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Breast cancer patients given tamoxifen are more than four times more likely to develop a more aggressive tumour than those not prescribed the drug, scientists have warned.
A study of over 1,000 patients found the oestrogen blocking drug reduced the risk of the most common, easy to treat cancer recurring by 60 per cent.
But the chances of a rarer type not sensitive to the female hormone appearing in the opposite breast increased by an alarming 440 per cent.
These are known as ER negative tumours, as opposed to ER positive, and are much more dangerous as there are no drugs that specifically target them.
Dr Christopher Li, of the Fred Hutchinson Cancer Research Centre in Seattle, said: 'This is of concern, given the poorer prognosis of ER-negative tumours, which are also more difficult to treat.'
Tamoxifen has been used to treat breast cancer for more than 20 years and has saved the lives of hundreds of thousands of women worldwide.
But Dr Li, whose findings are published in the journal Cancer Research, said although it has been shown to reduce the risk of dying from the disease it does have risks.
The study confirms preliminary research by the same team published in 2001 which was the first to suggest a link between long-term tamoxifen use and an increased risk of ER-negative second cancers.
Dr Li said: 'The earlier study had a number of limitations. For example, we did not have information on the duration of tamoxifen therapy the women received.
'The current study is larger, is based on much more detailed data, and is the first study specifically designed to determine whether tamoxifen use among breast cancer survivors influences their risk of different types of second breast cancers.'
The latest research assessed history of tamoxifen use among 1,103 breast cancer survivors who were initially diagnosed with ER positive breast cancer between the ages of 40 and 79. Of these, 369 of the women went on to develop a second breast cancer.
Nearly all of the women in the study who took hormonal therapy used tamoxifen specifically. Detailed information about tamoxifen use was ascertained from telephone interviews and medical record reviews.
Oestrogen encourages the growth of some breast cancer cells. Tamoxifen interferes with this action by attaching itself to the molecule, or receptor, on a cancer cell surface that is also used by the hormone.
This, in effect, blocks the oestrogen effect on the cancer cells. Cancer cells without an oestrogen receptor are not affected by tamoxifen.
Dr Li said while the study confirmed a strong association between long-term tamoxifen therapy and an increased risk of ER-negative second cancer, it does not suggest that breast cancer survivors should stop taking hormone therapy to prevent a second cancer.
He added: 'It is clear that oestrogen-blocking drugs like tamoxifen have important clinical benefits and have led to major improvements in breast cancer survival rates.
'However, these therapies have risks, and an increased risk of ER negative second cancer may be one of them.
'Still, the benefits of this therapy are well established and doctors should continue to recommend hormonal therapy for breast cancer patients who can benefit from it.'
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