Prophylactic Surgery to Reduce the Risk of Gynecologic Cancers in the Lynch Syndrome
Kathleen M. Schmeler, M.D., Henry T. Lynch, M.D., Lee-may Chen, M.D., Mark F. Munsell, M.S., Pamela T. Soliman, M.D., Mary Beth Clark, M.S.W., Molly S. Daniels, M.S., Kristin G. White, B.S., Stephanie G. Boyd-Rogers, R.N., Peggy G. Conrad, M.S., Kathleen Y. Yang, M.D., Mary M. Rubin, Ph.D., Charlotte C. Sun, Dr.P.H., Brian M. Slomovitz, M.D., David M. Gershenson, M.D., and Karen H. Lu, M.D.
Background Women with the Lynch syndrome (hereditary nonpolyposiscolorectal cancer) have a 40 to 60 percent lifetime risk ofendometrial cancer and a 10 to 12 percent lifetime risk of ovariancancer. The benefit of prophylactic gynecologic surgery forwomen with this syndrome has been uncertain. We designed thisstudy to determine the reduction in the risk of gynecologiccancers associated with prophylactic hysterectomy and bilateralsalpingo-oophorectomy in women with the Lynch syndrome.
Methods Three hundred fifteen women with documented germ-linemutations associated with the Lynch syndrome were identified.Women who had undergone prophylactic hysterectomy (61 women)and women who had undergone prophylactic bilateral salpingo-oophorectomy(47 women) were matched with mutation-positive women who hadnot undergone the procedure in question (210 women for the analysisof endometrial cancer and 223 for the analysis of ovarian cancer).Women who had undergone prophylactic surgery and their matchedcontrols were followed from the date of the surgery until theoccurrence of cancer or until the data were censored at thetime of the last follow-up visit.
Results There were no occurrences of endometrial, ovarian, orprimary peritoneal cancer among the women who had undergoneprophylactic surgery. Endometrial cancer was diagnosed in 69women in the control group (33 percent), for an incidence densityof 0.045 per woman-year, yielding a prevented fraction (theproportion of potential new cancers prevented) of 100 percent(95 percent confidence interval, 90 to 100 percent). Ovariancancer was diagnosed in 12 women in the control group (5 percent),for an incidence density of 0.005 per woman-year, yielding aprevented fraction of 100 percent (95 percent confidence interval,62 to 100 percent).
Conclusions These findings suggest that prophylactic hysterectomywith bilateral salpingo-oophorectomy is an effective strategyfor preventing endometrial and ovarian cancer in women withthe Lynch syndrome.
Source Information
From the Departments of Gynecologic Oncology (K.M.S., P.T.S., K.G.W., S.G.B.-R., C.C.S., B.M.S., D.M.G., K.H.L.), Biostatistics and Applied Mathematics (M.F.M.), and Clinical Cancer Genetics (M.S.D.), the University of Texas M.D. Anderson Cancer Center, Houston; the Department of Preventive Medicine, Creighton University, Omaha, Nebr. (H.T.L., M.B.C.); and the Departments of Gynecologic Oncology (L.C., K.Y.Y., M.M.R.) and Medicine (P.G.C.), University of California at San Francisco, San Francisco.
Address reprint requests to Dr. Lu at the Department of Gynecologic Oncology, University of Texas M.D. Anderson Cancer Center, P.O. Box 301439, Unit 1362, Houston, TX 77230-1439, or at khlu{at}mdanderson.org.
Jarvinen, H. J., Renkonen-Sinisalo, L., Aktan-Collan, K., Peltomaki, P., Aaltonen, L. A., Mecklin, J.-P.
(2009). Ten Years After Mutation Testing for Lynch Syndrome: Cancer Incidence and Outcome in Mutation-Positive and Mutation-Negative Family Members. JCO
27: 4793-4797
[Abstract][Full Text]
Nieminen, T. T., Gylling, A., Abdel-Rahman, W. M., Nuorva, K., Aarnio, M., Renkonen-Sinisalo, L., Jarvinen, H. J., Mecklin, J.-P., Butzow, R., Peltomaki, P.
