Study shows PROMISE in being able to predict ovarian cancer risk in every woman.

Today a paper was published from the PROMISE programme called 'Population study of ovarian cancer risk prediction for targeted screening and prevention', Karen Hobbs blogs about the move forward for a more personalised population wide ovarian cancer prevention programme.

As most of you reading this probably know, The Eve Appeal funds world-class research into the early detection, risk prediction and prevention of gynaecological cancers. One of the projects that we have proudly been involved in funding is the international, PROMISE programme, which stands for Predicting Risk of Ovarian Malignancies, Improved Screening and Early detection. PROMISE, led by Prof Ian Jacobs, took place over seven years, ending in 2019.

We’re really excited at Team Eve, as the first paper from this PROMISE has been released today, a pilot trial allowing all women involved to get a personalised estimate of their risk of ovarian cancer. This will allow them to find out if they are at an increased risk and then be able to make decisions allowing them to minimise this risk, either by having preventative surgery, or to have regular screening. The study was led by Prof Ranjit Manchanda from Barts Cancer Institute and Wolfson Institute of Preventive Medicine, Queen Mary University of London, who believes that with the advances happening in genomic medicine, we have an opportunity to deliver a new population-based predictive, preventive and personalised strategy for cancer prevention: “Our findings support broadening genetic testing for ovarian (and breast) cancer genes across the entire population, beyond just the current criteria-based approach to better identify women at risk. This could prevent thousands more cancers than any current strategy, saving many lives.”

Why We Need to Prevent Ovarian Cancer

Around 70% of ovarian cancer cases are currently being diagnosed at stage 3 or 4, meaning the treatment is more brutal and the outlook is poorer than a stage 1 or 2 ovarian cancer, when the patient will have a much higher chance of survival. Why is ovarian cancer too often diagnosed too late? The signs are much harder to spot than with the other gynaecological cancers and they are often only noticeable when the disease has already spread. However, in high risk women this is a ‘preventable’ cancer. Ovarian cancer can be prevented through an operation to remove both tubes and ovaries. Prof Ranjit Manchanda is also working on a study to allow for a two-step prevention procedure, first removing the Fallopian Tubes followed later down the line with surgery to remove the ovaries, this study is called PROTECTOR.

What Makes Women at Risk of Ovarian Cancer?

There are a number of other risk factors that cause ovarian cancer, as well as our genetics. The non-genetic factors include pill use, age, number of children, etc. The most well-known genetic link to ovarian cancer is the BRCA genes. Every one of us has the BRCA gene, but a BRCA1 or BRCA2 gene alteration, is a genetic condition that puts the women affected at a 17-44% (depending on the BRCA variation) lifetime risk of ovarian cancer, compared to an average lifetime risk of 2% for the general population. Ovarian cancer affects around 7,300 people every year in the UK, and we know that 15-20% of these cases are caused by a BRCA gene alteration. Around 1 in 200 to 1 in 300 of the general population will be affected by BRCA, with that number rising to 1 in 40 people who are of Ashkenazi Jewish heritage.

Prof Manchanda has previously led research offering BRCA testing to everyone in the Jewish community. Now, the paper today goes one step further and shows the acceptability and potential benefits of assessing not just people of Jewish heritage’s risk of ovarian cancer, but of those in the wider general population.

What The Study Found

103 participants had their genetic, epidemiology and hormonal data collected, assessed through a personalised ovarian cancer risk tool. Through this unique tool, followed by risk management, one member of the study actually discovered that she was at high risk of developing ovarian cancer, and was able to take the necessary preventative measures. None of the 103 participants would have routinely been offered genetic testing on the NHS (as they did not fulfil current clinical testing criteria).

The study looked at the uptake of risk assessment, the use of a customised decision tool, the women’s satisfaction with the process as well as impact on psychological well-being and quality of life. 98% of the women were satisfied with their decision and 92% were satisfied with the decision tool.

98% of participants said that finding out their ovarian cancer ‘risk status’ made them feel less worried. In cancer research and medicine, the focus is on the disease itself and how we can either prevent or treat a particular type of cancer. The mental health aspect of cancer diagnosis or the anxiety caused by knowing that you’re at a significantly increased risk of cancer, is a big issue for many and not something that should be glossed over.

BRCA Testing in the NHS Today

The current criteria for BRCA testing in the NHS means that someone either has to be diagnosed with a breast or ovarian cancer themselves to be offered testing, or someone who is pre-diagnosis needs to have two of more first degree relatives (parent, sibling, child) on the same side of the family who have had a breast and/or ovarian cancer diagnosis. Currently most people who carry a BRCA alteration do not get identified using this current criteria-based approach. Prof Manchanda says: “Why do we need to wait for women to get cancer to identify others in whom we can prevent cancer? A population testing approach can change this. With the costs of testing falling and our knowledge increasing, it is now the right time to make this change.”

This paper from the PROMISE project shows that assessing someone’s risk of ovarian cancer, regardless of their family history, is possible and allows us to take control of our future. Prof Ian Jacobs says: “If women identified as high-risk act on the information that they’re given they can take preventative action to reduce their risk or undertake regular screening. Then the impact that this study could have on healthcare in the future for these cancers is promising and an exciting step forward in prevention”. The findings also suggest population-based personalised ovarian cancer risk estimation has high satisfaction, reduces cancer worry or risk-perception, and does not negatively impact psychological-wellbeing or quality-of-life.

Through this small but profound feasibility study, one person’s life has already been potentially saved. With population-wide testing, people can protect themselves, and parents can protect their children, before their own lives are put at risk.

This study was supported by researchers at University College London, University of Cambridge, Kings College London, Birmingham Women’s NHS Foundation Trust, Manchester Centre for Genomic Medicine, London School of Hygiene and Tropical Medicine, Southampton University Hospital and University of New South Wales.

You can read it in full on MDPI