New cancer risk test based on routine cervical screening sample can identify breast and ovarian cancer and may help in future cancer risk prediction

Our research, published today in Nature Communications, provides new tools, the Women’s cancer risk identification for breast cancer and ovarian cancer (WID-BC and WID-OC) tests, which can detect these two cancers using only routine cervical screening samples. Importantly, the tests do not detect actual cancer but rather indicate genetic, lifestyle and environment risk factors associated with them and may be able to predict future risk. In this blog, researcher Dr Chiara Herzog goes into detail of how the test works and who it could benefit. Chiara Herzog, Ph.D. (twitter: chiara_herzog)

Breast and ovarian cancer are two diseases with a considerable burden on both individual patient wellbeing and society. Breast cancer is the most common cancer in women, accounting for more than half a million deaths worldwide in 2020. Although screening tools do exist, around a quarter of breast cancer cases in the UK are thought to be preventable, highlighting the need for more thorough screening and prevention approaches.

While ovarian cancer is not as common as breast cancer, it is often only detected in the late stages when treatments are less effective.

Prevention methods for both breast and ovarian cancer are available: removing the breasts or ovaries can reduce the risk for developing these cancers down to essentially 0%, but it’s often not clear whether this rather drastic step is required.

Breast cancer

Breast cancer affects approximately 55,000 women each year in the UK. Screening is currently available for women and people assigned female at birth with breasts aged 50 to 70 to help find breast cancer in the early stages but generally requires specialist equipment such as X-ray or MRI machines and may trigger other tests or surgeries when perhaps not required. There is currently no preventative screening method in the UK for breast cancer.

Ovarian cancer is often detected (too) late

Ovarian cancer is a devastating disease affecting hundreds of thousands of women and people with ovaries worldwide each year and is the leading cause of gynaecological cancer-related deaths in the UK. Unfortunately, when ovarian cancer first develops, it may not cause any noticeable symptoms and even once symptoms occur, these can be unspecific: bloating, back pain, fatigue, feeling full quickly when eating, and changes in bowel habits. While increasing symptom awareness and improvements in treatments will help to reduce the mortality of ovarian cancer, earlier detection or even prevention are likely the options that will have the biggest impact for patient survival and quality of life. This is particularly important for those with an increased risk, such as individuals with an alteration in the BRCA gene.

Preventive strategies do exist, but how do we know who needs them?

At least one method to prevent breast and ovarian cancer does already exist: removal of the breast and/or ovaries. This contrasts with other cancer types, such as lung or bowel cancer, where removal of the organ is not a viable option. However, it is a big decision that can affect your body image, fertility and long-term health. In order to both improve quality of life and reduce cancer risk, we need to better predict individual risk and/or early detect these two cancers to enable women and people assigned female at birth to make informed decisions about their bodies.

Capturing and monitoring cancer risk using the epigenome

Capturing individual disease risk is not an easy task as cancer development is complex: we already know that genetic factors contribute (e.g. BRCA gene alterations), but genetics is not solely to blame. Many other factors, including our lifestyles – whether we smoke, pollution, how often we exercise, and what we eat – contribute to various cancers. For breast and ovarian cancer, hormones also play a large role. To measure someone’s risk, we have to look at all of these different factors and assess how they will contribute to cancer in that individual. Luckily, there is a molecular signature that enables just that: the epigenome.

The epigenome – for now we focus on a certain type of the epigenome called “DNA methylation”– is an extra layer of information on our DNA. Our DNA contains all of the genes we inherit from both our parents, and every cell in the body contains all of this DNA. It is DNA methylation that tells the cell which bits of DNA to read, by leaving little marks on top of some of the DNA – so it knows which cell it is and what it is supposed to do. Our lifestyle and environment (such as smoking, pollution, diet etc) can alter these marks and change how the cell behaves. Our recent findings suggest that we can read these marks to detect cancer and hopefully predict the risk someone has of developing cancer in the future.

Routine cervical screening samples could be used to diagnose breast and ovarian cancer

Our new research in Prof. Martin Widschwendter’s team, a gynaecological oncology surgeon and epigenome expert, suggests that we can use the WID-BC and WID-OC tests on samples from cervical screening to detect breast and ovarian cancer from DNA methylation, and hopefully give an indication of future cancer risk.

Our team looked  at DNA methylation in cervical samples of current breast or ovarian cancer patients and healthy women, and we found two signatures that faithfully identified women with either breast or ovarian cancer. Importantly, we found that these epigenetic “cancer” signatures are not dependent on actual tumour material in the cervical sample, but instead indicate changes with DNA methylation associated with tumour development and may therefore also enable risk prediction rather than detecting cancers which are already present. This is particularly exciting as it is a totally new method of cancer screening and may be used to help prevent cancers from developing. Other screening methods in development look for early signs of cancer and will be used for early diagnosis of disease.

What does this mean for you and when could it be seen in the clinic?

We believe that these two tests – WID-BC and WID-OC- could help to drastically reduce ovarian and breast cancer diagnoses at late stages and improve women’s quality of life. The tests themselves are based on samples taken from cervical screening, so no additional screening tests would be needed. However, as with any new test, they will need trialling on a large number of the population over the next years before being available widely on the NHS. Our next research will also discover whether the tests are best suited for screening all women and people with a cervix, or only in those with a known increased risk of these cancers (eg. people with a BRCA alteration or family history).

We hope that the WID-BC and WID-OC tests will enable people to take control over their life, empower them to make informed decisions on whether preventative surgery is the right decision for them and save lives.

You can read the papers published today in Nature Communications:

Ovarian cancer

Breast cancer