(2009). Molecular Analysis of Endometrial Tumorigenesis: Importance of Complex Hyperplasia Regardless of Atypia. Clin. Cancer Res.
15: 5772-5783
[Abstract][Full Text]
Lynch, H. T., Lynch, J. F., Attard, T. A.
(2009). Diagnosis and management of hereditary colorectal cancer syndromes: Lynch syndrome as a model. CMAJ
181: 273-280
[Full Text]
Garg, K, Soslow, R A
(2009). Lynch syndrome (hereditary non-polyposis colorectal cancer) and endometrial carcinoma. J. Clin. Pathol.
62: 679-684
[Abstract][Full Text]
Lippman, S. M., Hawk, E. T.
(2009). Cancer Prevention: From 1727 to Milestones of the Past 100 Years. Cancer Res.
69: 5269-5284
[Abstract][Full Text]
Lippman, S. M.
(2009). Cancer Prevention Research: Back to the Future. Cancer Prevention Research
2: 503-513
[Full Text]
Pouchet, C. J., Wong, N., Chong, G., Sheehan, M. J., Schneider, G., Rosen-Sheidley, B., Foulkes, W., Tischkowitz, M.
(2009). A comparison of models used to predict MLH1, MSH2 and MSH6 mutation carriers. Ann Oncol
20: 681-688
[Abstract][Full Text]
Nilbert, M., Timshel, S., Bernstein, I., Larsen, K.
(2009). Role for Genetic Anticipation in Lynch Syndrome. JCO
27: 360-364
[Abstract][Full Text]
Hampel, H., Frankel, W. L., Martin, E., Arnold, M., Khanduja, K., Kuebler, P., Clendenning, M., Sotamaa, K., Prior, T., Westman, J. A., Panescu, J., Fix, D., Lockman, J., LaJeunesse, J., Comeras, I., de la Chapelle, A.
(2008). Feasibility of Screening for Lynch Syndrome Among Patients With Colorectal Cancer. JCO
26: 5783-5788
[Abstract][Full Text]
Balmana, J, Balaguer, F, Castellvi-Bel, S, Steyerberg, E W, Andreu, M, Llor, X, Jover, R, Castells, A, Syngal, S, for the Gastrointestinal Oncology Group of the Spa,
(2008). Comparison of predictive models, clinical criteria and molecular tumour screening for the identification of patients with Lynch syndrome in a population-based cohort of colorectal cancer patients. J. Med. Genet.
45: 557-563
[Abstract][Full Text]
Zhang, L.
(2008). Immunohistochemistry versus Microsatellite Instability Testing for Screening Colorectal Cancer Patients at Risk for Hereditary Nonpolyposis Colorectal Cancer Syndrome: Part II. The Utility of Microsatellite Instability Testing. J. Mol. Diagn.
10: 301-307
[Abstract][Full Text]
Clendenning, M., Baze, M. E., Sun, S., Walsh, K., Liyanarachchi, S., Fix, D., Schunemann, V., Comeras, I., Deacon, M., Lynch, J. F., Gong, G., Thomas, B. C., Thibodeau, S. N., Lynch, H. T., Hampel, H., de la Chapelle, A.
(2008). Origins and Prevalence of the American Founder Mutation of MSH2. Cancer Res.
68: 2145-2153
[Abstract][Full Text]
Walsh, M. D., Cummings, M. C., Buchanan, D. D., Dambacher, W. M., Arnold, S., McKeone, D., Byrnes, R., Barker, M. A., Leggett, B. A., Gattas, M., Jass, J. R., Spurdle, A. B., Young, J., Obermair, A.
