There is no evidence to support screening in the general population. Although the condition is common, it has a classical presentation (abnormal vaginal bleeding) and good prognosis with effective treatment (surgery). For all women, an enquiry should be made for peri-menopausal or post-menopausal vaginal bleeding during routine health checks.
ACOG: well-woman health care
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Women with personal history or a significant family history consistent with Lynch syndrome may benefit from genetic risk assessment. Identification of Lynch syndrome allows for risk-reduction strategies, surveillance for early detection, and cascade testing (counselling and testing of blood relatives of individuals identified with a specific genetic mutation).
Women with Lynch syndrome should be offered regular endometrial biopsy because of their high risk of endometrial cancer (lifetime risk 35% to 54% for the MLH1 variant; 21% to 57% for MSH2 and EPCAM; 16% to 49% for MSH6; 13% to 26% for PMS2) compared with the general population (3.1%).[81]National Comprehensive Cancer Network. NCCN clinical practice guidelines in oncology: genetic/familial high-risk assessment: colorectal, endometrial, and gastric [internet publication].
https://www.nccn.org/guidelines/category_2
[82]American College of Obstetricians and Gynecologists, Society of Gynecologic Oncology. ACOG practice bulletin no. 147: Lynch syndrome. Obstet Gynecol. 2014 Nov;124(5):1042-54.[97]Lancaster JM, Powell CB, Chen LM, et al; SGO Clinical Practice Committee. Society of Gynecologic Oncology statement on risk assessment for inherited gynecologic cancer predispositions. Gynecol Oncol. 2014 Sep 17;136(1):3-7. [Erratum in: Gynecol Oncol. 2015 Sep;138(3):765.]
http://www.ncbi.nlm.nih.gov/pubmed/25238946?tool=bestpractice.com
Screening for Lynch syndrome
A careful personal and family history may identify patients at increased risk of Lynch syndrome who should be offered genetic risk assessment (including counselling and genetic testing) for Lynch syndrome.[81]National Comprehensive Cancer Network. NCCN clinical practice guidelines in oncology: genetic/familial high-risk assessment: colorectal, endometrial, and gastric [internet publication].
https://www.nccn.org/guidelines/category_2
[82]American College of Obstetricians and Gynecologists, Society of Gynecologic Oncology. ACOG practice bulletin no. 147: Lynch syndrome. Obstet Gynecol. 2014 Nov;124(5):1042-54.
Criteria for evaluation of Lynch syndrome include:[81]National Comprehensive Cancer Network. NCCN clinical practice guidelines in oncology: genetic/familial high-risk assessment: colorectal, endometrial, and gastric [internet publication].
https://www.nccn.org/guidelines/category_2
Blood relative with a known Lynch syndrome pathogenic variant.
Personal history of a tumour with MMR deficiency.
Personal history of a Lynch syndrome-related cancer with diagnosis at age <50 years, or with a synchronous or metachronous related cancer, or with a strong family history of related cancer.
Family history including a first-degree relative with colorectal and/or endometrial cancer with diagnosis at age <50 years, or with a synchronous or metachronous Lynch syndrome-related cancer.
Family history including two or more first- or second-degree relatives with Lynch syndrome-related cancers.
Germline testing for a specific pathogenic variant can be carried out, if known; tailored germline multigene panel testing is recommended if the variant is unknown.[81]National Comprehensive Cancer Network. NCCN clinical practice guidelines in oncology: genetic/familial high-risk assessment: colorectal, endometrial, and gastric [internet publication].
https://www.nccn.org/guidelines/category_2
If Lynch syndrome is confirmed, offer timely cascade testing.[156]American College of Obstetricians and Gynecologists. ACOG committee opinion no. 727: cascade testing: testing women for known hereditary genetic mutations associated with cancer. Obstet Gynecol. 2018 Jan;131(1):e31-4.
https://journals.lww.com/greenjournal/Fulltext/2018/01000/ACOG_Committee_Opinion_No__727__Cascade_Testing_.40.aspx
http://www.ncbi.nlm.nih.gov/pubmed/29266077?tool=bestpractice.com
Surveillance for women with Lynch syndrome
Endometrial biopsy every 1 or 2 years, starting at age 30 to 35 years, may be considered for women with Lynch syndrome.[81]National Comprehensive Cancer Network. NCCN clinical practice guidelines in oncology: genetic/familial high-risk assessment: colorectal, endometrial, and gastric [internet publication].
https://www.nccn.org/guidelines/category_2
[82]American College of Obstetricians and Gynecologists, Society of Gynecologic Oncology. ACOG practice bulletin no. 147: Lynch syndrome. Obstet Gynecol. 2014 Nov;124(5):1042-54. Biopsy has high diagnostic accuracy, but benefit from screening has not been proven.
