Changing lives and national policy

Professor Emma Crosbie discusses research into the link between Lynch syndrome and womb cancer, and how this has changed NICE guidance on testing for the syndrome.

My main research interest is endometrial (or womb) cancer, which is the fourth most common cancer affecting women in the UK, yet it is poorly studied and understood.

At the moment, women with suspected womb cancer have to undergo a series of sequential, painful, invasive tests. But for every 100 women who get tested, maybe only five of them will actually have cancer - so that's a lot of women exposed to unnecessary and expensive tests.

My idea is to develop new ways of triaging women into those who genuinely are at high risk of womb cancer, and those who are not, so as to quickly reassure the vast majority of healthy women while concentrating clinical care and resources on those with cancer.

Lynch syndrome

Almost 3% of womb cancers are linked to an inherited cancer pre-disposition condition called Lynch syndrome, which affects about 1 in 300 people globally. A similar proportion of bowel cancers are caused by Lynch syndrome, which has led to guidance from the National Institute for Health and Care Excellence (NICE) that anyone diagnosed with bowel cancer should be tested for the condition.

This is because knowing that a person has Lynch syndrome can help determine which cancer treatments are likely to be successful. It also means that patients' family members can be screened for Lynch syndrome, and those who test positive can be offered bowel cancer screening, to detect and remove pre-cancerous polyps in the bowel. This has been shown to save lives from bowel cancer.

While the link between Lynch syndrome and bowel cancer is well established, the link with womb cancers is less well studied. So, in partnership with Professor Gareth Evans, I led the first prospective UK study to determine the prevalence of Lynch syndrome in 500 women newly diagnosed with womb cancer.

Lynch syndrome is caused by a fault in one of the four so-called mismatch repair (MMR) genes. These genes allow our cells to repair mistakes to our genetic code (our DNA), which occur randomly when our cells divide and produce new cells.

The gene fault responsible for Lynch syndrome can be found by testing a person's DNA via a blood test. This blood test is very expensive and takes a long time to complete, so it is important to sift out women who are very unlikely to have Lynch syndrome from those who are at risk by performing simple tests on their tumours first.

This includes testing tumours for mismatch repair deficiency by immunohistochemistry, and genetic testing for microsatellite instability, both of which are hallmarks of Lynch. Patients scoring positive on either of these measures may then be tested for MLH1 hypermethylation. Together, these tumour tests reduce the number of women identified as being 'at risk' by around 90%, leaving just 50 or so of the original 500 women to undergo the more expensive and time-consuming germline testing for Lynch syndrome.

The initial findings of my research indicate that Lynch syndrome is found in around 3% of women with womb cancer - exactly the same proportion as in bowel cancer. My research also showed how womb cancer should be screened for Lynch syndrome, that women want to be tested to protect their family members, and that Lynch syndrome testing is cost effective for the NHS.

As a result, NICE has now extended its guidance on Lynch syndrome testing to include women diagnosed with womb cancer, as well as bowel cancer. This means that more people will be enrolled in cancer prevention and screening programmes, as clinicians will be in a better position to encourage the relatives of patients with Lynch syndrome to be tested for the disease.

In addition - and crucially - because womb cancer usually comes first, it is likely be the first indication of a patient having Lynch syndrome and therefore being at risk of developing bowel cancer later in life. The link between Lynch syndrome and womb cancer presents a real opportunity to improve outcomes for patients. We are delighted that NICE has developed new guidance that recommends everyone diagnosed with womb cancer is automatically screened for Lynch syndrome. It is another great example of how research undertaken in Manchester is changing national policy.

Despite being the most common gynaecological cancer affecting women in the UK, there is less overall public awareness and in turn less research funding, when compared with other types of cancer. So, one of my key ambitions is to champion womb cancer. There are so many opportunities to make things better by raising public awareness about the disease, encouraging women with symptoms to see their doctor straight away and speeding up the pathway to diagnosis.

Obesity and womb cancer

I've also been researching the link between obesity and womb cancer - specifically the impact of weight loss on early pre-cancerous changes in the lining of the womb. This has demonstrated that if very obese women lose weight, then cancer precursors can simply disappear. We're already getting extremely good outcomes for obese patients who lose weight and receive hormone therapy to treat their womb cancer, rather than the standard hysterectomy. And, of course, this has the huge advantage that it is possible for these women to achieve pregnancy once the treatment is completed.

In Manchester, we have the UK's only clinic for this type of management of womb cancer. To date, we've treated 110 women from all over the country, as few clinics are routinely offering this 'conservative' approach to treatment - most can only offer a hysterectomy. We're fairly unique in being able to bring together gynaecologists, dieticians, bariatric surgeons, anaesthetists and fertility experts in a multidisciplinary approach to deliver the best possible care for patients.

A centre of excellence for Prevention and Early Detection

The city already has an international reputation for cancer research excellence. It receives a phenomenal amount of funding from Cancer Research UK (CRUK) and also the NIHR via the Manchester BRC. In fact, Manchester is the only BRC in the country that has a Cancer Prevention and Early Detection (PED) theme, and the city is home to one of the only three CRUK Early Detection centres in the entire country.

Manchester is also fairly unique in being able to bring together brilliant discovery scientists and clinical academics who can then work with patients to test new discoveries – and, for my research, that's a perfect marriage between innovation and testing new diagnostics and treatments in the right people.

As lead for the PED theme at the Manchester BRC, my personal ambition is to see Manchester develop as an internationally recognised centre of excellence for cancer PED. We've got all of the elements in place, but to take things to the next level we need to have new biomarkers to test sequentially in high risk groups and then more general populations.

Manchester: a PED centre of excellence

The city already has an international reputation for cancer research excellence. It receives a phenomenal amount of funding from Cancer Research UK (CRUK) and also the NIHR via the Manchester BRC. In fact, Manchester is the only BRC in the country that has a cancer prevention and early detection (PED) theme, and the city is home to one of the only three CRUK early-detection centres in the entire country.

Manchester is also fairly unique in being able to bring together brilliant discovery scientists and clinical academics who can then work with patients to test new discoveries. For my research, that's a perfect marriage between innovation and testing new diagnostics and treatments in the right people.

As the lead for the PED theme at the Manchester BRC, my personal ambition is to see Manchester develop as an internationally recognised centre of excellence for cancer PED. We've got all the elements in place, but to take things to the next level we need to have new biomarkers to test sequentially in high-risk groups, and then in more general populations.