Tuesday, June 28, 2016

Twice as many women with 'Angelina Jolie gene' should have OVARIES removed to reduce the risk of inherited cancer

Thousands more women should have their ovaries removed in their 40s to reduce the risk of cancer, experts say. 

Women are often advised to have their ovaries and fallopian tubes removed if they have a mutated BRCA gene - famously carried by Angelina Jolie - which significantly increases the risk of ovarian and breast cancer.

At present, women are offered an operation if they have a 10 per cent lifetime risk of getting ovarian cancer, which doctors calculate by testing their genes and examining their family history.

But experts now want to lower the threshold to 4 per cent, which would enable many more women to have the surgery.

A research team at St Mary's University of London and University College London calculates this would save many more lives - significantly reducing the risk of ovarian cancer, as well as bringing down numbers of breast cancer.

Ovarian cancer is the fifth most common cancer among British women, with more than 7,000 diagnosed each year, and 4,300 women dying as a result.

Early diagnosis is key to survival, but three-quarters of women are diagnosed once the cancer has already spread, making it much harder to treat.

Removing ovaries before there is any sign of the cancer massively reduces the risk - but most doctors are reluctant to advise such a drastic step unless there is a significant risk that cancer will develop.

Nearly 4,000 women undergo surgery to extract their ovaries in Britain each year, many of them to lower their chance of developing ovarian cancer later in life. 

The procedure triggers early menopause, usually requiring a women to take hormone replacement therapy (HRT) pills until the normal menopause age in the early 50s.

Doctors often advise that a woman undergoes the procedure if they have a mutated BRCA1 gene, which raises the risk of ovarian cancer from 1.3 per cent to 39 per cent.

But recent advances in genetic science have unveiled a number of other genes which also increase ovarian cancer risk - including mutations of the BCRA2, RAD51C, RAD51D, and BRIP1 genes.

Interest in genetic risk soared after Miss Jolie, 41, famously chose to have her breasts, ovaries and fallopian tubes removed to reduce her cancer risk, after her mother died of ovarian cancer aged just 56.

Referrals for genetic testing doubled in Britain in the two months after Miss Jolie announced she underwent the first of her procedures in 2013.

But experts have said that the threshold for the procedure is too high - and more of those who test positive for the genes should be offered the operation. 

The researchers, whose work is published in the Journal of Medical Genetics, calculated the effectiveness of pre-emptive surgery for women aged at least 40 who had not yet gone through the menopause.

Using mathematical models, they calculated the benefits of the operation for different lifetime risk thresholds —from 2 per cent to 10 per cent — to work out the likelihood of developing ovarian cancer, breast cancer, and death from heart disease.
They calculated that pre-emptive surgery at a lifetime risk level of 4 per cent or greater would reduce risk and remain cost-effective, adding up to 43 extra days of life expectancy.

The team wrote: 'The shifting landscape resulting f4rom new genetic discoveries, better risk estimation and rapidly changing genetic testing technology has important implications and offers opportunities for cancer risk management and prevention.

'Our results are of major significance for clinical practice and risk management in view of declining genetic testing costs and the improvements in estimating an individual's ovarian cancer risk.

'With routine clinical testing for certain moderate penetrance genes around the corner and lack of an effective ovarian cancer screening programme, these findings are timely as they provide evidence supporting a surgical prevention strategy.'
They added: 'Such an approach can contribute to decreasing the number of ovarian cases and disease burden within the population.

'This is a key measure needed for moving towards a predictive, preventive, personalised and participatory medicine.'
Katherine Taylor, chief executive at the charity Ovarian Cancer Action, said: 'We welcome this study as it helps raise the profile of cancer prevention strategies for women at risk of ovarian cancer.

'It also demonstrates that it's vital for women to have informed discussions with their clinicians about their personal risk, options for preventing ovarian cancer - particularly for those who have an inherited predisposition - and the role of HRT after any surgery.

'The key is to know your options and risk so you can choose the path that's right for you.'
Annwen Jones, chief executive of Target Ovarian Cancer, said: 'These are positive results and any potential in reducing the number of people dying from ovarian cancer is to be welcomed.

'To gain these benefits, it will be important to see how the algorithms calculating the risk of ovarian cancer could be implemented in clinical practice.

'It is essential that any woman considering her risks has access to appropriate advice and support to understand the risks and benefits of preventative surgery.'

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