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Driving changes in womb cancer detection

New approaches to womb cancer detection are driving changes for patients through improved and earlier detection and subsequent treatment methods. This pioneering research is being led by Professor Emma Crosbie, who describes her practice-changing research and outlines why she thinks a prevention and early detection approach is needed in cancer research.

As the early detection lead for the National Institute of Health Research (NIHR) Manchester Biomedical Research Centre (BRC), my aim is to detect cancers at their earliest treatable stage when it's a lot more likely that treatment will be curative.

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

Image: Professor Emma Crosbie

Professor Emma Crosbie

Emma Crosbie is Professor of Gynaecological Oncology at The University of Manchester and Manchester University NHS Foundation Trust. She is also the lead for the cancer prevention and early detection research theme at the NIHR Manchester Biomedical Research Centre.

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Womb cancer and 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.

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 the syndrome and that those who test positive can be offered bowel-cancer screening to detect and remove pre-cancerous polyps. This has been shown to save lives.

“In future, more people could 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. ”

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) that 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 with a blood test. This blood test is expensive and takes a long time to complete, so it is important to rule out women who are unlikely to have Lynch syndrome from those who are at risk. This can be done by performing simple tests on their tumours, which includes screening for mismatch repair deficiency by immunohistochemistry and genetic testing for microsatellite instability, both of which are hallmarks of the syndrome.

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 blood testing for Lynch syndrome. 

In future, more people could 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, because womb cancer usually presents 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.

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Raising awareness through research

The link between Lynch syndrome and womb cancer presents a real opportunity to improve outcomes for patients – but it's an opportunity that at the moment is being missed because we just don't do it consistently.

However, we have registered our research findings with NICE and they have agreed to set up a diagnostic advisory group, so we're actually making good progress. We should know the final outcome by the end of 2020 at the latest, and then hopefully the guidance will be updated to ensure that everyone diagnosed with womb cancer is automatically screened for Lynch syndrome. This is another great example of how research undertaken at Manchester is changing national policy.

Despite womb cancer being the most common gynaecological cancer affecting women in the UK, there is low public awareness and less research funding compared with other types of cancer.

One of my key ambitions is to champion womb cancer awareness. 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.

“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 work has demonstrated that if very obese women lose weight then cancer precursors are more likely to 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's 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.

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.

Learn more about research into cancer prevention and early detection at the NIHR Manchester Biomedical Research Centre.