Many more people who could carry genes putting them at increased risk of ovarian cancer may be offered genetic testing on the NHS, subject to responses to a public consultation on a new draft guideline from the National Institute for Health and Care Excellence (NICE).
As well as increasing the availability of genetic testing, the guideline aims to promote greater awareness among those with elevated risk to take preventive measures, such as surgery.
NICE pointed out that currently only around 3% of people of the estimated 340,000 to 440,000 women in the UK with a pathogenic variant know that they have a high-risk gene. "Hundreds of thousands of people could benefit" from increased testing, NICE said.
Up to One in Five With Cancer Carry Pathogenic Variants
The guideline identified nine pathogenic variants associated with increased ovarian cancer risk – BRCA1, BRCA2, RAD51C, RAD51D, BRIP1, PALB2, MLH1, MSH2, and MSH6. Among those with high-grade epithelial ovarian cancer, 15% to 20% carry pathogenic variants.
Commissioners and service providers should ensure appropriate pathways with clear criteria for referral to genetics services for testing and counselling, NICE stated. This should include people with blood relatives affected by breast or ovarian cancer, and patients with:
- Invasive epithelial ovarian cancer
- Ovarian Sertoli–Leydig cell tumour
- Small cell carcinoma of the ovary hypercalcaemic type
- Ovarian sex cord tumour with annular tubules
- Embryonal rhabdomyosarcoma of the ovary
- Ovarian gynandroblastoma.
The likelihood of pathogenic variants should be assessed using a mathematic model with demonstrated accuracy, such as the Manchester scoring system, CanRisk (BOADICEA), BRCAPRO, or criteria based on family history. Genetics services should also arrange cascade testing of relatives, if appropriate.
Some Ethnicities at Higher Risk
The current threshold for testing is a 10% probability of carrying a high-risk gene. The new guideline recommends that this drops to as low as 2% for younger women, aged 30 to 49.
NICE noted that people from Ashkenazi and Sephardic Jewish backgrounds are more likely to carry BRCA1 and BRCA2 genes, linked with both breast and ovarian cancer. Around 280,000 people from these backgrounds could become eligible for testing, alongside around 1000 people of Greenlander heritage who are also at higher risk.
The guideline itself would "help to build a better picture of how many people have the high-risk genes", as more people come forward for testing, according to NICE.
If testing reveals a pathogenic variant, the most effective intervention is bilateral salpingo-oophorectomy, sometimes with hysterectomy, to reduce the risk of endometrial cancer as well. Surgery should be offered only to those who had completed their family or could not conceive naturally, and who had a total lifetime risk of ovarian cancer of 4% or over, if premenopausal, or 5% or over if postmenopausal.
Professor Jonathan Benger, NICE's chief medical officer and interim director of the centre for guidelines, said: "We aim to raise awareness of people’s risk, helping them get the best supportive care and reducing the devastating impact ovarian cancer can have on people and their families.
"While there will be an initial upfront cost associated with setting up multidisciplinary teams and increasing genetic testing, the risk-reducing surgery we recommend could save lives while also saving the NHS money and resources in the long run."
Awareness of Ovarian Cancer "Too Low"
Asked to comment by Medscape News UK, Rachel Downing, head of policy and campaigns for Target Ovarian Cancer, said: "Identifying those at risk for developing ovarian cancer is an important step in combating this devastating disease, which is the sixth most common cause of death in women in the UK.
"At Target Ovarian Cancer, we know awareness of ovarian cancer is too low, and so it is not surprising that only 3% know they have a high-risk gene. More needs to be done to increase awareness generally, and the draft guideline released today is a promising step forward and will help to improve outcomes."
Also commenting to Medscape News UK, Athena Lamnisos, CEO of gynaecological cancer research charity the Eve Appeal, welcomed the "comprehensive" guideline, noting that understanding of genetic and personal risks had lately "accelerated" and that referral for testing should embrace "as wide a group as possible".
It was "crucial that stakeholders all take note and respond", she said, "so that the guideline can be optimised" and care improved nationally to reduce postcode lottery issues.
"It’s also vital to ensure that the right training and education for healthcare professionals is in place, as this is key to providing patients with the information and support they need to make the best informed decision for them." Testing may now be simple, she said, but the complexity of making risk-reducing decisions "shouldn’t be underestimated".
The public consultation runs until 27 October.