancer), and a major cause of cancer-related death in women. More than forty thousand new cases of breast cancer are diagnosed each year in the UK, and around 9% of women will develop the disease during their lifetime. Whilst there have been huge improvements over the past 20 years in the survival rate for women with early breast cancer (that which has not obviously metastasised at presentation), unfortunately around one third of all patients will develop recurrent disease despite primary treatment. For those who relapse in a site distant from the breast, the survival time has also improved, but only a minority will live for more than five years from the time of diagnosis of metastatic breast cancer.
HER2 positive breast cancer
In the 1980s, many laboratories worked on newly discovered oncogenes, amongst which were the Epidermal Growth Factor Receptor (EGFR) and the chicken erythroblastoma protein, c-erbB2. These were recognised to be part of a family of cell surface proteins whose intracellular portions function as tyrosine kinases, activated when the receptors dimerise, usually in response to ligand binding. The family is known as the human epidermal growth factor receptor family, and c-erbB2 or HER2 neu is now more widely known as HER2, and is over-expressed/amplified in about 20% to 30% of invasive human breast cancers.1 These so-called ‘HER2-positive’ breast cancers are an aggressive form of the disease with poor prognosis, including high risk of recurrence, metastasis and reduced overall survival.2
In the clinic, there are data to suggest that HER2 may also be an important predictive factor of response to chemotherapy and hormonal therapy in breast cancer.3 Therefore, testing to establish the HER2 status of tumours from women with breast cancer has been incorporated into routine clinical practice to assist prognosis and prediction of treatment response, and more recently, the possibility of using adjuvant Herceptin® . HER2 over-expression is usually caused by amplification of the HER2 gene,4 which leads to increased levels of HER2 mRNA and increased expression of the HER2 protein on the tumour cell surface.5 HER2 gene amplification occurs early in the development of breast tumours and is maintained throughout the course of the disease.
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