Transvaginal ultrasound may be considered in post-menopausal patients with Lynch syndrome, although it lacks diagnostic accuracy.[82]American College of Obstetricians and Gynecologists, Society of Gynecologic Oncology. ACOG practice bulletin no. 147: Lynch syndrome. Obstet Gynecol. 2014 Nov;124(5):1042-54. Transvaginal ultrasound is not recommended in premenopausal patients because of variation in endometrial stripe thickness during the menstrual cycle.[81]National Comprehensive Cancer Network. NCCN clinical practice guidelines in oncology: genetic/familial high-risk assessment: colorectal, endometrial, and gastric [internet publication].
https://www.nccn.org/guidelines/category_2
Women with Lynch syndrome may benefit from a prophylactic, risk-reducing hysterectomy after completion of childbearing.[39]Koornstra JJ, Mourits MJ, Sijmons RH, et al. Management of extracolonic tumours in patients with Lynch syndrome. Lancet Oncol. 2009 Apr;10(4):400-8.
http://www.ncbi.nlm.nih.gov/pubmed/19341971?tool=bestpractice.com
[40]Barrow E, Robinson L, Alduaij W, et al. Cumulative lifetime incidence of extracolonic cancers in Lynch syndrome: a report of 121 families with proven mutations. Clin Genet. 2009 Feb;75(2):141-9.
http://www.ncbi.nlm.nih.gov/pubmed/19215248?tool=bestpractice.com
[82]American College of Obstetricians and Gynecologists, Society of Gynecologic Oncology. ACOG practice bulletin no. 147: Lynch syndrome. Obstet Gynecol. 2014 Nov;124(5):1042-54.[96]Crosbie EJ, Kitson SJ, McAlpine JN, et al. Endometrial cancer. Lancet. 2022 Apr 9;399(10333):1412-28.
http://www.ncbi.nlm.nih.gov/pubmed/35397864?tool=bestpractice.com
[97]Lancaster JM, Powell CB, Chen LM, et al; SGO Clinical Practice Committee. Society of Gynecologic Oncology statement on risk assessment for inherited gynecologic cancer predispositions. Gynecol Oncol. 2014 Sep 17;136(1):3-7. [Erratum in: Gynecol Oncol. 2015 Sep;138(3):765.]
http://www.ncbi.nlm.nih.gov/pubmed/25238946?tool=bestpractice.com
[157]Lancaster JM, Powell CB, Kauff ND, et al. Society of Gynecologic Oncologists Education Committee statement on risk assessment for inherited gynecologic cancer predispositions. Gynecol Oncol. 2007 Nov;107(2):159-62.
http://www.ncbi.nlm.nih.gov/pubmed/17950381?tool=bestpractice.com
Prophylactic bilateral salpingo-oophorectomy (BSO) may also be beneficial because of the high risk of ovarian cancer associated with some Lynch syndrome mutations.[81]National Comprehensive Cancer Network. NCCN clinical practice guidelines in oncology: genetic/familial high-risk assessment: colorectal, endometrial, and gastric [internet publication].
https://www.nccn.org/guidelines/category_2
[82]American College of Obstetricians and Gynecologists, Society of Gynecologic Oncology. ACOG practice bulletin no. 147: Lynch syndrome. Obstet Gynecol. 2014 Nov;124(5):1042-54.[98]Schmeler KM, Lynch HT, Chen LM, et al. Prophylactic surgery to reduce the risk of gynecologic cancers in the Lynch syndrome. N Engl J Med. 2006 Jan 19;354(3):261-9.
https://www.nejm.org/doi/full/10.1056/NEJMoa052627
http://www.ncbi.nlm.nih.gov/pubmed/16421367?tool=bestpractice.com
See Primary prevention.
