Should women with Lynch syndrome be offered gynaecological cancer surveillance?

Ryan, Neil; Snowsill, Tristan; McKenzie, EJ; Monahan, Kevin; Nebgen, Denise R.

doi:10.1136/bmj.n2020

Cited by 7 publications

(7 citation statements)

References 33 publications

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“…Lifetime risk of endometrial cancer is between 20% and 70% for MLH1, MSH2, MSH6 variant carriers, and 10% and 15% for PMS2 variant carriers, with a lesser but nevertheless increased risk of ovarian cancer. However, endometrial or ovarian cancer surveillance does not reduce mortality in LS 31 32. The typical age of onset of gynaecological cancer in LS is after age 40 years (with 5% patients younger than 40 years); therefore, women should be counselled on consideration of risk-reducing hysterectomy and removal of ovaries at age 40 years (for MLH1 , MSH2 and MSH6 variant carriers).…”

Section: Introductionmentioning

confidence: 99%

Diagnosis and management of Lynch syndrome

Edwards

Monahan

2022

Frontline Gastroenterol

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Lynch syndrome (LS) is a dominantly inherited cancer susceptibility syndrome defined by presence of pathogenic variants in DNA mismatch repair genes MLH1, MSH2, MSH6 and PMS2, or in deletions of the EPCAM gene. Although LS is present in about 1 in 400 people in the UK, it estimated that only 5% of people with this condition are aware of the diagnosis. Therefore, testing for LS in all new diagnoses of colorectal or endometrial cancers is now recommended in the UK, and gastroenterologists can offer ‘mainstreamed’ genetic testing for LS to patients with cancer. Because LS results in a high lifetime risk of colorectal, endometrial, gastric, ovarian, hepatobiliary, brain and other cancers, the lifelong care of affected individuals and their families requires a coordinated multidisciplinary approach. Interventions such as high-quality 2-yearly colonoscopy, prophylactic gynaecological surgery, and aspirin are proven to prevent and facilitate early diagnosis and prevention of cancers in this population, and improve patient outcomes. Recently, an appreciation of the mechanism of carcinogenesis in LS-associated cancers has contributed to the development of novel therapeutic and diagnostic approaches, with a gene-specific approach to disease management, with potential cancer-preventing vaccines in development. An adaptive approach to surgical or oncological management of LS-related cancers may be considered, including an important role for novel checkpoint inhibitor immunotherapy in locally advanced or metastatic disease. Therefore, a personalised approach to lifelong gene-specific management for people with LS provides many opportunities for cancer prevention and treatment which we outline in this review.

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Section: Introductionmentioning

confidence: 99%

Diagnosis and management of Lynch syndrome

Edwards

Monahan

2022

Frontline Gastroenterol

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“…Hysterectomy is advised for women with Lynch syndrome where endometrial cancer risk is significantly elevated and the efficacy of screening is uncertain. 5,19 Decision-making about hysterectomy at the time of RRSO for BRCA1 and BRCA2 is more complex. Two systematic reviews and meta-analyses on endometrial cancer risk in BRCA1 and BRCA2 carriers show a slight increased relative risk of serous endometrial cancer in BRCA1 (Standardised Incidence Ratio 2.81) and BRCA2 (Standardised Incidence Ratio 1.75) 20,21 but minimal increase in absolute risk.…”

Section: Discussion Of Concurrent Hysterectomy At Rrsomentioning

confidence: 99%

Care after premenopausal risk‐reducing salpingo‐oophorectomy in high‐risk women: Scoping review and international consensus recommendations

Nebgen

Domchek

Kotsopoulos

et al. 2023

BJOG

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Women at high inherited risk of ovarian cancer are offered risk‐reducing salpingo‐oophorectomy (RRSO) from age 35 to 45 years. Although potentially life‐saving, RRSO may induce symptoms that negatively affect quality of life and impair long‐term health. Clinical care following RRSO is often suboptimal. This scoping review describes how RRSO affects short‐ and long‐term health and provides evidence‐based international consensus recommendations for care from preoperative counselling to long‐term disease prevention. This includes the efficacy and safety of hormonal and non‐hormonal treatments for vasomotor symptoms, sleep disturbance and sexual dysfunction and effective approaches to prevent bone and cardiovascular disease.

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“…The role of gynaecological cancer surveillance in women with LS has been discussed in detail. 72 There is no good evidence to support its use. However, such surveillance is offered in the United Kingdom albeit in an ad hoc fashion.…”

Section: Cancer Risk Reductionmentioning

confidence: 99%

“… 101 For women there is currently no method that can be reliably used to detect either ovarian cancer or endometrial cancer. 72 …”

Section: The Futurementioning

confidence: 99%

A Focused Clinical Review of Lynch Syndrome

Georgiou¹,

Monje-Garcia²,

Miles³

et al. 2023

CMAR

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Lynch syndrome (LS) is an autosomal dominant condition that increases an individual’s risk of a constellation of cancers. LS is defined when an individual has inherited pathogenic variants in the mismatch repair genes. Currently, most people with LS are undiagnosed. Early detection of LS is vital as those with LS can be enrolled in cancer reduction strategies through chemoprophylaxis, risk reducing surgery and cancer surveillance. However, these interventions are often invasive and require refinement. Furthermore, not all LS associated cancers are currently amenable to surveillance. Historically only those with a strong family history suggestive of LS were offered testing; this has proved far too restrictive. New criteria for testing have recently been introduced including the universal screening for LS in associated cancers. This has increased the number of people being diagnosed with LS but has also brought about unique challenges such as when to consent for germline testing and questions over how and who should carry out the consent. The results of germline testing for LS can be complicated and the diagnostic pathway is not always clear. Furthermore, by testing only those with cancer for LS we fail to identify these individuals before they develop potentially fatal pathology. This review will outline these challenges and explore solutions. Furthermore, we consider the potential future of LS care and the related treatments and interventions which are the current focus of research.

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Should women with Lynch syndrome be offered gynaecological cancer surveillance?

Cited by 7 publications

References 33 publications

Diagnosis and management of Lynch syndrome

Diagnosis and management of Lynch syndrome

Care after premenopausal risk‐reducing salpingo‐oophorectomy in high‐risk women: Scoping review and international consensus recommendations

A Focused Clinical Review of Lynch Syndrome

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