Feature Genetic Testing

Routine testing for women with ovarian cancer

BMJ 2014; 348 doi: http://dx.doi.org/10.1136/bmj.g1200 (Published 26 February 2014) Cite this as: BMJ 2014;348:g1200
  1. Sophie Arie, freelance journalist
  1. 1 London, UK
  1. sophiearie{at}fmail.co.uk

Until now, genetic testing has been offered only to women with a strong family history of ovarian cancer. But as testing gets cheaper and faster, it may soon be possible to test all patients. Sophie Arie looks at the potential benefits and concerns

Genetic testing may soon be offered routinely to all women with ovarian cancer as it could improve their chances of survival and help prevent the disease in relatives.

Until now, doctors have relied on a patient’s knowledge of her family’s medical history to work out if she might be carrying the gene mutations BRCA1 and BRCA2, which increases the risk of developing ovarian and breast cancer.1 But this system misses women who do not have a strong family history or are unaware of their family medical history. Around 7000 new cases of ovarian cancer are diagnosed in the UK every year,2 and 15% of those are in patients who carry BRCA gene mutations.3 Half of those with BRCA gene mutations do not have a family history of the disease.

With gene sequencing technology improving and the cost of genetic testing falling, many medical professionals and patients are convinced that routine testing makes sense.

“This is likely to become de facto, normal, part of what people do,” says Paul Pharoah who studies genetic susceptibility to cancer at the University of Cambridge. If future cancers can be prevented as a result of genetic testing then the value, not just for individuals but for the NHS budget, is obvious.

In Scotland, testing has recently been extended to all women with epithelial ovarian cancer. Charlie Gourley, chair of medical oncology at the Edinburgh Cancer Research Centre, has been offering patients at the University of Edinburgh Western General Hospital genetic testing since November 2012. He estimates that 95% have accepted and says the test can influence decisions about their treatment.

“In a patient with a BRCA2 mutation, we know they will respond to multiple lines of platinum based therapy,” says Gourley. “Although you take each case on merit, you are likely to give them more lines of chemo.”

In Canada and Australia women with non-mucinous epithelial ovarian cancer are now routinely tested for the BRCA1/2 mutations.

But in England and Wales things are moving more slowly.

Implementing new guidance

In April last year the National Institute for Health and Care Excellence (NICE) changed its guidance, lowering the risk threshold above which patients with breast and ovarian cancer are tested for BRCA1 and BRCA2 mutations on the basis that it would benefit patients and be cost effective for the NHS.4 But it stopped short of recommending blanket testing of all patients in part because of concerns this could overload existing services. NICE now recommends that if a patient’s risk of familial breast and ovarian cancer—based mainly on family history—is calculated to be 10% or more she should be offered a genetic test.2 Previously the recommended threshold was 20%.

Ingrid Slade of the Health Economics Research Centre, Oxford University, who is investigating the cost effectiveness of genetic testing in ovarian cancer patients within the Mainstreaming Cancer Genetics Programme, calculates that the new NICE guidance means testing should be made available to 6500 women with ovarian cancer every year who previously would not have qualified.

The price of genetic testing has been falling fast in recent years. At the time it issued its new guidance, NICE estimated the cost of a test at around £700 (€843; $1140). In addition, patients (and subsequently their relatives) need expert counselling to help them decide whether to have the test and how to deal with the results. Currently, genetic counsellors cost around £120 per session, and even if funds were found there are not enough geneticists in the country to cope with a sudden increase in demand for their services.

“There’s a challenge to work out who’s going to pay for these extra tests and how they will be commissioned,” says Slade.

At the Royal Marsden Hospital and Institute of Cancer Research, where the BRCA2 gene was first identified, cancer experts have been experimenting with a similar approach to the Scottish one, where oncologists offer and get consent from patients for genetic testing during their initial consultation after diagnosis. Genetic counsellors become involved only if a patient receives a positive result. A state of the art laboratory has been set up that can test large numbers of samples more efficiently and cheaply than was previously possible.

In a pilot from July to December 2013, 114 women with serous ovarian cancer and at least a 10% chance of having BRCA mutations were offered the test. They all said that they felt sufficiently informed by the oncologist and took up the offer. None reported undue distress in discussing the implications with their relatives.

