A scientist analysing DNA in the lab

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Every year in the UK more than 7,000 women are diagnosed with ovarian cancer.

But some of these women have a much higher risk of developing the disease than the general population.

That’s because they have inherited faults in the BRCA1 and BRCA2 genes.

These faults are most commonly linked to an increased risk of breast cancer. But research estimates suggest that between 5 and 15% of women diagnosed with ovarian cancer have tumours harbouring mistakes in these vital genes.

Knowing whether or not an ovarian cancer carries these faults could play a crucial role in deciding which treatment a patient should receive.

And recent research, led by Professor Nazeen Rahman from The Institute of Cancer Research, London, adds more evidence to support the case that BRCA1 and BRCA2 genetic testing should be offered to all women diagnosed with ovarian cancer.

But even with the weight of evidence in its favour, it seems that genetic testing isn’t happening for everyone.

So why is this?

The importance of BRCA1 and BRCA2

These two genes, made famous by high-profile carriers such as Angelina Jolie, are an important part of the molecular machinery that repairs DNA when it gets damaged.

Research into how the genes work – and how they go wrong in cancer – led to the development of a new type of treatment that exploits a vulnerability in cancer cells’ ability to keep their DNA in working order: PARP inhibitors.

And in 2015, we reported the good news that the National Institute for Health and Care Excellence (NICE) recommended one particular PARP inhibitor, called olaparib, as a treatment for women with ovarian cancer caused by mistakes in the BRCA1 or BRCA2 genes.

Crucially, this means that the drug won’t work in women whose tumours have working BRCA1 and 2. And it could lead to unnecessary side effects.

So doctors need some way of telling which women should be given the treatment.

The benefits of a genetic test

The immediate benefit of offering all women with ovarian cancer a genetic test is to tailor treatment for each patient, says Dr James Brenton, a Cancer Research UK funded ovarian cancer specialist in Cambridge.

“Since olaparib was approved, there is a very strong argument for testing all women with ovarian cancer, because between 5 and 15% of these women could be given a more effective treatment option based on the results of this test,” he says.

Improving treatment for patients right now is reason enough to make sure that all women are offered a genetic test, but the advantages don’t end there.

Because mistakes in BRCA1 and 2 can be inherited, finding these faults in a test has potential implications for their close relatives too because they might also be carrying the same genetic faults. And knowing this information can help people make decisions to reduce their risk of certain cancers.

“Women with faulty BRCA1 and 2 genes have a higher chance of developing breast and ovarian cancers,” says Brenton. And knowing this means they can “choose options that reduce this risk, including surgery to remove all breast, fallopian tube and ovarian tissues, or hormone therapies that help stop these cancers developing,” he adds.

According to Rahman’s team, identifying the relatives of women with ovarian cancer who carry faulty BRCA 1 and 2 genes could also prevent cancers in the future. They predict that if all women with ovarian cancer in the UK were offered a genetic test and chose to have treatment to reduce their risk, this could result in 283 fewer cases of breast and ovarian cancer over the next 50 years, and 77 fewer deaths from these diseases.

But even if women choose not to have surgery or take hormone therapy to reduce the risk of cancer, knowing they are at higher risk means they can be more regularly monitored for early signs of cancer, increasing the chances of successful treatment.

And it’s not only women affected either.

Men with faulty BRCA1 and 2 genes are at higher risk of developing an aggressive form of prostate cancer. There are on-going clinical studies to find out if screening could spot early signs of disease in this high risk group and looking at the potential benefits of PARP inhibitors as a treatment. But unlike women with these genetic faults, there aren’t yet clear, risk-reducing treatment options for these men.

When and where to test?

In the past, because there were no better therapies to offer women with ovarian cancer caused by faulty BRCA1 and 2 genes, testing was only offered in genetics clinics to women with a strong family history of the disease.

If the test is positive for inherited faults in BRCA1 and 2 genes, then women can be referred to a genetics clinic to discuss the wider implications for their family

– Dr Marc Tischkowitz, University of Cambridge

Genetic Counsellors have an important role to play, because the results of genetic tests can be complex and nuanced. Furthermore, measures that people without cancer can take to reduce their risk of getting the disease can have a big emotional and physical impact – so it’s important that people have all they information and support they need to make these decisions.