(2008). Molecular, Pathologic, and Clinical Features of Early-Onset Endometrial Cancer: Identifying Presumptive Lynch Syndrome Patients. Clin. Cancer Res.
14: 1692-1700
[Abstract][Full Text]
Balmana, J., Steyerberg, E. W., Syngal, S.
(2008). Risk Quantification for Carrying Mutations in Lynch Syndrome Genes. Am Soc Clin Oncol Ed Book
2008: 59-64
[Abstract][Full Text]
Bakkum-Gamez, J. N., Gonzalez-Bosquet, J., Laack, N. N., Mariani, A., Dowdy, S. C.
(2008). Current Issues in the Management of Endometrial Cancer. Mayo Clin Proc.
83: 97-112
[Abstract][Full Text]
Schnipper, L. E.
(2007). Update in Oncology. ANN INTERN MED
147: 775-782
[Full Text]
Kauff, N. D.
(2007). How Should Women With Early-Onset Endometrial Cancer Be Evaluated for Lynch Syndrome?. JCO
25: 5143-5146
[Full Text]
Vasen, H F A, Moslein, G, Alonso, A, Bernstein, I, Bertario, L, Blanco, I, Burn, J, Capella, G, Engel, C, Frayling, I, Friedl, W, Hes, F J, Hodgson, S, Mecklin, J-P, Moller, P, Nagengast, F, Parc, Y, Renkonen-Sinisalo, L, Sampson, J R, Stormorken, A, Wijnen, J
(2007). Guidelines for the clinical management of Lynch syndrome (hereditary non-polyposis cancer). J. Med. Genet.
44: 353-362
[Abstract][Full Text]
Seiden, M. V., Patel, D., O'Neill, M. J., Oliva, E.
(2007). Case 13-2007 -- A 46-Year-Old Woman with Gynecologic and Intestinal Cancers. NEJM
356: 1760-1769
[Full Text]
Ganz, P. A.
(2006). Monitoring the Physical Health of Cancer Survivors: A Survivorship-Focused Medical History. JCO
24: 5105-5111
[Abstract][Full Text]
Guillem, J. G., Wood, W. C., Moley, J. F., Berchuck, A., Karlan, B. Y., Mutch, D. G., Gagel, R. F., Weitzel, J., Morrow, M., Weber, B. L., Giardiello, F., Rodriguez-Bigas, M. A., Church, J., Gruber, S., Offit, K.
(2006). ASCO/SSO Review of Current Role of Risk-Reducing Surgery in Common Hereditary Cancer Syndromes. JCO
24: 4642-4660
[Abstract][Full Text]
Chen, S., Wang, W., Lee, S., Nafa, K., Lee, J., Romans, K., Watson, P., Gruber, S. B., Euhus, D., Kinzler, K. W., Jass, J., Gallinger, S., Lindor, N. M., Casey, G., Ellis, N., Giardiello, F. M., Offit, K., Parmigiani, G., for the Colon Cancer Family Registry,
(2006). Prediction of germline mutations and cancer risk in the Lynch syndrome.. JAMA
296: 1479-1487
[Abstract][Full Text]
Lindor, N. M., Petersen, G. M., Hadley, D. W., Kinney, A. Y., Miesfeldt, S., Lu, K. H., Lynch, P., Burke, W., Press, N.
(2006). Recommendations for the care of individuals with an inherited predisposition to Lynch syndrome: a systematic review.. JAMA
296: 1507-1517
[Abstract][Full Text]
(2006). Lynch Syndrome: Reducing Gynecologic Cancer Risk. JWatch Women's Health
2006: 3-3
[Full Text]
(2006). Prophylactic Surgery Prevents Gynecologic Cancers in Women with Lynch Syndrome. JWatch Gastroenterology
2006: 9-9
[Full Text]
Offit, K., Kauff, N. D.
(2006). Reducing the Risk of Gynecologic Cancer in the Lynch Syndrome. NEJM
354: 293-295
[Full Text]