Surveillance for women treated with tamoxifen
Risk of endometrial cancer is increased (two- to sevenfold) in post-menopausal women treated with tamoxifen for breast cancer.[71]Emons G, Mustea A, Tempfer C. Tamoxifen and endometrial cancer: a Janus-headed drug. Cancers (Basel). 2020 Sep 7;12(9):2535.
https://www.mdpi.com/2072-6694/12/9/2535
http://www.ncbi.nlm.nih.gov/pubmed/32906618?tool=bestpractice.com
[72]American College of Obstetricians and Gynecologists. ACOG committee opinion no. 601: tamoxifen and uterine cancer. Jun 2014 [internet publication].
https://www.acog.org/clinical/clinical-guidance/committee-opinion/articles/2014/06/tamoxifen-and-uterine-cancer
http://www.ncbi.nlm.nih.gov/pubmed/24848920?tool=bestpractice.com
Risk increases with duration of use. Tamoxifen-associated endometrial cancer may be associated with worse prognosis due to less favourable histology and higher stage at diagnosis.[71]Emons G, Mustea A, Tempfer C. Tamoxifen and endometrial cancer: a Janus-headed drug. Cancers (Basel). 2020 Sep 7;12(9):2535.
https://www.mdpi.com/2072-6694/12/9/2535
http://www.ncbi.nlm.nih.gov/pubmed/32906618?tool=bestpractice.com
[73]Magriples U, Naftolin F, Schwartz PE, et al. High-grade endometrial carcinoma in tamoxifen-treated breast cancer patients. J Clin Oncol. 1993 Mar;11(3):485-90.
http://www.ncbi.nlm.nih.gov/pubmed/8383191?tool=bestpractice.com
[74]Ferguson SE, Soslow RA, Amsterdam A, et al. Comparison of uterine malignancies that develop during and following tamoxifen therapy. Gynecol Oncol. 2006 May;101(2):322-6.
http://www.ncbi.nlm.nih.gov/pubmed/16352333?tool=bestpractice.com
[75]Bergman L, Beelen ML, Gallee MP, et al. Risk and prognosis of endometrial cancer after tamoxifen for breast cancer. Comprehensive Cancer Centres' ALERT Group. Assessment of liver and endometrial cancer risk following tamoxifen. Lancet. 2000 Sep 9;356(9233):881-7.
http://www.ncbi.nlm.nih.gov/pubmed/11036892?tool=bestpractice.com
[76]Hoogendoorn WE, Hollema H, van Boven HH, et al. Prognosis of uterine corpus cancer after tamoxifen treatment for breast cancer. Breast Cancer Res Treat. 2008 Nov;112(1):99-108.
http://www.ncbi.nlm.nih.gov/pubmed/18064567?tool=bestpractice.com
Post-menopausal women taking tamoxifen should be closely monitored for symptoms and advised to promptly report any abnormal vaginal bleeding.[72]American College of Obstetricians and Gynecologists. ACOG committee opinion no. 601: tamoxifen and uterine cancer. Jun 2014 [internet publication].
https://www.acog.org/clinical/clinical-guidance/committee-opinion/articles/2014/06/tamoxifen-and-uterine-cancer
http://www.ncbi.nlm.nih.gov/pubmed/24848920?tool=bestpractice.com
[74]Ferguson SE, Soslow RA, Amsterdam A, et al. Comparison of uterine malignancies that develop during and following tamoxifen therapy. Gynecol Oncol. 2006 May;101(2):322-6.
http://www.ncbi.nlm.nih.gov/pubmed/16352333?tool=bestpractice.com
Routine endometrial surveillance has not been found to increase early detection of endometrial cancer in post-menopausal tamoxifen users who are not at high risk for endometrial cancer.[71]Emons G, Mustea A, Tempfer C. Tamoxifen and endometrial cancer: a Janus-headed drug. Cancers (Basel). 2020 Sep 7;12(9):2535.
