Endometrial and Ovarian Cancer in Lynch Syndrome

 

 Buy Article Permissions and Reprints

Abstract

Lynch syndrome (LS) is an autosomal dominant familial cancer risk syndrome that occurs due to a germline mutation in one of several mismatch repair genes and is associated with an increased risk of colorectal, endometrial, and ovarian cancer. The risk of endometrial cancer equals or exceeds that of colorectal cancer in women with LS. The diagnosis of gynecologic cancer precedes that of colorectal cancer in over half of women with metachronous gynecologic and colon cancers, making gynecologic cancer a “sentinel cancer” for LS. There are no studies addressing the effectiveness or safety of chemoprevention for women with LS. Surveillance with gynecologic examination including assessment of symptoms, transvaginal pelvic ultrasonography, endometrial biopsy, and CA125 tumor marker assessment can be offered, but has not been shown to improve outcomes for these patients. Prophylactic hysterectomy with bilateral salpingo-oophorectomy performed after the completion of childbearing may be offered for gynecologic cancer prevention.

• References

• 1 Lynch HT, Shaw MW, Magnuson CW, Larsen AL, Krush AJ. Hereditary factors in cancer. Study of two large midwestern kindreds. Arch Intern Med 1966; 117 (2) 206-212
  CrossrefPubMedGoogle Scholar
• 2 Aarnio M, Sankila R, Pukkala E , et al. Cancer risk in mutation carriers of DNA-mismatch-repair genes. Int J Cancer 1999; 81 (2) 214-218
  CrossrefPubMedGoogle Scholar
• 3 Dunlop MG, Farrington SM, Carothers AD , et al. Cancer risk associated with germline DNA mismatch repair gene mutations. Hum Mol Genet 1997; 6 (1) 105-110
  CrossrefPubMedGoogle Scholar
• 4 Lu KH, Dinh M, Kohlmann W , et al. Gynecologic cancer as a “sentinel cancer” for women with hereditary nonpolyposis colorectal cancer syndrome. Obstet Gynecol 2005; 105 (3) 569-574
  CrossrefPubMedGoogle Scholar
• 5 American College of Obstetricians and Gynecologists. ACOG practice bulletin, clinical management guidelines for obstetrician-gynecologists, number 65, August 2005: management of endometrial cancer. Obstet Gynecol 2005; 106 (2) 413-425
  CrossrefPubMedGoogle Scholar
• 6 Howlader N, Noone AM, Krapcho M , et al, eds. SEER Cancer Statistics Review, 1975–2008. Bethesda, MD: National Cancer Institute; . Available at: http://seer.cancer.gov/csr/1975_2008/ . Accessed September 7, 2011
  Google Scholar
• 7 Vasen HF, Watson P, Mecklin JP , et al. The epidemiology of endometrial cancer in hereditary nonpolyposis colorectal cancer. Anticancer Res 1994; 14 (4B) 1675-1678
  PubMedGoogle Scholar
• 8 Boks DE, Trujillo AP, Voogd AC, Morreau H, Kenter GG, Vasen HF. Survival analysis of endometrial carcinoma associated with hereditary nonpolyposis colorectal cancer. Int J Cancer 2002; 102 (2) 198-200
  CrossrefPubMedGoogle Scholar
• 9 Broaddus RR, Lynch HT, Chen LM , et al. Pathologic features of endometrial carcinoma associated with HNPCC: a comparison with sporadic endometrial carcinoma. Cancer 2006; 106 (1) 87-94
  CrossrefPubMedGoogle Scholar
• 10 Carcangiu ML, Radice P, Casalini P, Bertario L, Merola M, Sala P. Lynch syndrome-related endometrial carcinomas show a high frequency of nonendometrioid types and of high FIGO grade endometrioid types. Int J Surg Pathol 2010; 18 (1) 21-26
  CrossrefPubMedGoogle Scholar