But the development of more effective treatment for those carrying these faulty genes has changed the situation; now doctors need to know this information to tailor therapy.

The question then is, would offering routine testing to all ovarian cancer patients without the support of a genetics clinic cause distress or unnecessary worry? Not according to Rahman’s research, or a larger earlier study carried out by Brenton and Dr Marc Tischkowitz from the Department of Medical Genetics in Cambridge.

While Rahman’s study focused on a single hospital, the Cambridge team looked at genetic testing across a whole region. But crucially, both studies showed women with ovarian cancer were happy to have genetic testing without going via a genetics clinic. In fact, many women actually preferred this option.

Rahman’s findings also show that including testing in a routine cancer appointment meant the results were available in a quarter of the time it would take going through the normal route.

And according to Tischkowitz, this wouldn’t stop patients then being referred for specialist help available at a genetics clinic.

“If the test is positive for inherited faults in BRCA1 and 2 genes, then women can be referred to a genetics clinic to discuss the wider implications for their family,” he says.

“But it’s cheaper and quicker to do the testing through a routine cancer appointment rather than sending women to a genetics clinic, and it reduces the risk of delaying the start of treatment.”

Is it too expensive for the NHS?

In the past, genetic testing was a lengthy, expensive process. But thanks to improved technology, this has changed.

“Carrying out a BRCA1 and 2 gene test would take months and cost thousands of pounds back in the early 2000s, but nowadays the cost of the test has fallen to a few hundred pounds and can be done in a matter of weeks,” says Tischkowitz.

“It’s also clear that the chance of finding a mistake drops dramatically in women diagnosed at an older age – only around 1% of women diagnosed over 70 will have faults in BRCA1 or BRCA2 – so we should look at the advantages of only testing younger women,” he adds.

There are also savings to be made for the NHS by streamlining cancer care and reducing unnecessary appointments at genetics clinics. According to Rahman’s team, this could be as much as a £2.6 million a year saving by only referring women who definitely have faulty BRCA1 or 2 genes.

But genetics clinics still have a crucial role to play. More routine genetic testing in the future means the Government needs to make sure there are enough Genetic Counsellors to cope with demand. It’s an issue that genetics expert Dr Anna Middleton, also based in Cambridge, is passionate about.

“At the moment there are only around 300 Genetics counsellors in the UK,” she says. “We urgently need more. The NHS is training more Genetic Counsellors to address this gap in the workforce, but it doesn’t help with the current shortfall. It needs to stay high on the priority list.”

Patchy access

The advantages of BRCA1 and 2 genetic tests for women diagnosed with ovarian cancer are clear-cut – better treatments for patients right now, fewer cases of cancer and reduced cancer deaths in future, and even savings for the NHS.

The inclusion of BRCA1 and 2 genetic testing as part of routine ovarian cancer care is already standard at some hospitals around the country, including The Royal Marsden in London, Cambridge University Hospitals for East Anglia, Manchester, Edinburgh and Glasgow.

Targeted medicines offer real promise to patients, but only if patients get the tests required to identify whether they would be suitable for them

– Emlyn Samuel, Cancer Research UK

And both NICE and England’s cancer strategy have recommended that women with ovarian cancer should have access to BRCA testing.

So why isn’t it happening in every hospital?

“It’s a big task changing the guidelines that cancer specialists follow to treat cancer patients,” Brenton says. “This has to involve the local commissioning groups and it’s not simple to do.”

But it needs to happen.

Emlyn Samuel, Cancer Research UK’s senior policy manager, says that access to the right diagnostic tests at the right time is essential if patients are to get the best treatments.

“Targeted medicines offer real promise to patients, but only if patients get the tests required to identify whether they would be suitable for them. And as shown here, providing these tests could have even wider benefits,” he says.

“To make sure patients don’t miss out on these benefits it’s essential that the NHS acts on the recommendations in the new cancer strategy, which calls for all women with ovarian cancer to be offered testing for BRCA1 and 2 at the point of diagnosis.”

With many more targeted drugs like olapraib in the research pipeline, we’re moving steadily closer to an era of what is called precision medicine, where doctors select the most effective treatments for patients based on the genetic and molecular faults underpinning their individual disease.

But the only way we’ll achieve that aspiration is if the NHS can also offer the right tests to all patients who need them. When they need them.


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