Monday 4 February 2008
Scientists at the Breakthrough Breast Cancer Research Centre at The Institute of Cancer Research in London have identified how some breast cancers may become resistant to hormone treatments like tamoxifen. The study*, published in the February issue of the scientific journal Cancer Cell, shows for the first time that a protein called CDK10 is able to control the development of tamoxifen resistance in hormone sensitive breast cancer and has potentially important implications in the treatment of women with this form of the disease.
It is estimated that around 75% of breast tumours are hormone sensitive and use the female hormone oestrogen to grow. Tamoxifen and other anti-oestrogen drugs are a key treatment for women with this type of breast cancer because it reduces the ability of breast cancer cells to use oestrogen to grow, helping to prevent the disease spreading to other parts of the body or returning, and controlling tumours that have already spread. Tamoxifen can work extremely well for many women and has had a major impact on breast cancer survival. However, over time some patients' tumours become resistant to tamoxifen.
Professor Alan Ashworth, Director of the Breakthrough Breast Cancer Research Centre, says; "Some hormone sensitive breast cancers will eventually become resistant to tamoxifen and this is the major reason why cancer may return. Research to understand why this happens is vital if we are to develop ways to overcome it for the benefit of patients."
To develop a better understanding of how this might occur, Professor Ashworth, Dr Christopher Lord and colleagues at the Breakthrough Breast Cancer Research Centre used a sophisticated screening method to identify genes that, when suppressed, cause tamoxifen resistance. The researchers identified Cyclin-Dependent Kinase 10 (CDK10) as a critical component in determining cancer cells' response to tamoxifen and other hormone therapies.
Importantly, the researchers also found that patients with low levels of CDK10 in their tumours were less likely to benefit from tamoxifen treatment - their cancers were more likely to return, and they tended not to survive for as long as women whose tumours produced higher levels of the molecule. They also uncovered important information on how this might occur - showing that a process called methylation may to be critical to 'switching off' CDK10 levels inside breast cancer cells.
Professor Alan Ashworth adds; "Drug resistance is a serious problem for women with breast cancer. It's devastating for a patient to see their cancer return because of resistance, especially after enduring a long course of treatment and after a long period of remission. Through this work, we've identified some of the factors that control this effect and in the future we may be able to use this information to decide which treatments to give to patients to avoid resistance."
This research is just one example of the groundbreaking work taking place at the Breakthrough Breast Cancer Research Centre at The Institute of Cancer Research, Europe's leading cancer research centre. One area of the centre's work is to identify genetic changes that take place in breast cancer cells and use this knowledge to benefit patients in the clinic.
Breakthrough Breast Cancer needs to raise at least £25 million each year for the next three years to support its vital research, campaigning and education work. For more information about Breakthrough Breast Cancer, please visit www.breakthrough.org.uk.
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For further information please contact:
The Institute of Cancer Research
0207 153 5359 / 07721 747900
Notes to editors
* “Identification of CDK10 as a novel determinant of resistance to endocrine therapy for breast cancer” by Elizabeth Iorns, Nicholas C. Turner, Richard Elliott, Nelofer Syed, Ornella Garrone, Milena Gasco, Andrew N. J. Tutt, Tim Crook, Christopher J. Lord and Alan Ashworth.
- Most breast tumours contain receptors for the female hormones oestrogen and progesterone and are dependent on these hormones for their growth and survival. Drugs that target this characteristic, such as tamoxifen and anastrozole (Arimidex), have had a major impact on breast cancer survival rates. These treatments interfere with the ability of cancer cells to respond to hormones and, as a result, kills the tumour whilst leaving healthy tissues relatively unharmed.
- Tamoxifen can reduce the risk of breast cancer returning by about 30 per cent. On average it has been shown to reduce the risk of developing a second breast cancer by about 50 per cent. Tamoxifen also reduces the risk of heart attacks, and it slows down the process of osteoporosis (thinning of the bones) in postmenopausal women.
- At the Breakthrough Breast Cancer Research Centre at The Institute of Cancer Research in London, scientists led by Professor Alan Ashworth investigated the resistance of breast cancer to tamoxifen by studying 779 molecules inside breast cancer cells grown in the laboratory. The scientists used an innovative and powerful technique – called High Throughput RNA Interference Screening – to detect genes that, when suppressed, could cause resistance to tamoxifen.
- The researchers discovered that CDK10 normally suppresses a cell growth pathway, and when CDK10 is absent, the suppression is lifted. The pathway does not involve oestrogen or the oestrogen receptor, and therefore allows cancer cells to grow in the presence of tamoxifen.
- The scientists confirmed the relevance and importance of this result by studying cancer samples and medical records from over 100 women treated with tamoxifen. They found that low levels of CDK10 were linked to the cancer returning more quickly following treatment, and survival times were shortened.
- This research was funded by Breakthrough Breast Cancer and the Tertiary Education Commission of New Zealand.
Breakthrough Breast Cancer
- Breakthrough Breast Cancer is the UK’s leading charity committed to fighting breast cancer through research, campaigning and education. Our essence comes from the thousands of people who are committed to a single vision - to work for a future free from the fear of breast cancer. More information can be found at: www.breakthrough.org.uk or through the Breakthrough Information Line 08080 100 200.
- The Breakthrough Toby Robins Breast Cancer Research Centre is situated in the Mary-Jean Mitchell Green Building at the Chester Beatty Laboratories at The Institute of Cancer Research. It is the first dedicated breast cancer research facility in the UK and, under the directorship of Professor Alan Ashworth, its 120 scientists and clinicians are working on a programme of cutting-edge biological research to discover the causes of breast cancer, find methods of prevention and develop new treatments and more effective methods of diagnosis.
- During 2008, Breakthrough Breast Cancer will open three new research units in Edinburgh, Manchester and London to investigate ways to prevent breast cancer and improve diagnosis and treatments for the disease. They will complement existing research currently being undertaken at the Breakthrough Breast Cancer Research Centre.
The Institute of Cancer Research
- The Institute of Cancer Research is Europe’s leading cancer research centre with expert scientists working on cutting edge research. It was founded in 1909 to carry out research into the causes of cancer and to develop new strategies for its prevention, diagnosis, treatment and care. Website at: www.icr.ac.uk.
- The Institute works in a unique partnership with The Royal Marsden NHS Foundation Trust, forming the largest Comprehensive Cancer Centre in Europe. This relationship enables close daily contact between research scientists and those on the frontline in the fight against cancer - the clinicians, the carers and most importantly, the patients.
The Institute is a charity that relies on voluntary income. The Institute is one of the world’s most cost-effective major cancer research organisations with over 90p in every £ directly supporting research.
- Breast cancer is now the most common cancer in the UK, accounting for nearly 1 in 3 of all female cancers.
- Over 44,000 women are diagnosed with breast cancer every year in the UK and 1,000 women will die every month from this disease.