• 11 Westin SN, Lacour RA, Urbauer DL , et al. Carcinoma of the lower uterine segment: a newly described association with Lynch syndrome. J Clin Oncol 2008; 26 (36) 5965-5971
  CrossrefPubMedGoogle Scholar
• 12 Hachisuga T, Kaku T, Enjoji M. Carcinoma of the lower uterine segment. Clinicopathologic analysis of 12 cases. Int J Gynecol Pathol 1989; 8 (1) 26-35
  CrossrefPubMedGoogle Scholar
• 13 Jacques SM, Qureshi F, Ramirez NC, Malviya VK, Lawrence WD. Tumors of the uterine isthmus: clinicopathologic features and immunohistochemical characterization of p53 expression and hormone receptors. Int J Gynecol Pathol 1997; 16 (1) 38-44
  CrossrefPubMedGoogle Scholar
• 14 Greer BE, Koh W-J, Abu-Rustum NR , et al. NCCN clinical practice guidelines in oncology. Uterine neoplasms. Version 1. 2012. Available at: http://www.nccn.org/professionals/physician_gls/pdf/uterine.pdf . Accessed September 4, 2011
  PubMedGoogle Scholar
• 15 Burt RW, Barthel JS, Cannon J , et al. NCCN clinical practice guidelines in oncology. Colorectal cancer screening. Version 2. 2011 Available at: http://www.nccn.org/professionals/physician_gls/pdf/colorectal_screening.pdf . Accessed September 4, 2011
  PubMed
• 16 Evaluation of Genomic Applications in Practice and Prevention (EGAPP) Working Group. Recommendations from the EGAPP Working Group: genetic testing strategies in newly diagnosed individuals with colorectal cancer aimed at reducing morbidity and mortality from Lynch syndrome in relatives. Genet Med 2009; 11 (1) 35-41
  CrossrefPubMedGoogle Scholar
• 17 Watson P, Vasen HF, Mecklin JP , et al. The risk of extra-colonic, extra-endometrial cancer in the Lynch syndrome. Int J Cancer 2008; 123 (2) 444-449
  CrossrefPubMedGoogle Scholar
• 18 Ketabi Z, Bartuma K, Bernstein I , et al. Ovarian cancer linked to Lynch syndrome typically presents as early-onset, non-serous epithelial tumors. Gynecol Oncol 2011; 121 (3) 462-465
  CrossrefPubMedGoogle Scholar
• 19 Grindedal EM, Renkonen-Sinisalo L, Vasen H , et al. Survival in women with MMR mutations and ovarian cancer: a multicentre study in Lynch syndrome kindreds. J Med Genet 2010; 47 (2) 99-102
  CrossrefPubMedGoogle Scholar
• 20 Watson P, Bützow R, Lynch HT , et al; International Collaborative Group on HNPCC. The clinical features of ovarian cancer in hereditary nonpolyposis colorectal cancer. Gynecol Oncol 2001; 82 (2) 223-228
  CrossrefPubMedGoogle Scholar
• 21 Crijnen TE, Janssen-Heijnen ML, Gelderblom H , et al. Survival of patients with ovarian cancer due to a mismatch repair defect. Fam Cancer 2005; 4 (4) 301-305
  CrossrefPubMedGoogle Scholar
• 22 Singh N. Synchronous tumours of the female genital tract. Histopathology 2010; 56 (3) 277-285
  CrossrefPubMedGoogle Scholar
• 23 Evans-Metcalf ER, Brooks SE, Reale FR, Baker SP. Profile of women 45 years of age and younger with endometrial cancer. Obstet Gynecol 1998; 91 (3) 349-354
  CrossrefPubMedGoogle Scholar
• 24 Tran BN, Connell PP, Waggoner S, Rotmensch J, Mundt AJ. Characteristics and outcome of endometrial carcinoma patients age 45 years and younger. Am J Clin Oncol 2000; 23 (5) 476-480
  CrossrefPubMedGoogle Scholar
• 25 Gitsch G, Hanzal E, Jensen D, Hacker NF. Endometrial cancer in premenopausal women 45 years and younger. Obstet Gynecol 1995; 85 (4) 504-508
  CrossrefPubMedGoogle Scholar
• 26 Soliman PT, Oh JC, Schmeler KM , et al. Risk factors for young premenopausal women with endometrial cancer. Obstet Gynecol 2005; 105 (3) 575-580
