Increasing understanding of the human genes responsible for cancer cell growth has led to a new phase of breast cancer treatment. A targeted approach to treating breast cancer involves the use of monoclonal antibodies. A monoclonal antibody is a synthetic protein that has been designed to target specific cancer cells in the body.

Herceptin (trastuzumab) is the first of this class of drugs to be approved for clinical use. Herceptin works by blocking the function of HER2 a specific cancer gene associated with aggressive breast cancer cell growth.

Furthermore, it only targets cancer cells, leaving healthy cells unharmed. HER2 is a member of the Epidermal Growth Factor receptor family that is strongly overexpressed in about 20-30% of metastatic breast cancer patients. Researchers have determined that the overproduction of HER2 contributes to the uncontrolled growth of cells, which is the hallmark of cancer. Patients with this condition are said to be HER2-positive. For this reason, accurate diagnostic assessment of HER2 is essential for the effective treatment of metastatic breast cancer.

Results to be published in the April issue of the Journal of Pathology indicate that FISH (fluorescence in situ hybridisation) testing has many advantages over other methods. However, in the UK, there are very few diagnostic laboratories with the expertise to carry out the test. Researchers would like to see wider implementation of FISH testing.

Whilst many methodologies for HER2 testing have been reported in the literature, only two techniques are commonly used: immunohistochemistry (IHC) and FISH which estimate protein expression and gene amplification respectively. IHC is widely used in many laboratories but its results are dependent on the subjective interpretation of staining so the findings can be variable due to observer bias. The IHC test uses a 0 to 3+ scoring system, and those patients in the 2+ and 3+ are thought to benefit from Herceptin.

Researchers from three institutions - Glasgow University, Royal Marsden Hospital, London, and Nottingham City Hospital - studied 426 samples from 37 hospitals across the UK to look for correlation between the IHC and FISH analyses results.

The researchers including Dr John Bartlett of the University of Glasgow found that for samples that were classified as IHC 0/1+ negative or IHC 3+ positive, there was good correlation with the FISH results.

However, amongst the IHC 2+ tumours only 48% of the tumours were also FISH positive. This means that for 52% of the tumours the IHC test indicates that they would benefit from treatment with Herceptin whereas the FISH results show that they would not benefit from the treatment.

Current guidelines recommend that all IHC 2+ samples are checked by both IHC and FISH and according to John Bartlett, 'Our results indicate that the performance of FISH on the IHC 2+ group is necessary for accurate determination of HER2 positive tumours. This builds on previous work from our group which, in line with current world literature, suggests that FISH provides a better predictive test for identification of HER2 overexpressing patients and those most likely to respond to Herceptin.

He added, 'Although FISH has been shown to be effective, its application remains limited by the small number of centres where expertise is available. There is a strong case to be made for wider implementation of FISH testing to determine HER2 status in breast cancer and this needs to be accompanied by better training and quality assurance schemes.'

Media Relations Office (media@gla.ac.uk)

To obtain a full copy of the article ,please contact Joanna Gibson on 01243 770674 or e-mail jgibson@wiley.co.uk To arrange an interview with Dr Bartlett, please call the University Press Office on 0141 330 3535 / 3683.

First published: 4 March 2003