In this post Dr Emma Crosbie, Senior Lecturer & Honorary Consultant Gynaecological Oncologist, tells us about the first ever workshop to develop international standards of care for the management of gynaecological cancers in Lynch syndrome.
What is Lynch syndrome?
Lynch syndrome is an inherited defect in one of the four genes responsible for repairing errors that occur naturally during DNA replication, the so-called mismatch repair genes. Replication errors that are not repaired result in an increased risk of cancer. A person with Lynch syndrome has more than a 50:50 chance of developing cancer during their lifetime, most commonly bowel and womb cancers. Some people with Lynch syndrome develop more than one cancer during their lifetime, often at a younger age than other people. When people know they have Lynch syndrome, they can have regular bowel checks (colonoscopies) to find and remove polyps before they develop into cancer. They can also protect themselves from womb cancer by having a hysterectomy once their family is complete. A diagnosis of Lynch syndrome can also allow family members to be tested and enrolled in cancer screening and prevention programmes, if they too test positive.
Screening people with bowel and womb cancers for Lynch syndrome
In the UK, the National Institute for Health and Care Excellence (NICE) recommends screening every person who develops bowel cancer for Lynch syndrome. It is thought that the proportion of womb cancers that are caused by Lynch syndrome is very similar to that of bowel, around one in thirty. Womb cancer is often the first cancer that a woman with Lynch syndrome develops, around five or more years before she develops bowel cancer.
There are no current guidelines that recommend screening women with womb cancer for Lynch syndrome. This represents a missed diagnostic opportunity because womb cancer presents early and has an excellent prognosis. Failing to diagnose Lynch syndrome denies her the opportunity to enrol in bowel cancer prevention and screening programmes, with knock on implications for her affected family members.
The Manchester International Consensus Meeting
The first two-day workshop that set out to define standards of care for the management of gynaecological cancers in Lynch syndrome was attended by more than 60 experts in genetics, gynaecology, pathology, epidemiology, screening and health economics, as well as healthcare professionals and patients with personal or professional experience of Lynch syndrome.
The aim of the workshop was to set standards of care that women with Lynch syndrome should expect and receive. We set out to answer four main questions:.
- Should we screen women with womb cancer for Lynch syndrome?
The group was unanimous in its view that all women with womb cancer should be screened for Lynch syndrome. Limiting screening to women of a certain age or with a particularly strong family history is flawed because it would miss between one and two thirds of all cases. Performing a tumour triage test, that is, looking for hallmarks of Lynch syndrome in the resected tumours, was supported as a means of reducing the costs and psychological burden of testing for the majority of women who do not have Lynch syndrome.
- How should we screen for Lynch syndrome?
Two tumour tests are of equal value in this regard: looking for loss of the mismatch repair proteins by a routine laboratory test called immunohistochemistry; or looking for DNA disarray, so-called microsatellite instability, which characterises Lynch syndrome tumours. Using either of these two tests reduces the number of women who need to undergo genetic testing for Lynch syndrome by filtering out the three-quarters of women who do not. This proportion can be reduced to just one in twenty women if a further tumour-based test is used to identify tumours caused by the non-hereditary ‘switching off’ of one of the mismatch repair genes.
- How do women with Lynch syndrome protect themselves from gynaecological cancer?
Hysterectomy and removal of the ovaries once a woman has completed her family prevents womb and ovarian cancer, but such a decision cannot be taken lightly. There are surgical and anaesthetic risks of preventative surgery, not to mention the hormonal consequences of an immediate and abrupt menopause in a woman of reproductive age. The need for hormone replacement therapy (HRT) to support bone and heart health until at least 50 years of age was emphasised. It was acknowledged that Lynch syndrome-associated gynaecological cancers present at an early stage, so it is unlikely that risk-reducing hysterectomy will save lives.
Taking aspirin, combined oral contraceptives (‘the pill’) and other hormones (Mirena coil, ‘mini-pill’, contraceptive injection), may also reduce the risk of gynaecological cancer in Lynch syndrome, but more research is needed. Other prevention strategies include maintaining a healthy body weight, being physically active, avoiding smoking and drinking alcohol in moderation if at all.
- Is there a role for gynaecological surveillance in Lynch syndrome?
The role for gynaecological screening for women with Lynch syndrome was unclear. Cervical screening is already recommended for every woman because it prevents cervical cancer. However, there is insufficient research to recommend screening for ovarian or womb cancers in women with Lynch syndrome. That is not to say that annual ultrasound scans, camera tests (hysteroscopy) and biopsies have no value, just that their value is unclear. The group urged the research community to make studying screening for Lynch syndrome-associated gynaecological cancers a priority so that women can make evidence-based choices in the future.