  CrossrefPubMedGoogle Scholar
• 27 Soliman PT, Broaddus RR, Schmeler KM , et al. Women with synchronous primary cancers of the endometrium and ovary: do they have Lynch syndrome?. J Clin Oncol 2005; 23 (36) 9344-9350
  CrossrefPubMedGoogle Scholar
• 28 The Cancer and Steroid Hormone Study of the Centers for Disease Control and the National Institute of Child Health and Human Development. Combination oral contraceptive use and the risk of endometrial cancer. JAMA 1987; 257 (6) 796-800
  CrossrefPubMedGoogle Scholar
• 29 The Cancer and Steroid Hormone Study of the Centers for Disease Control and the National Institute of Child Health and Human Development. The reduction in risk of ovarian cancer associated with oral-contraceptive use. N Engl J Med 1987; 316 (11) 650-655
  CrossrefPubMedGoogle Scholar
• 30 Modan B, Hartge P, Hirsh-Yechezkel G , et al; National Israel Ovarian Cancer Study Group. Parity, oral contraceptives, and the risk of ovarian cancer among carriers and noncarriers of a BRCA1 or BRCA2 mutation. N Engl J Med 2001; 345 (4) 235-240
  CrossrefPubMedGoogle Scholar
• 31 Narod SA, Risch H, Moslehi R , et al; Hereditary Ovarian Cancer Clinical Study Group. Oral contraceptives and the risk of hereditary ovarian cancer. N Engl J Med 1998; 339 (7) 424-428
  CrossrefPubMedGoogle Scholar
• 32 Whittemore AS, Balise RR, Pharoah PD , et al. Oral contraceptive use and ovarian cancer risk among carriers of BRCA1 or BRCA2 mutations. Br J Cancer 2004; 91 (11) 1911-1915
  CrossrefPubMedGoogle Scholar
• 33 McGuire V, Felberg A, Mills M , et al. Relation of contraceptive and reproductive history to ovarian cancer risk in carriers and noncarriers of BRCA1 gene mutations. Am J Epidemiol 2004; 160 (7) 613-618
  CrossrefPubMedGoogle Scholar
• 34 McLaughlin JR, Risch HA, Lubinski J , et al; Hereditary Ovarian Cancer Clinical Study Group. Reproductive risk factors for ovarian cancer in carriers of BRCA1 or BRCA2 mutations: a case-control study. Lancet Oncol 2007; 8 (1) 26-34
  CrossrefPubMedGoogle Scholar
• 35 Antoniou AC, Rookus M, Andrieu N , et al; EMBRACE; GENEPSO; GEO-HEBON. Reproductive and hormonal factors, and ovarian cancer risk for BRCA1 and BRCA2 mutation carriers: results from the International BRCA1/2 Carrier Cohort Study. Cancer Epidemiol Biomarkers Prev 2009; 18 (2) 601-610
  CrossrefPubMedGoogle Scholar
• 36 Milne RL, Knight JA, John EM , et al. Oral contraceptive use and risk of early-onset breast cancer in carriers and noncarriers of BRCA1 and BRCA2 mutations. Cancer Epidemiol Biomarkers Prev 2005; 14 (2) 350-356
  CrossrefPubMedGoogle Scholar
• 37 Haile RW, Thomas DC, McGuire V , et al; kConFab Investigators; Ontario Cancer Genetics Network Investigators. BRCA1 and BRCA2 mutation carriers, oral contraceptive use, and breast cancer before age 50. Cancer Epidemiol Biomarkers Prev 2006; 15 (10) 1863-1870
  CrossrefPubMedGoogle Scholar
• 38 Brohet RM, Goldgar DE, Easton DF , et al. Oral contraceptives and breast cancer risk in the international BRCA1/2 carrier cohort study: a report from EMBRACE, GENEPSO, GEO-HEBON, and the IBCCS Collaborating Group. J Clin Oncol 2007; 25 (25) 3831-3836
  CrossrefPubMedGoogle Scholar
• 39 Buys SS, Partridge E, Black A , et al; PLCO Project Team. Effect of screening on ovarian cancer mortality: the Prostate, Lung, Colorectal, and Ovarian (PLCO) Cancer Screening Randomized Controlled Trial. JAMA 2011; 305 (22) 2295-2303