“The system’s gone very well,” says Professor Nazneen Rahman, who led the pilot. “It is a faster, more flexible, cost effective way of dealing with this. It’s a system we want to roll out.”

This transfer of duties would save money spent by the NHS on each patient tested but also, crucially, time. Currently waiting times for a genetic appointment can be up to 12 weeks. And the genetic test itself can take eight weeks. For some patients this wait is too long.

“The aim is for people to have the test at a time that will impact their treatment,” Rahman said.

Concerns about routine testing

The Marsden’s “oncogenetic” pathway seems to offer a practical and affordable way for cancer services nationwide to test more patients, although the full details of the costs are not yet available. If the cost of genetic testing continues to fall, it could ultimately become feasible for the NHS to offer routine testing this way to all patients.

Ovarian Cancer Action, which invests in research to reduce deaths from ovarian cancer in the UK, has been campaigning for routine testing across the UK since last year year.5

“We would like genetic tests to be made routine for all ovarian cancer patients as this may then improve survival rates and give important information to the families of those affected,” said Gilda Witte, chief executive of the charity.

Patients are increasingly asking their doctors for genetic tests, says Martin Gore, medical director at the Marsden and an oncologist. He says cancer patients have a far greater understanding of genetic testing today than was the case only a few years ago and are asking for the test without wanting much discussion.

“Effectively this is about moving it [genetic testing] from some sort of mythical status into a normal part of what it is to have ovarian cancer and a normal part of what it is for doctors to care for someone with cancer,” said Gore.

The Royal Marsden is also conducting a pilot of the cancer team obtaining consent for BRCA testing in patients with breast cancer, although the potential cost effectiveness is lower because the BRCA1 and BRCA2 genes account for only about 2% of all patients with breast cancer compared with 10-15% of women with ovarian cancer.

While recognising the value of testing more people, some geneticists have reservations about the oncogenetic approach because of the ethical and emotional complexities associated with learning you have a high risk of developing cancer.

Anneke Lucassen, professor of clinical genetics at the University of Southampton, is concerned that there will be less opportunity to discuss potential problems before a decision is made. She said, “If testing is seen as just another one of the battery of tests to be organised then patients might infer it is a necessary part of their care. Whether or not such results will determine different treatments is still at the research stage.”

Lucassen warns also that given the need for hope when a patient receives a difficult diagnosis, the genetic test may be perceived as “some kind of crystal ball” that will give the patient “unrealistic expectations of what a result can deliver.”

And some observe that relatives who had no idea the genes were in their family may find it extremely difficult to come to terms with the news.

“Once the cat’s out of the bag and the family knows they have BRCA1 or 2, it can cause problems for families,” said Pharoah. “It generates huge dilemmas.”

Lucassen warns that routine genetic testing could create problems that counsellors have had little experience of until now. Little is known about how patients with ovarian cancer who are unaware of a family history would react to the discovery that they—and probably their relatives—are carrying the harmful mutations.

Equally, Lucassen notes, relatives who learn that they do not carry the genes may take false reassurance from a negative test result, thinking it means they are clear of any risk (when in fact it just means their risk is lower). The high profile mastectomy of actress Angelina Jolie has “created a big public perception that these genes are it,” says Lucassen. “If you haven’t got them you’re clear.”

At the same time, the group that developed NICE’s 2013 guidelines noted that the lower the threshold for testing the higher the possibility of identifying a “variant of unknown significance” rather than a known causative mutation. This can lead to anxiety and stress for women because of the uncertainties about the cause of their cancer, their future cancer risk, or the risk to other family members.

There are ethical dilemmas for clinicians too, when a patient refuses to inform her relatives of a positive BRCA result because they have fallen out or lost touch. Currently such situations are rare, but as increasing numbers of patients have genetic tests, clinicians may be confronted more often with difficulties over who owns the genetic information they have ordered.


Cite this as: BMJ 2014;348:g1200


  • Competing interests: I have read and understood the BMJ policy on declaration of interests and have no relevant interests to declare.

  • Provenance and peer review: Commissioned; externally peer reviewed.


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