In a paper published today, Professor Reis-Filho along with Dr Lajos Pusztai from the MD Anderson Cancer Center, Texas, USA have reviewed the progress made by gene expression profiling of breast cancers over the past decade.
The technique – measuring the expression of thousands of genes in cancer cells at once – has been critical in establishing that breast cancer is a collection of different diseases, each of which requires different treatments. For example, oestrogen-receptor (ER)-positive and ER-negative cancers are clinically completely different diseases.
“Gene expression analysis has changed the way breast cancer is perceived in that it is no longer regarded as a single disease,” Professor Reis-Filho says. “The technology has helped us to understand that different subtypes of breast cancer have completely different biology and require different treatment strategies.”
Traditionally, doctors decided women’s treatment based on clinical factors about their cancer, such as its location, tumour size and whether it had spread, as well as its ER status. These approaches have led to a steady reduction in breast cancer mortality rates over the past 30 years. However, using this approach, around 60 per cent of all patients with early-stage breast cancer were given chemotherapy after surgery, even though only two to 15 per cent would benefit and the rest were still at risk of side-effects.
Gene expression analysis had led to the development of multi-gene tests that give information about how the cancer will behave and help individualise patient treatment. For women with ER positive disease, there are tests – including one developed at The Institute of Cancer Research (ICR) called IHC4 – that can identify high risk patients who should receive systemic therapy, and other patients likely to have a good outcome who can avoid unnecessary chemotherapy.
Nevertheless, the use of these gene signatures to predict how women will respond to particular therapies is limited. Although some predictive tests have been developed, some have been based on unreliable data and their usefulness in patients remains controversial. One reason for this gap is that resistance to chemotherapy is complex, and standard gene expression profiling is unlikely to pick up the diverse and often subtle alterations that cause it.
“We still have some way to go before we achieve fully personalised medicine. There are still no commercially available molecular tests that can predict whether women will benefit from a specific therapy. For some disease subsets, such as ER-negative and triple negative disease, it is still not possible to give women an active prognosis or predict whether chemotherapy will be successful. However, a new technology called next generation sequencing should deliver new information that is likely to help us develop additional genetic tests,” Professor Reis-Filho said.
Several large international collaborations examining breast cancer genes are expected to sequence thousands of genomes over coming years using this technology, including the International Cancer Genome Consortium on breast cancer led by the Wellcome Trust Sanger Institute and involving the ICR.
These new research approaches should generate a wealth of new data that can be analysed to discover genetic abnormalities linked to cancer growth, spread and sensitivity to particular drugs. Combining this information with data drawn and theoretical and technical knowledge gained from gene expression analysis should ultimately lead to the development of new diagnostic and prognostic tests for breast cancer.
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Notes to editors:
Gene expression profiling in breast cancer: classification, prognostication, and prediction publishes in The Lancet, Volume 378, Issue 9805, Pages 1812 – 1823, 19 November 2011.
- Breast cancer is the most commonly diagnosed cancer in the UK – nearly 48,000 women and around 300 men are diagnosed every year
- One in eight women in the UK will develop breast cancer at some point in their lifetime
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