  CrossrefPubMedGoogle Scholar
• 40 American College of Obstetricians and Gynecologists Committee on Gynecologic Practice. Committee Opinion No. 477: the role of the obstetrician-gynecologist in the early detection of epithelial ovarian cancer. Obstet Gynecol 2011; 117 (3) 742-746
  CrossrefPubMedGoogle Scholar
• 41 van der Velde NM, Mourits MJ, Arts HJ , et al. Time to stop ovarian cancer screening in BRCA1/2 mutation carriers?. Int J Cancer 2009; 124 (4) 919-923
  CrossrefPubMedGoogle Scholar
• 42 Gaarenstroom KN, van der Hiel B, Tollenaar RA , et al. Efficacy of screening women at high risk of hereditary ovarian cancer: results of an 11-year cohort study. Int J Gynecol Cancer 2006; 16 (Suppl 1) 54-59
  CrossrefPubMedGoogle Scholar
• 43 Olivier RI, Lubsen-Brandsma MA, Verhoef S, van Beurden M. CA125 and transvaginal ultrasound monitoring in high-risk women cannot prevent the diagnosis of advanced ovarian cancer. Gynecol Oncol 2006; 100 (1) 20-26
  CrossrefPubMedGoogle Scholar
• 44 Smith RA, Cokkinides V, Brooks D, Saslow D, Shah M, Brawley OW. Cancer screening in the United States, 2011: A review of current American Cancer Society guidelines and issues in cancer screening. CA Cancer J Clin 2011; 61 (1) 8-30
  CrossrefPubMedGoogle Scholar
• 45 Lindor NM, Petersen GM, Hadley DW , et al. Recommendations for the care of individuals with an inherited predisposition to Lynch syndrome: a systematic review. JAMA 2006; 296 (12) 1507-1517
  CrossrefPubMedGoogle Scholar
• 46 de Jong AE, Hendriks YM, Kleibeuker JH , et al. Decrease in mortality in Lynch syndrome families because of surveillance. Gastroenterology 2006; 130 (3) 665-671
  CrossrefPubMedGoogle Scholar
• 47 Dove-Edwin I, Boks D, Goff S , et al. The outcome of endometrial carcinoma surveillance by ultrasound scan in women at risk of hereditary nonpolyposis colorectal carcinoma and familial colorectal carcinoma. Cancer 2002; 94 (6) 1708-1712
  CrossrefPubMedGoogle Scholar
• 48 Rijcken FE, Mourits MJ, Kleibeuker JH, Hollema H, van der Zee AG. Gynecologic screening in hereditary nonpolyposis colorectal cancer. Gynecol Oncol 2003; 91 (1) 74-80
  CrossrefPubMedGoogle Scholar
• 49 Renkonen-Sinisalo L, Bützow R, Leminen A, Lehtovirta P, Mecklin JP, Järvinen HJ. Surveillance for endometrial cancer in hereditary nonpolyposis colorectal cancer syndrome. Int J Cancer 2007; 120 (4) 821-824
  CrossrefPubMedGoogle Scholar
• 50 Huang M, Sun C, Boyd-Rogers S , et al. Prospective study of combined colon and endometrial cancer screening in women with Lynch syndrome: a patient-centered approach. J Oncol Pract 2011; 7 (1) 43-47
  CrossrefPubMedGoogle Scholar
• 51 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; 354 (3) 261-269
  CrossrefPubMedGoogle Scholar
• 52 Johns DA, Carrera B, Jones J, DeLeon F, Vincent R, Safely C. The medical and economic impact of laparoscopically assisted vaginal hysterectomy in a large, metropolitan, not-for-profit hospital. Am J Obstet Gynecol 1995; 172 (6) 1709-1715 , discussion 1715–1719
  CrossrefPubMedGoogle Scholar
• 53 Schmeler KM, Daniels MS, Soliman PT , et al. Primary peritoneal cancer after bilateral salpingo-oophorectomy in two patients with Lynch syndrome. Obstet Gynecol 2010; 115 (2 Pt 2) 432-434
  CrossrefPubMedGoogle Scholar