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Discovery has potential to boost tamoxifen's effectiveness

15 October 2010 Association for International Cancer Research

SCIENTISTS in London have found a potential new way of boosting the effectiveness of the anti-breast cancer drug, tamoxifen.

The work carried out by Professor Clare Isacke and her team at the Breakthrough Breast Cancer Research Centre at The Institute of Cancer Research (ICR), and partly funded by AICR (Association for International Cancer Research) could open the door to new treatments for those who have developed a resistance to tamoxifen, and has been described as an important new discovery.

Many breast cancers require the female sex hormones oestrogen and progesterone. Described as: ‘hormone sensitive’ or ‘hormone receptor positive’ they can be treated with drugs that block the effects of oestrogen and progesterone, such as tamoxifen.

Tamoxifen is given to most women for five years after they are first diagnosed with breast cancer to help prevent the disease recurring.

However, some breast cancers are resistant to the drug, or can develop resistance over time, allowing the cancer to recur or continue growing. Professor Isacke’s discovery could lead to new drugs that counteract this resistance.

AICR's Scientific Co-ordinator Dr Mark Matfield, explained that resistance to treatment is a major problem for cancer patients.

“These findings are an exciting and important new discovery, as they could potentially help in the development of new treatments for women who have become resistant to tamoxifen,” he said.

More than a million women worldwide, are diagnosed with breast cancer every year, accounting for a tenth of all new cancers and nearly a quarter of all new female cancer cases. In the UK alone, breast cancer is now the most common cancer: in 2007 almost 45,000 women – and 277 men – were diagnosed with the disease.

Tamoxifen, developed more than 30 years ago to treat breast cancer, prevents oestrogen from stimulating the growth of breast cancer cells. It is prescribed for women who are ER positive. That means that oestrogen receptors (ER) have been found on their breast cancer cells. The oestrogen receptor is the part of the breast cancer cell that oestrogen attaches itself to, triggering a chain of events which can lead to the cell growing and dividing in an uncontrolled manner and forming a tumour.

Work from Professor Isacke’s team, funded by AICR and Breakthrough Breast Cancer, focuses on situations where, even when oestrogen is not present, the oestrogen receptor can become activated.

In their current paper, published in leading cancer journal Oncogene, they show that when a protein called RET is switched on, it can activate the oestrogen receptor in the absence of any oestrogen.

To confirm their findings from the laboratory, they took tissue samples from oestrogen positive breast cancer patients and found that they had increased levels of RET. They went on to show that reducing the levels of RET actually makes the breast cancer cells more sensitive to tamoxifen and more likely to die.

Speaking from the Breakthrough Breast Cancer Research Centre at the ICR, in London, where she leads the Molecular Cell Biology Team Professor Isacke said: “We are very excited by these findings. Our challenge now is to work out how RET activates the oestrogen receptor so that we can develop new treatments for tamoxifen-resistant breast cancers"

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