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Breast cancer and genes.

The management of breast cancer depends on the type of tumour and its size or spread at discovery, but there are other markers of the aggressiveness, tumourigenic capacity or invasiveness. These characteristics are now being identified by studying the tumour's genetic profile. This process, using microarray RNA probes and polymerase chain reactions for gene profiling, allows the tumour's fingerprint or its invasiveness gene signature to be established.

Particular genes are found more or less commonly in each tumour and each one's prevalence is called its expression. Seldom is a single gene over-expressed to give a tumour its aggressive characteristics, but rather a set of hundreds of genes whose combined expression gives clues to its invasiveness.

One exceptional gene in breast cancer is the HER2 growth factor gene, which is over-expressed in about 20% of all breast tumours and is associated with a poor prognosis. This has attracted publicity because the drug company Roche has produced a human monoclonal antibody against a particular domain of the gene which is proving an effective but controversial addition to treatment. The antibody is trastuzumab (Herceptin), and the latest report after a 2-year follow-up has now been published (Smith et al., Lancet 2007; 309: 29-36).

It is controversial in that it is very expensive; it is only used in patients who have early HER2-positive disease; it has side-effects; and the long-term effects of monoclonal antibody therapy are not known. It is given after surgery, radiotherapy and/ or chemotherapy every 3 weeks for at least 1 year. This is a formidable regimen against an aggressive tumour but the results are significant, with those receiving Herceptin having a hazard ratio for the risk of death of 0.66 compared with observation alone after 2 years of follow-up.

Generally, though, most information about a tumour is derived from measuring the expression of a set of its genes rather than a single gene. Which genes are present and the degree of their expression gives each neoplasm its invasiveness genetic signature.

This term invasiveness genetic signature (IGS) was coined by Liu et al. (NEJM 2007; 356: 217-226), who looked at the expression of 186 genes in breast cancer tumours and matched them to outcomes. They found it was not only the over-expression of some genes but the under-expression of others that was linked to invasiveness.

It has been a formidable task to identify which genes to check and how to link each to a positive or negative influence of invasiveness. The exact genes measured may change with experience, but the authors' results showed high correlations between each tumour's IGS and the woman's clinical outcome. They stratified the tumours into two groups according to their IGS and found 10-year metastasis-free survival rates were 81% in the good prognosis group, and 57% in the poor prognosis group. It also allowed them to identify 90% of patients in whom metastases would occur.

This is a major breakthrough in 'bench to bedside' research and moves us closer to delivering 'molecular staging' of malignancies.
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Title Annotation:THE BEST OF THE REST
Publication:South African Journal of Obstetrics and Gynaecology
Article Type:Clinical report
Geographic Code:6SOUT
Date:Apr 1, 2007
Previous Article:Breast density and cancer detection.
Next Article:Maternal exercise and fetal growth.

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