https://www.mdpi.com/2072-6694/12/9/2535
http://www.ncbi.nlm.nih.gov/pubmed/32906618?tool=bestpractice.com
[158]Fung MF, Reid A, Faught W, et al. Prospective longitudinal study of ultrasound screening for endometrial abnormalities in women with breast cancer receiving tamoxifen. Gynecol Oncol. 2003 Oct;91(1):154-9.
http://www.ncbi.nlm.nih.gov/pubmed/14529676?tool=bestpractice.com
[159]Love CD, Muir BB, Scrimgeour JB, et al. Investigation of endometrial abnormalities in asymptomatic women treated with tamoxifen and an evaluation of the role of endometrial screening. J Clin Oncol. 1999 Jul;17(7):2050-4.
http://www.ncbi.nlm.nih.gov/pubmed/10561257?tool=bestpractice.com
Such surveillance may lead to more invasive and costly diagnostic procedures and is not, therefore, recommended.[72]American College of Obstetricians and Gynecologists. ACOG committee opinion no. 601: tamoxifen and uterine cancer. Jun 2014 [internet publication].
https://www.acog.org/clinical/clinical-guidance/committee-opinion/articles/2014/06/tamoxifen-and-uterine-cancer
http://www.ncbi.nlm.nih.gov/pubmed/24848920?tool=bestpractice.com
[160]Demirkiran F, Arvas M, Erkun E, et al. The prognostic significance of cervico-vaginal cytology in endometrial cancer. Eur J Gynaecol Oncol. 1995;16(5):403-9.
http://www.ncbi.nlm.nih.gov/pubmed/8549608?tool=bestpractice.com
[161]Bristow RE, Purinton SC, Santillan A, et al. Cost-effectiveness of routine vaginal cytology for endometrial cancer surveillance. Gynecol Oncol. 2006 Nov;103(2):709-13.
http://www.ncbi.nlm.nih.gov/pubmed/16797686?tool=bestpractice.com
[162]Wolfman W, Bougie O, Chen I, et al. Guideline no. 451: asymptomatic endometrial thickening in postmenopausal women. J Obstet Gynaecol Can. 2024 Jul;46(7):102591.
http://www.ncbi.nlm.nih.gov/pubmed/38901794?tool=bestpractice.com
No clear survival advantage has been demonstrated with ultrasound screening over clinical surveillance for post-menopausal vaginal bleeding.[74]Ferguson SE, Soslow RA, Amsterdam A, et al. Comparison of uterine malignancies that develop during and following tamoxifen therapy. Gynecol Oncol. 2006 May;101(2):322-6.
http://www.ncbi.nlm.nih.gov/pubmed/16352333?tool=bestpractice.com
Ultrasound may have a role prior to commencing tamoxifen to identify pre-existing benign lesions.[70]Neven P, De Muylder X, Van Belle Y, et al. Longitudinal hysteroscopic follow-up during tamoxifen treatment. Lancet. 1998 Jan 3;351(9095):36.
http://www.ncbi.nlm.nih.gov/pubmed/9433432?tool=bestpractice.com
[74]Ferguson SE, Soslow RA, Amsterdam A, et al. Comparison of uterine malignancies that develop during and following tamoxifen therapy. Gynecol Oncol. 2006 May;101(2):322-6.
http://www.ncbi.nlm.nih.gov/pubmed/16352333?tool=bestpractice.com
[163]Garuti G, Grossi F, Centinaio G, et al. Pretreatment and prospective assessment of endometrium in menopausal women taking tamoxifen for breast cancer. Eur J Obstet Gynecol Reprod Biol. 2007 May;132(1):101-6.
http://www.ncbi.nlm.nih.gov/pubmed/16678960?tool=bestpractice.com
Pre-menopausal women treated with tamoxifen have no increased risk of endometrial cancer and, as such, require no additional monitoring beyond routine gynaecological care.[72]American College of Obstetricians and Gynecologists. ACOG committee opinion no. 601: tamoxifen and uterine cancer. Jun 2014 [internet publication].
https://www.acog.org/clinical/clinical-guidance/committee-opinion/articles/2014/06/tamoxifen-and-uterine-cancer
http://www.ncbi.nlm.nih.gov/pubmed/24848920?tool=bestpractice.com